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ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
136 Binocularity / Preferred retinal loci
Sunday, May 03, 2015 1:30 PM–3:15 PM
Exhibit Hall Poster Session
Program #/Board # Range: 543–555/B0001–B0013
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Contributing Section(s): Low Vision, Visual Psychophysics/
Physiological Optics, Visual Neuroscience
Program Number: 543 Poster Board Number: B0001
Presentation Time: 1:30 PM–3:15 PM
Visual function and distribution of the preferred retinal loci in
patients with AMD
Eli Kisilevsky2, 1, Luminita Tarita-Nistor2, Esther G. Gonzalez2, 3,
Samuel Markowitz3, Mark Mandelcorn3, Michael H. Brent3, 2, Martin
J. Steinbach2, 3. 1School of Medicine, University of Toronto, Toronto,
ON, Canada; 2Vision Science Research Program, Toronto Western
Hospital, Toronto, ON, Canada; 3Department of Ophthalmology and
Vision Sciences, University of Toronto, Toronto, ON, Canada.
Purpose: Patients with AMD adapt to loss of central vision by
developing preferred retinal loci (PRLs) in the eccentric, functional
part of their retina. A PRL serves as a pseudo-fovea and is used in
performing visual tasks. PRLs typically occur close to the border of
the scotoma and most are in locations that correspond to the lower
and left visual fields (VFs). This is a retrospective, observational case
series study that examines whether visual acuity and ocular motor
control during fixation correlates with the PRL’s location in the VF
and whether the frequency distribution of the PRL locations differs
for the better-seeing (BE) and the worse-seeing (WE) eye.
Methods: A total of 137 eyes with AMD were included; based
on their acuity measures, 88 were BE and 49 were WE. Visual
acuity was measured at 6m. Fixation stability, PRL location, and
PRL distance from the former fovea were evaluated with the MP-1
microperimeter. Fixation stability was measured with a bivariate
contour ellipse area (BCEA). PRL location was categorized based on
5 areas in the VF: central, superior, inferior, left, and right.
Results: For the BE, the PRL frequency distribution was significantly
different for the 5 locations, χ2(4)= 19.9, p= .001. Most PRLs
occurred in the inferior (31%) and left (32%) VFs, and the least
in the right (7%) VF. Acuity and BCEA were best for PRLs in the
central and superior VF, but PRL distance from the former fovea
was smallest in these locations. Acuity and BCEA in the inferior VF
were similar to those in the left VFs. Acuity correlated with BCEA
and PRL eccentricity in the inferior VF [r(25)=0.51, p=0.007, and
r(25)=0.47, p=0.013, respectively] and left VF [r(26)=0.55, p=0.003,
and r(26)=0.40, p=0.033 respectively], but not in the superior or right
VF.
For the WE, the PRL frequency distribution was not different for
the 5 locations. Acuity correlated only with PRL eccentricity in
the inferior VF [r(9)=0.65, p=0.031]. No other relationships were
significant.
Conclusions: The PRL occurs most frequently in functional VFs that
are preferred for locomotion and left-to-right reading although a PRL
in the left VF is not adequate for reading. The relationship between
BCEA and acuity provides valuable information for rehabilitation,
but should be applied only for the BE.
Commercial Relationships: Eli Kisilevsky, None; Luminita
Tarita-Nistor, None; Esther G. Gonzalez, None; Samuel
Markowitz, None; Mark Mandelcorn, None; Michael H. Brent,
None; Martin J. Steinbach, None
Program Number: 544 Poster Board Number: B0002
Presentation Time: 1:30 PM–3:15 PM
Fixation stability as a function of viewing distance in patients
with AMD
Luminita Tarita-Nistor1, Esther G. Gonzalez1, 3, Taylor A. Brin1, Mark
Mandelcorn1, 3, Anne-Catherine Scherlen2, Martin J. Steinbach1,
3 1
. Vision Science Research Program, Toronto Western Hospital,
Toronto, ON, Canada; 2Essilor International, Paris, France;
3
Ophthalmology and Vision Sciences, University of Toronto, Toronto,
ON, Canada.
Purpose: People with normal vision perform activities of daily living
binocularly, while changing the viewing distance frequently and
effortlessly. Patients with AMD use preferred retinal loci (PRLs) from
the functional eccentric retina to perform visual tasks, but their ocular
motor control is impaired and this can affect visual performance.
In this study we examined how viewing distance affects fixation
stability during binocular viewing.
Methods: Ten patients with bilateral AMD participated. Visual acuity
at 6m was recorded with the ETDRS acuity test and monocular
PRL location was recorded with the MP-1 microperimeter. Each
patient’s better eye (BE) and worse eye (WE) were identified based
on their visual acuity. Fixation stability during binocular viewing was
recorded simultaneously for the two eyes with an eye-tracker at 3
viewing distances (40cm, 1m, 6m) in random order. At each viewing
distance, patients were asked to look at a 3deg cross and their eyemovements were recorded at 120 Hz for 15s. Fixation stability was
evaluated with a bivariate contour ellipse area.
Results: Mean binocular visual acuity was .42 ± .18 logMAR, that
of the BE was .42 ± .14 logMAR, and that of the WE was .83 ± .23
logMAR. Fixation stability during binocular viewing was analyzed
with a 3 (distance: 40cm, 1m, 6m) x 2 (eye: BE, WE) repeated
measures ANOVA. There was no effect of viewing distance on
fixation stability (p =.72). Fixation stability of BE and WE were not
different from each other (p=.80). There was no interaction effect (p
= .93).
Conclusions: Viewing distance does not affect fixation stability
during binocular viewing in patients with AMD. Fixation stability
data recorded during binocular viewing with an instrument with a
fixed viewing distance can be used in conjunction with visual tasks
performed at other viewing distances.
Commercial Relationships: Luminita Tarita-Nistor, None; Esther
G. Gonzalez, None; Taylor A. Brin, None; Mark Mandelcorn,
None; Anne-Catherine Scherlen, Essilor International (E); Martin
J. Steinbach, Essilor International (F)
Support: Essilor International
Program Number: 545 Poster Board Number: B0003
Presentation Time: 1:30 PM–3:15 PM
Preferred Retinal Loci and Fixation Stability in Patients with
Bilateral Ischemic Optic Neuropathy
Anuradha Mishra, Alexandra Selivanova, Mary Lou Jackson.
Ophthalmology, Harvard Medical School, Boston, MA.
Purpose: To determine if patients with a bilateral ischemic optic
neuropathy develop a preferred retinal locus (PRL) and asess their
fixation stability.
Methods: A retrospective review of 11 patients with bilateral
ischemic optic neuropathy, seen in Vision Rehabilitation clinic.
These patients underwent a history, ophthalmic examination and
SLO microperimetry (Optos). A suprathreshold strategy was used for
microperimetry testing and static fixation testing was performed with
the patient fixating on a cross for 5-20 seconds. A template was made
marking the fovea and disc margin in a healthy patient. This was
used to identify the approximate position of the fovea, and determine
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
if there was a PRL present. Fixation stability was assessed by two
methods. The first was the clinical classification proposed by Fujii
et al. (2002) which categorizes the dynamic fixation data captured
during microperimetery testing. Fixation is classified as being either
“stable”, “relatively unstable” or “unstable”. The second method was
using a 68% bivariate contour ellipse area (BCEA), which is based on
the static fixation data obtained when the patient fixates on a cross.
Results: There were 21 eyes included in the study. A no light
perception eye was excluded from the study as no microperimetry
data could be obtained. The mean age in this group was 63.9 years
of age (SD 10.8 years), and the mean visual acuity was logMar 0.70
(SD 0.55). The mean duration of disease was 17 months (SD 26
months). PRLs were found in 11/21 eyes (52%) and were bilateral
in 4/7 patients (57%). The odds of developing a PRL increased 1.51
times for every 0.1 unit increase in logMAR (p = 0.04) and decreased
by 2% for every 1 month increase in duration. By Fujii classification
10/21 (48%) of eyes had “stable” fixation and 11/21 (52%) had
“relatively unstable” fixation. The odds of a “relatively unstable”
Fujii classification increased 3.52 times (p= 0.09) for patients who
had a PRL compared to patients who did not have one. The mean
BCEA was 1.66 deg2 (SD 2.49 deg2) and there was no effect of the
presence of a PRL on the BCEA.
Conclusions: Patients with bilateral ischemic optic neuropathy can
develop a PRL and this is more likely to occur in eyes with a worse
visual acuity. There were no patients who were classified as having
“unstable” dynamic fixation and patients with a PRL were more
likely to have “relatively unstable” fixation.
Commercial Relationships: Anuradha Mishra, None; Alexandra
Selivanova, None; Mary Lou Jackson, None
Program Number: 546 Poster Board Number: B0004
Presentation Time: 1:30 PM–3:15 PM
Do patients with Stargardt maculopathy fixate eccentrically or
with their fovea when asked to look straight ahead?
Mary Lou Jackson1, Alexandra Selivanova1, William Seiple2, 3. 1MEEI,
Harvard Department of Ophthalmology, Boston, MA; 2Lighthouse
Guild, New York, NY; 3NYU School of Medicine, New York, NY.
Purpose: To assess if patients with Stargardt maculopathy change
fixation location when asked to look straight ahead during fixation
testing.
Methods: Patients diagnosed to have Stargardt maculopathy had two
5-second fixation tests using SLO-based macular perimeter. During
one test the patient was asked to,“Look at the cross” (LC). During
the second the patient was asked to, “Look straight ahead even if
you do not see the cross” (LS). Thirteen control subjects were tested
under the same conditions. Foveal location was determined with
OCT topographies scans in control subjects. The mean position of
anatomic fovea relative to the disk in controls was used to localize
the position of the fovea in Stargardt subjects. The mean vector
length, mean angle, and angular dispersion from anatomic fovea to
fixation for each subject under each condition were calculated. Data
about visual acuity, contrast sensitivity and time since diagnosis was
taken from the medical record.
Results: Records of 38 patients with Stargardt maculopathy were
reviewed. Fixation was most frequently in the superior retina (74%
LC condition and 67% LS condition). The average PRL eccentricity
was 11.02 degrees for the LC condition (median = 9.52 degrees)
and 7.84 degrees for the LS condition (median = 5.9 degrees). This
difference was statistically significant (P < 0.001). Sixty-nine percent
of subjects had inter-ocular PRLs that were < 10 degrees apart.
Approximately 43% of eyes did not statistically change fixation when
asked to look straight ahead. When fixation did shift, the magnitude
of the shift was correlated with the PRL eccentricity determined when
asked to look at the cross (OD, r = -0.69, P < 0.001; OS, r = -0.76,
P < 0.001; OU, r = -0.66, P < 0.001). The distance moved under the
different conditions (LC and LS) was not correlated with age, disease
duration, age of disease onset, visual acuity, contrast sensitivity or
BCEA.
Conclusions: Even after longstanding disease and established ability
to use eccentric fixation, some patients will move their fixation from
their preferred retinal locus (PRL) when asked to look in the direction
that they believe is straight ahead. Verbal directions can change
fixation in patients with Stargardt maculopathy and, therefore, may
impact measured visual function, such as visual acuity assessments or
PRL assessment.
Commercial Relationships: Mary Lou Jackson, None; Alexandra
Selivanova, None; William Seiple, None
Program Number: 547 Poster Board Number: B0005
Presentation Time: 1:30 PM–3:15 PM
Preferred retinal loci during binocular viewing at two viewing
distances
Esther G. Gonzalez1, 2, Luminita Tarita-Nistor1, Moshe Eizenman3,
2
, Mark Mandelcorn2, 1, Martin J. Steinbach1, 2. 1Vision Science
Research Program, Toronto Western Hospital, Toronto, ON, Canada;
2
Ophthalmology and Vision Sciences, University of Toronto, Toronto,
ON, Canada; 3Biomedical Engineering, University of Toronto,
Toronto, ON, Canada.
Purpose: To determine, in patients with AMD, whether the absolute
location of monocular and binocular PRLs changes as function
of viewing distance. The method presented here uses a remote
eye-tracking system that measures the optical axes of both eyes
without user calibration. This method yields the absolute location of
monocular and binocular PRLs which, until now, could only be done
monocularly.
We hypothesized that the locations of the binocular PRLs would not
change as a function of viewing distance.
Methods: Fifteen eyes from 8 patients with AMD fixated a 3 deg
cross for 15sec. The PRL location for the patients was recorded
monocularly with both the MP-1 microperimeter and the eye-tracking
system and then binocularly with the eye-tracking system. The eyetracker measured the horizontal and vertical components of angle
Kappa, which is the angle between the optical and the visual axis
(PRL for patients, fovea for controls) in each eye. Using the values of
10 control eyes, a transformation from the eye-tracking to the MP-1
coordinate systems was created to predict the absolute location of the
monocular and binocular PRLs in patients. Measurements were made
at two viewing distances: 70 cm and 6m.
Results: For the patients, the mean prediction errors for the
monocular PRLs (MP-1 - eye-tracker system) ranged from 0.03
to 1.05 deg. Viewing distance did not affect PRL location during
binocular viewing. For the 7 patients with complete data for the two
eyes, there were no consistent changes in PRL when viewing changed
from monocular to binocular as a function of viewing distance: 3
patients showed no appreciable changes in PRLs, 2 patients showed
larger changes at 70cm than at 6m and 2 patients showed the reverse.
For all patients, the PRLs of the better eye changed less than the
PRLs of the worse eye.
Conclusions: Binocular PRL location did not change as a function
of viewing distance. Changes in PRL location from monocular to
binocular viewing depended on the characteristics of the patients’
scotomas and not on the viewing distance. The absolute location
of the PRLs (i.e., relative to the optic disk) can be predicted with
acceptable accuracy with the method presented here.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Commercial Relationships: Esther G. Gonzalez, None; Luminita
Tarita-Nistor, None; Moshe Eizenman, ElMar Inc. (I); Mark
Mandelcorn, None; Martin J. Steinbach, None
Support: Supported by the Natural Sciences and Engineering
Research Council of Canada (NSERC) grant 130149 (ME); Vision
Science Research Program, Toronto Western Hospital; and an
anonymous donor.
Program Number: 548 Poster Board Number: B0006
Presentation Time: 1:30 PM–3:15 PM
Augmented reality eyewear for home-based vision training after
biofeedback rehabilitation of eccentric fixation
Marco U. Morales1, Paolo G. Limoli2, Celeste Limoli2. 1Ophthal
& Visual Sciences, Nottingham University, Nottingham, United
Kingdom; 2Centro Studi Ipovisione, Milano, Italy.
Purpose: Eccentric viewing training with microperimetry
biofeedback (MBF) is a rehabilitation technique aim to improve
fixation stability in patients with central scotoma and unstable
fixation. However home-based exercises under controlled
environment are difficult to implement due to the cost of technology.
The current pilot study explored the use of Augmented Reality
Eyewear (ARE) to perform eccentric viewing exercises on patients
with large central scotoma after MBF.
Methods: Fixation stability was measured in 10 patients with
bilateral central geographic atrophy. Patients performed a MAIA
microperimetry to evaluate the position of the preferred retinal locus
(PRL) and measure fixation stability. Secondly, all patients underwent
2 weekly MBF sessions during 2 weeks. In 5 patients, home-based
exercises were performed using the VIZUX eyewear (Rochester,
N.Y.) to perform vision exercises during 1 month, three times a week,
10 minutes per session. The ARE, connected to an iPad, showed 2
screens with a horizontal red line crossing the field of view. Such line
was positioned superiorly or inferiorly from the horizontal meridian
of the visual field corresponding to the PRL selected on the MAIA
during the MBF training. On the center of the screen, 2 different
targets were shown: a black dot, and a 5 letters word. Patients were
advised to move their gaze towards the horizontal line to attempt
fixation on the central target. The other 5 patients did not perform any
exercise during 1 month as a control group. All patients performed
a last MBF session to evaluate the consistency of fixation stability
outcomes. The MAIA P1 fixation stability index was used to evaluate
fixation performance.
Results: In the control group, the MAIA P1 fixation stability index
on the 5th MBF session showed a decrease of stability (mean = -13%)
when compared to the 4th MBF session. On the contrary the group
with ARE, showed the same, or slightly improved fixation stability on
the 5th MBF session (mean = +9.8%).
Conclusions: The results of this pilot study, suggest that augmented
reality eyewear with a dedicated home-based vision training
application, may help maintaining fixation stability outcomes
obtained during eccentric viewing training in vision centers with
microperimetry and biofeedback.
Commercial Relationships: Marco U. Morales, None; Paolo G.
Limoli, None; Celeste Limoli, None
Program Number: 549 Poster Board Number: B0007
Presentation Time: 1:30 PM–3:15 PM
Binocular Microperimetry with Simulated Asymmetric Bilateral
Scotomas
Emily K. Wiecek1, 2, Mary Lou Jackson3, Peter J. Bex2.
1
Ophthalmology, University College London, Boston, MA;
2
Psychology, Northeastern University, Boston, MA; 3Massachusetts
Eye and Ear Infirmary, Boston, MA.
Purpose: It is difficult to perform visual field testing on patients with
central field loss (CFL) because they may fixate with a Preferred
Retinal Location (PRL) in an unknown location outside the former
fovea. Microperimeters combine simultaneous imaging and testing
to measure the PRL location and CFL in retinal coordinates, but are
expensive and limited to monocular measurement. We develop and
evaluate a binocular microperimetry system that uses eye tracking
to track the optic nerve head (ONH) and stereo shutter glasses that
support simultaneous and independent presentation of stimuli to each
eye.
Methods: PRL location, and monocular and binocular
microperimetry were assessed in 6 normally sighted participants
with and without independent binocular simulated scotomas. The
simulated scotoma was presented as a 3° or 6° circular patch of pink
noise in a raised cosine window (λ=0.5°) to each eye monocularly
and required the participant to use a PRL to fixate a central cross. To
determine the location of the PRL and map stimulus presentation in
retinal coordinates, the ONH was mapped in each eye with kinetic
perimetry. The ONH location in each eye was compared with fundus
images offline and provided retinotopic references for monocular and
binocular microperimetry with Goldman III targets presented in a
polar 3-21 pattern.
Results: The ONH location in our system corresponded to its
location in fundus images and was an average location of 15.5°
temporal and 2° superior to fovea, across observers. The ONH
location mapped with asymmetric, binocularly-simulated scotomas
shifted vertically from the central cross an average of 6° (the size
of the larger scotoma) consistent with the use of a PRL in upper
visual field. The ONH location measured with a monocular scotoma,
however, corresponded to a shift the size of the independent
monocular scotoma, highlighting a difference in monocular and
binocular assessment of PRL location. Both binocular and monocular
perimetry accurately mapped the location and extent of the simulated
scotoma in all six participants after accounting for eye movements
with eye tracking data.
Conclusions: A computer-based binocular microperimetry system
can offer binocular assessment of CFL induced with simulated gazecontingent scotomas. This system can provide reliable information
about the binocular nature of visual field loss, fixation stability, and
PRL location in CFL patients.
Commercial Relationships: Emily K. Wiecek, None; Mary Lou
Jackson, None; Peter J. Bex, None
Support: R01EY021553
Program Number: 550 Poster Board Number: B0008
Presentation Time: 1:30 PM–3:15 PM
Fixational eye movements during binocular rivalry
Rajkumar Nallour Raveendran, William R. Bobier, Amy Chow, Raiju
J. Babu, Benjamin Thompson. School of Optometry and Vision
Science, University of Waterloo, Waterloo, ON, Canada.
Purpose: We have recently shown that the stability of fixational
eye movements (FEM) was decreased by suppression resulting
from strabismic amblyopia. To further investigate the impact of
suppression on fixation stability (FS), we measured FEM during
periods of binocular rivalry in normal individuals.
Methods: FEM were measured using an infrared video based
eyetracker at 500 Hz in 15 normal participants (age: 28±4 yrs).
Stimuli were sinusoidal gratings (3.6° diameter, 1.1cpd, central
fixation target 0.5° at 40cm). Binocular rivalry was created by
dichoptically presenting orthogonal gratings using a haploscope.
There were three control conditions: (1) grating to the left eye (LE)
and mean luminance to the right eye (RE) (monocular grating); (2)
identical gratings to both eyes dichoptically viewed through the
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
haploscope (dichoptic fusion); (3) binocular viewing of a single
grating without the haploscope (binocular fusion). Note that the
stimulus presented to the LE was the same in every condition
whereas the RE stimulus varied across conditions. Each trial took
40 seconds and grating orientation was varied every 4 seconds
to minimize adaptation in all conditions. There were 6 trials per
condition. Fixational stability (FS) was quantified using bivariate
contour ellipse area (BCEA).
Results: The effect of viewing condition (rivalry vs. control
conditions) differed significantly between the two eyes (p=0.003)
[Fig-1]. This effect involved a significant increase in LE FS for the
monocular condition compared to the rivalry condition (p=0.03).
However, the FS of the right eye did not differ in any of the dichoptic
conditions. Further, the FS in both eyes was significantly better for
the binocular fusion condition than the three dichoptic conditions
(p=0.0001).
Conclusions: We conclude that the FS in the fixing eye (LE)
was significantly improved when the fellow eye was suppressed
(monocular grating) compared to when the suppression was
alternating (binocular rivalry). Further we found that the stability
of FEM was improved with “normal” binocular fusion compared to
dichoptic fusion achieved through the haploscope.
Figure 1: Fixation stability (FS) across three dichoptic conditions and
normal binocular fusion. FS was quantified using bivariate contour
ellipse area (BCEA).
Commercial Relationships: Rajkumar Nallour Raveendran,
None; William R. Bobier, None; Amy Chow, None; Raiju J. Babu,
None; Benjamin Thompson, None
Support: NSERC-Canada to WRB
Program Number: 551 Poster Board Number: B0009
Presentation Time: 1:30 PM–3:15 PM
The relationship between ocular sensory dominance and
stereopsis
Ziming Liu1, 2, Hua Bi2, Bin Zhang2, Zuopao Zhuo3, 2, Qingxia Fan1,
Ling Xu1, Wei He1. 1Shenyang He Eye Hospital, Shenyang, China;
2
College of Optometry, Nova Southeastern University, Davie, FL;
3
Optometry, The Affiliated Eye Hospital of Wenzhou Medical
University, Wenzhou, China.
Purpose: Stereopsis is the highest form of binocular visual
processing, in which relative depth information is extracted from two
slightly different retinal images. During the process, the visual brain
receives and compares the signals sent from the two eyes. However,
the two eyes do not always have equal access to the visual brain. Just
as hand dominance, ocular dominance, the tendency to prefer visual
input from one eye to the other, also exists. It is not clear whether fine
stereopsis(lower stereothreshold and quicker response) would only be
found in persons with two balanced eyes. This hypothesis has never
been tested before because traditional methods to measure ocular
dominance were qualitative, which can only identify the dominant
eye without showing the degree of dominance. In this study, we set
to quantify the relationship between stereopsis and ocular sensory
dominance.
Methods: Thirty subjects participated in the study. For each
subject, ocular dominance was quantified with the continuous
flashing technique and ocular dominance index(ODI) was
computed. For stereopsis, the stereothresholds were measured with
5 viewing durations ranged from 25 to 400ms. The functions for
stereothresholds versus viewing durations were analyzed by an
empirical model of quadratic summation, in the form of th= Dmin(t2
+Tmin-2)0.5 where th is the stereothreshold at a given viewing
duration(t), Tmin is the constant that determines the horizontal
position of the function, which is related to the time at which the
stereothreshold becomes independent of duration(critical duration).
Dmin is the constant that determines the vertical position of the
function and is equal to the stereothreshold when t=Tmin.
Results: 60% of the subjects showed two relative balanced eyes(ODI
< 3db), 29% had moderate ocular dominance(3db≤ODI≤ 9db), and
approximately 11% showed strong ocular dominance(ODI> 9db).
For subjects with two relatively balanced eyes or moderate ocular
dominance, the Dmin values significantly lower than those with
strong ocular dominance. Also, the Tmin values were significantly
shorter in subjects with two relatively balanced eyes or moderate
ocular dominance.
Conclusions: People with two relatively balanced eyes tend to have
better stereopsis(small Dmin and short Tmin).
Commercial Relationships: Ziming Liu, None; Hua Bi, None; Bin
Zhang, None; Zuopao Zhuo, None; Qingxia Fan, None; Ling Xu,
None; Wei He, None
Support: Nova Southeastern University Health Professions Division
Grant
Program Number: 552 Poster Board Number: B0010
Presentation Time: 1:30 PM–3:15 PM
Objective Assessment of Eye Dominance
Kevin T. Willeford2, Kenneth J. Ciuffreda2, George A. Zikos1.
1
Manhattan Vision Associates, New York, NY; 2Biological and Vision
Sciences, SUNY State College of Optometry, New York, NY.
Purpose: The electrophysiological correlates of monocular defocus
during binocular viewing have yet to be explored with respect to
eye-dominance using the visual-evoked potential (VEP). Following
determination of both sensory and motor eye-dominance with
subjective clinical tests, a counterbalanced experimental design
was used to test the hypothesis that monocularly defocused dominant
eyes differentially affect the objective, pattern-VEP waveform as
compared to non-dominant eyes. Thus, the goal was to determine
whether one or both subjective tests of eye-dominance could predict
the binocular VEP waveform with a range of monocular defocus,
with application to monovision refractive correction.
Methods: The DiopsysTM NOVA-TR system was used to record the
pattern-VEP waveforms of 10 visually-normal, presbyopic, adult
subjects aged 50-70 yrs (x = 60). VEP amplitude and latency were
used as the outcome measures. First, eye dominance was assessed in
two ways: a sensory-based “sensitivity to blur task” and a motorbased “sighting task”. Next, while monocularly defocused, subjects
binocularly viewed a black-and-white checkerboard (20 min arc
check size, 74 cd/m2), pattern-reversal stimulus under 7 different test
conditions: baseline (full refractive correction), dominant (DE) eye
defocused +1 D, non-dominant (NDE) eye defocused +1 D, DE +2
D, NDE +2 D, DE +3 D, and NDE +3 D. Data were analyzed in twoways: first, each eye was classified as either “sensory dominant” or
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
“non-sensory dominant”, and second as either “motor dominant” or
“non-motor dominant”. Two one-way, repeated-measures ANOVAs
were used to investigate the effect of increasing monocular defocus
with both classifications.
Results: Under nearly all conditions (22/24=92%), the amplitude
and latency significantly decreased and increased, respectively,
from baseline with any amount of monocular defocus (p < 0.05).
Conversely, there was no difference in amplitude or latency between
the monocular defocus conditions themselves (p > 0.05). Moreover,
there were no significant differences revealed when comparing
defocused dominant vs. non-dominant eyes (p > 0.05): this was true
for both sensory and motor eye-dominance classifications.
Conclusions: Neither eye-dominance status (i.e., DE or NDE) nor
type (i.e., sensory or motor) provided a differential effect with respect
to the VEP findings. Thus, the VEP technique does not show promise
as an objective adjunct in the determination of eye-dominance.
Commercial Relationships: Kevin T. Willeford, None; Kenneth J.
Ciuffreda, None; George A. Zikos, None
Program Number: 553 Poster Board Number: B0011
Presentation Time: 1:30 PM–3:15 PM
Development of a binocular advantage for the performance of
complex manipulation skills in healthy children 5 to 13 years old
Fatimah A. Alramis1, Eric Roy1, Lisa Christian2, Ewa NiechwiejSzwedo1. 1Kinesiology, University of Waterloo, Waterloo, ON,
Canada; 2School of Optometry, University of Waterloo, Waterloo,
ON, Canada.
Purpose: Individual studies have shown that visuomotor
coordination and fine stereopsis continue to improve in normally
developing children from birth to early teenage years; however,
no study has systematically addressed the relationship between the
development of stereopsis and fine manipulation skills. Therefore, the
aim of this study is to examine the significance of binocular vision by
comparing monocular and binocular viewing in the performance of
complex manipulation tasks.
Methods: Seventy children (5-13 years old) with normal visual
acuity (0.0 logMAR) and stereoacuity (range: 25-100 arc sec) were
tested. Children performed 2 manipulation tasks: peg board and bead
threading under randomized viewing conditions (binocular, right
and left eye monocular). The main outcome measure was movement
time to complete the task. Binocular summation ratio was calculated
to determine the relative advantage in motor performance between
binocular and monocular viewing.
Results: Age and stereoacuity were significant predictors for
movement time during binocular viewing in the bead threading task
(R2=0.44), while age was the only significant predictor for movement
time in the peg board task (R2=0.46). The binocular summation ratio
for the bead threading task also indicated that older children relied
on binocular vision more than younger children (5-6 years old:
0.896; 7-8 years old: 0.879; 9-13 years old: 0.792). Results from the
multiple regression analysis for the bead threading task revealed a
7.3% variance in the binocular summation ratio was explained by
age and 3.6% was due to stereoacuity (p<0.05). In contrast, binocular
summation ratio was close to 1 for the peg board task and there was
no significant difference in movement time between binocular and
monocular viewing in children in different age groups (5-6 years
old: 1.086; 7-8 years old: 1.01; 9-13 years old: 0.944). Thus, fine
stereopsis is an independent predictor of performance on a complex
manipulation task; however, the extent of binocular advantage is
dependent on the task.
Conclusions: This research shows that 9-13 year-old children have
a greater binocular advantage during performance of a complex
manipulation task which requires precision grasping and object
placement. Thus, the bead threading task offers a more sensitive
assessment of the role of binocular vision in development of fine
manipulation skills.
Commercial Relationships: Fatimah A. Alramis, None; Eric Roy,
None; Lisa Christian, None; Ewa Niechwiej-Szwedo, None
Support: Saudi Arabian Cultural Bureau and University of Waterloo
Program Number: 554 Poster Board Number: B0012
Presentation Time: 1:30 PM–3:15 PM
Pitfalls in the Use of Stereopsis for the Diagnosis of Non-organic
Visual Loss
Kevin Sitko1, Jason Peragallo1, 2, Samuel Bidot1, Valerie Biousse1,
3
, Nancy J. Newman1, 4, Beau B. Bruce5, 6. 1Ophthalmology, Emory
University, Atlanta, GA; 2Pediatrics, Emory University, Atlanta,
GA; 3Neurology, Emory University, Atlanta, GA; 4Neurology and
Neurosurgery, Emory University, Atlanta, GA; 5Ophthalmology and
Neurology, Emory University, Atlanta, GA; 6Epidemiology, Emory
University, Atlanta, GA.
Purpose: Titmus stereoacuity testing is used to estimate visual
acuity (VA) in the diagnosis of non-organic visual loss (NOVL), but
only predicts mean VA and doesn’t account for normal inter-subject
variability. These predictions were derived from optical degradation
of VA in normal subjects and may not account for the variability
seen in patients with neuro-ophthalmic pathologies included in the
differential diagnosis of NOVL. The purpose of this study was to
evaluate the relationship between Titmus stereoacuity and minimal
visual acuity based on a real-world testing environment.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Methods: All patients presenting to our service between 4/25/2014
and 6/26/2014 underwent routine neuro-ophthalmic examination,
including Titmus stereoacuity measurements. A compound Bayesian
logit-lognormal model accounting for heteroskedasticity was used to
determine 95% and 99% prediction intervals of the worse eye’s near
visual acuity (VA) based on stereoacuity. LogMAR acuity and log
stereoacuity were analyzed.
Results: Of 561 patients, 28 were excluded for missing stereoacuity
or VA measurements, 4 for cognitive issues, 3 for suspected NOVL,
and 119 for heterotropia or history of strabismus/amblyopia. Patients
who correctly identified zero circles (43) were also excluded from
the calculation. 364 subjects were analyzed [median age: 45-yo
(range: 11-91); 258 (71%) women; median worse-eye VA 20/25;
median Titmus: 7 circles correct]. Titmus stereoacuity was positively
associated with VA: 9 circles correct (40 seconds of arc) indicated
VA of at least 20/41 with 95% confidence and 20/88 with 99%
confidence; 6 circles correct (80 seconds of arc): 20/63 and 20/197;
and 4 circles correct (140 seconds of arc): 20/106 and 20/582,
respectively.
Conclusions: When fully accounting for individual variation and the
full spectrum of neuro-ophthalmic diseases affecting VA, stereoacuity
remains associated with VA, but commonly-used VA estimates based
on stereoacuity overestimate VA. Our results more accurately predict
minimum VA from Titmus stereoacuity and should be preferentially
used when evaluating patients with suspected non-organic visual loss.
We demonstrate that Titmus stereoacuity cannot establish definitively
normal VA, and therefore can only suggest, but not establish, the
diagnosis of NOVL.
Commercial Relationships: Kevin Sitko, None; Jason Peragallo,
None; Samuel Bidot, None; Valerie Biousse, None; Nancy J.
Newman, None; Beau B. Bruce, None
Support: RPB; NIH/NEI core grant P30-EY006360; NIH/NEI K23EY019341
Program Number: 555 Poster Board Number: B0013
Presentation Time: 1:30 PM–3:15 PM
Stereroacuity in glaucoma patients
Chang Kyu Lee. Ophthalmology, Maryknoll Hospital, Busan, Korea
(the Republic of).
Purpose: In this study, we compared the near and distant stereo
acuity between glaucoma patients and normal group, analyzed the
near and distant stereoacuity according to the severity of glaucoma
and the type of visual field defect in the glaucoma patients.
Methods: 94 eyes in 47 patients with glaucoma and 80 eyes in 40
subjects (normal group) enrolled in cross-sectional study between
January 2014 and March 2014. Overall 87 subjects were tested
about near and distant stereoacuity and all glaucoma patients were
evaluated about visual field.
Results: There were statically significant differences in the mean
value of near and distant stereoacuity between glaucoma patients
and normal group (p=0.000, p=0.000), and the median of near and
distant stereoacuity in glaucoma patients showed higher value than
normal group. In HAP grading system, mean value and median
of near stereoacuity were increased proportionately to severity of
glaucoma (p=0.007), but distant stereoacuity showed no correlation
according to the severity of glaucoma (p=0.120). The near and
distant stereoacuity showed no differences between the subjects
with threat to fixation and the subjects with no threat to fixation
(p=0.005, p=0.980), but upward tendency of value of near steroacuity
appeared in the subjects with threat to fixation. Proportion of reduced
stereoacuity in near stereoacuiy was higher in glaucoma patients
in compared to normal group (76.2%, 45.5%). In comparison,
the proportion of absence of stereoacuity was higher in distant
stereoacuity in glaucoma patients comparing to normal group (61.9%,
0%).
Conclusions: Stereoacuity, both near and distant, was significantly
higher in glaucoma patients than normal group. In distance
stereoacuity test, the proportion of absence of stereoacuity was
remarkably high in glaucoma patients. In near stereoacuity test, the
more glaucomatous defect progressed, the poorer stereoacuity was
scored. But no correlation was detected in the distant stereoacuity.
The result that distant stereoacuity seriously deteriorated than the
near stereoacuity in glaucoma patient despite no correlation between
severity of glaucoma and distant stereoacuity can suggest that
distant stereoacuity may be considerably damaged in early stage of
glaucoma.
Commercial Relationships: Chang Kyu Lee, None
137 Extraocular muscles / Thyroid eye disease
Sunday, May 03, 2015 1:30 PM–3:15 PM
Exhibit Hall Poster Session
Program #/Board # Range: 556–572/B0014–B0030
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Contributing Section(s): Clinical/Epidemiologic Research
Program Number: 556 Poster Board Number: B0014
Presentation Time: 1:30 PM–3:15 PM
Novel Reverse Compressibility of Contracting Human Extraocular Muscles (EOMs) indicated By High Poisson Ratio (PR)
Lawrence H. Yoo, Robert A. Clark, Andrew Shin, Joseph L. Demer.
Ophthalmology, Jules Stein Eye Inst UCLA, Los Angeles, CA.
Purpose: A fundamental descriptor of the mechanical behavior of a
material is its PR, the ratio of transverse to axial strain, i.e., the ratio
of change in cross sectional area to change length during uniaxial
loading. A material having a PR <0.5 is said to be compressible.
Measurement of PR requires accurate 3-D determination of specimen
dimensions, typically by quantitative imaging during mechanical
loading. During passive, ex vivo tensile elongation, computed x-ray
tomography showed the PR of bovine EOM to be ~0.45 (Kim et al.,
BioMed. Res. International, 2013), but optical coherence tomography
demonstrated the PR of extraocular tendon to slightly exceed the
ideal incompressible value of 0.5 (Shin et al, ARVO, 2013). Since
the PR of contracting EOM is unknown, we used magnetic resonance
imaging (MRI) to determine the PR of all 4 rectus EOMs whose
axial dimensions change physiologically during horizontal & vertical
duction.
Methods: Surface coil MRI of 40 orbits of 20 normal adults was
performed at 312 micron resolution in ~20° target-controlled
horizontal and vertical eccentric gazes. Lengths were measured
in axial or quasi-sagittal images parallel to EOM long axes. Cross
sections were measured in quasi-coronal images perpendicular to
the long axes of each orbit. EOMs were outlined in coronal planes
to obtain area centroids cross sectional areas, and areal strain by
Green’s theorem. To correct for path curvature, centroids were
sequentially aligned to straighten each EOM for analysis. EOMs
were then discretized into elements 10-20 microns long. Changes in
longitudinal thickness of each element were determined to calculate
strain.
Results: Mean (±SD) PR values from discretized 3-D models for
the 20 superior, inferior, medial and lateral rectus muscles were
0.87±0.06, 0.79±0.03, 0.75±0.04 and 0.78±0.02 respectively.
Conclusions: PR values markedly exceeding the ideal compressible
value of 0.5 for contracting rectus EOMs imply that total volume
in the active contraction significantly exceeds that in relaxation, a
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
behavior termed reverse compressibility. Heretofore demonstrated
for tendons, reverse compressibility of EOMs would strongly impact
accuracy of finite element analysis simulations of EOM cooperative
biomechanics, and also provides a strong rationale for use of EOM
volume metrics as functional indices of contractility.
Commercial Relationships: Lawrence H. Yoo, None; Robert A.
Clark, None; Andrew Shin, None; Joseph L. Demer, None
Support: NIH EY08313
Program Number: 557 Poster Board Number: B0015
Presentation Time: 1:30 PM–3:15 PM
Comparison of myogenesis in human Extraocular muscle and
limb muscle in vitro
Hee-Young Choi1, Hye Shin Jeon1, Jeong Hyo Ahn1, Jin Hong
Shin2, Si Hyun Kim2. 1Ophthalmology, Pusan National University
hospital, Busan, Korea (the Republic of); 2Neurology, Pusan national
university Yangsan hospital, Yangsan, Korea (the Republic of).
Purpose: We investigated the myogenesis in human extraocular
muscle and compared with that in human limb muscle in vitro.
Methods: We obtained human extraocular muscle and limb muscle
during extraocular muscle surgery and limb muscle biopsy. Myoblast
was isolated and harvested until enough fraction of myoblast had
been achieved. Myogenesis was induced with F10 medium on
collagen-coated dish for 18 days. When myotube formation and
multiple nucleuses fusion were observed, cells were immunostained
with desmin (muscle specific protein) and myoD (determination of
the myogenic lineage) using each primary antibodies at day 10. We
evaluated morphologic characteristics of extraocular muscle and limb
muscle and compared extraocular muscle with limb muscle using
daily taken phase contrast photograph.
Results: Myoblasts fusion to form multinucleate myotube in both
human extraocular muscle and limb muscle primary culture started
at day 4. Immunocytochemistry for desmin and myoD were shown
positively stained at day 10 in both cells. Morphologic evaluation
revealed that extraocular muscle myoblasts were smaller and round
shape than limb muscle myoblasts at day 0. The process of myotube
formation and multinucleus fusion were similar time course in
extraocular muscle and limb muscle until day 7, but total area of
myotube formation and total number of nucleus in extraocular muscle
was smaller than limb muscle until day 10. However, total area of
myotube formation and total number of nucleus in limb muscle at day
2,4 was lower than day 10 (All, p<0.05) and total area of myotube
formation and total number of nucleus in extraocular muscle at day
3,5,7 was similar to day 10(All, p>0.05).
Conclusions: We have succeeded in primary culture of human
extraocular muscle myoblast and inducing myogenesis to form
multinucleated myotube in vitro. Our study reflects the differences
in myoblast and myogenesis between human extraocular muscle and
limb muscle
Commercial Relationships: Hee-Young Choi, None; Hye Shin
Jeon, None; Jeong Hyo Ahn, None; Jin Hong Shin, None; Si Hyun
Kim, None
Program Number: 558 Poster Board Number: B0016
Presentation Time: 1:30 PM–3:15 PM
Also Compartmentalized: Innervation of the Inferioir Oblique
(IO) Muscle in Primates
Alan Le1, 2, Vadims Poukens1, Joseph L. Demer1, 2. 1Ophthalmology,
University of California, Los Angeles, Los Angeles, CA;
2
Bioengineering, University of California, Los Angeles, Los Angeles,
CA.
Purpose: Innervation of the superior oblique muscle is separated into
minimally overlapping lateral and medial compartments in primates,
and superior and inferior compartments in non-primate mammalian
species. The horizontal rectus muscles are divided into superior and
inferior zones innervating non-overlapping sets of muscle fibers. We
explored the innervation pattern of the IO muscle and determined the
possibility of a compartmentalized model.
Methods: Whole orbits were obtained from two adult humans and
three rhesus monkeys. Each orbit was formalin fixed, embedded
in paraffin, coronally sectioned at 10 μm thickness, and stained
with Masson trichrome. In digital micrographs, oculomotor nerve
(CN3) branches were traced in serial sections using Photoshop
and reconstructed using ImageJ to create 3-D overlays of CN3
innervation in the IO muscle fibers.
Results: CN3 travels from the deep orbit and innervates at the
muscle belly of the IO. In both humans and monkeys, CN3 bifurcated
into two major branches prior to entering the IO muscle. Arborization
of the CN3 splits the IO muscle into two halves along its length.
One branch enters immediately as it reaches the muscle belly and
arborizes within muscle fibers from the posterior half. The other
branch straddles externally along the muscle belly before it penetrates
and arborizes in fibers of the anterior half.
Conclusions: Innervation of the IO muscle appears to follow a
compartmental model with the arborization dividing the muscle along
its length. Branching of the CN3 external to the muscle fibers allows
for independent movement between the two compartments. One
compartment could be more effective for elevation during adduction
while the other might have a greater effect on extorsion in primary
gaze.
Commercial Relationships: Alan Le, None; Vadims Poukens,
None; Joseph L. Demer, None
Support: NIH EY08313, Research to Prevent Blindness
Program Number: 559 Poster Board Number: B0017
Presentation Time: 1:30 PM–3:15 PM
Desmin in extraocular muscles
Fatima Pedrosa Domellof1, Kimmo Parkkonen1, Mona Lindström4,
Hanna Nord3, Jonas von Hoffsten3, Zhenlin Li2. 1Dept of Clinical
Sciences/Ophthalmology, UMEA University, Umea, Sweden;
2
UPMC Université Paris 6 - CNRS - INSERM, Institute of Biology
Paris-Seine, Paris, France; 3Umeå Centre for Molecular Medicine
(UCMM), Umea University, Umea, Sweden; 4Dept of Integrative
Medical Biology, Umea University, Umea, Sweden.
Purpose: To determine whether the lack of desmin reported in the
slow tonic muscle fibers of human extraocular muscles (EOMS) is
related to the presence of slow tonic myosin heavy chain (MyHC) or
multiple innervation or a feature specific to extraocular muscles and
to determine whether the EOMs are affected in a model of desmin
muscle dystrophy.
Methods: Immunohistochemistry was used to investigate the
presence of desmin in i) chicken anterior latissimus dorsi (ALD), a
muscle rich in slow tonic muscle fibers, ii) muscle spindles, whose
muscle fibers contain MyHC slow tonic and are multiply innervated
and iii) EOMs of rabbit, rat and zebra fish. The morphology, muscle
fiber size and muscle fiber integrity was evaluated in the EOMs of
desmin knockout mice and compared to that of wild type controls.
Results: Chicken ALD and muscle spindle fibers were labeled with
antibodies against desmin in similar patterns to those seen in control
skeletal muscle fibers. Muscle fibers containing slow tonic MyHC
in the EOMs of the different animals studied showed absence or
very low levels of expression of desmin, as previously observed in
the human EOMs. The EOMs of the desmin KO mice showed no
obvious signs of muscle dystrophy, in contrast to other highly used
skeletal muscles. More animals are under evaluation.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Conclusions: The very low levels of expression or lack of desmin
in the slow tonic muscle fibers was a feature typical for the EOMs
across species and not related to the presence of multiple innervation
or slow tonic MyHC, in other muscles. Preliminary data indicate that
the EOMs remain apparently unaffected in desmin muscle dystrophy.
Commercial Relationships: Fatima Pedrosa Domellof, None;
Kimmo Parkkonen, None; Mona Lindström, None; Hanna Nord,
None; Jonas von Hoffsten, None; Zhenlin Li, None
Support: Swedish Research Council (K2012-63x-20399-06-3),
County Council of Västerbotten (Cutting Edge Medical Research;
Central ALF), Stiftelsen Kronprinsessan Margaretas Arbetsnämnd för
Synskadade (KMA), The Kempe Foundation, The Swedish Society
of Medicine, The Medical Faculty, Umeå University
Program Number: 560 Poster Board Number: B0018
Presentation Time: 1:30 PM–3:15 PM
The Effect of Amniotic Membrane Grafting on healing and
wound strength in a Rabbit Model of Strabismus Surgery
Jeffrey B. Kennedy, Robert Enzenauer. Ophthalmology, University of
Colorado School of Medicine, Denver, CO.
Purpose: Postoperative scarring and adhesions after strabismus
surgery are common and may affect surgical outcomes. Amniotic
membrane grafts (AMG) have previously been shown to serve as
a successful platform for healing and to reduce scarring in cases
of ocular surface disease. Mixed results have been observed when
using AMG in conjunction with strabismus surgery. This study was
designed to evaluate the wound strength and histopathologic changes
on postoperative wound strength of amniotic membrane grafting in
conjunction with strabismus surgery using an in-vivo animal model.
Methods: Inferior rectus hang-back recession with processed
dehydrated amniotic membrane allograft (Ambiodry2, IOP Inc.,
Costa Mesa, CA) placed both between the sclera and the extraocular
muscle and between the extraocular muscle and the repositioned
conjunctiva was performed on 10 eyes of 10 New Zealand white
rabbits. Inferior rectus recession without amniotic membrane grafting
was performed on the alternate eye as a control. At postoperative
month 1, tensile strength of the muscle and overlying conjunctiva was
measured. Eyes were then enucleated and histopathologic analysis
performed to evaluate scarring and inflammatory response.
Results: Mean tensile strength of the AMG treated muscle and
conjunctiva was 441.4 +/- 274.4g and 640.3 +/-266.4g respectively.
The tensile strength of the control muscle and conjunctiva was
365.8 +/-199.8g and 595.2 +/- 315.3g respectively. No statistically
significant difference was detected based on ANOVA testing.
Histopathology demonstrated an increase in inflammatory infiltrate at
the muscle stump in AMG treated muscle.
Conclusions: There was no significant change in tensile strength
of the muscle insertion at post op month one in muscles treated
with amniotic membrane graft at the time of strabismus surgery.
Significant intra-animal variation in tensile strength was observed,
making a change difficult to detect. Further study is required to
determine the long term effect of amniotic membrane grafting on
post-operative scarring in strabismus surgery.
Commercial Relationships: Jeffrey B. Kennedy, None; Robert
Enzenauer, None
Program Number: 561 Poster Board Number: B0019
Presentation Time: 1:30 PM–3:15 PM
Growth factors regulate early events in adult zebrafish
extraocular muscle (EOM) regeneration
Alfonso Saera Vila, Alon Kahana. Ophthalmology and Visual
Sciences Department, University of Michigan, Ann Arbor, MI.
Purpose: Zebrafish are able to regenerate complex tissues, whereas
in mammals this ability is limited. Our laboratory uses EOMs as an
experimental model to study regeneration in sexually mature adult
zebrafish. Fibroblast growth factors (FGFs) have been shown to
promote tissue regeneration so we hypothesize that FGFs regulate
EOM regeneration in zebrafish.
Methods: A myectomy surgery that excised about 50% of the
lateral rectus (LR) muscle was performed to sexually mature adult
α-actin:EGFP zebrafish. At the end of the experiment, fish treated
with DMSO or the FGF receptor inhibitor SU5402 (17 μM) were
craniectomized and imaged. Muscle regeneration was calculated
using the uninjured contralateral muscle as a reference (100%).
Additionally, a-actin:EGFP or hsp70:dnfgfr1a-EGFP (a line that
expresses a dominant negative FGF receptor under control of the
heat shock protein 70 promoter) zebrafish were myectomized and
analyzed as described. Cell proliferation was analyzed injecting
fish with EdU to label cells in the S-phase of the cell cycle. The
involved cell signaling pathway was analyzed by testing the effect
of the MEK inhibitor U0126 (25 μM) in EOM regeneration and
proliferation as described. The activation of ERK was analyzed by
immunofluorescence and western blot.
Results: LR myectomy resulted in loss of abduction and, therefore,
the optokinetic response. Within 7 days, a new and functional LR
muscle regenerated. Both pharmacologic and genetic approaches
were used to analyze the role of FGFs. Treating myectomized fish
with the inhibitor SU5402 for 3 days reduced LR regeneration
from 70% to 58% (p<0.05). FGF role was confirmed using
hsp70:dnfgfr1a-EGFP in a time course experiment showing a
significant regeneration delay at 3 (13%, p<0.05), 5 (15%, p<0.05),
9 (36%, p<0.05), and 14 days (25%, p<0.01). Cell proliferation
was decreased in hsp70:dnfgfr1a-EGFP fish compared to WT fish
(19% and 27%, respectively; p<0.05). U0126 treated fish showed
a decrease in LR regeneration (71% vs 57%, p<0.05) and cell
proliferation (17% vs 9%, p<0.05). Immunofluorescence and western
blot confirmed the activation of ERK in the regenerating LR.
Conclusions: Our results show that FGFs, and most likely other
growth factors, play a significant role in the regeneration of EOMs in
zebrafish. Additional studies will be required to further uncover the
molecular mechanisms and target genes involved.
Commercial Relationships: Alfonso Saera Vila, None; Alon
Kahana, None
Support: NEI Grant R01EY022633
Program Number: 562 Poster Board Number: B0020
Presentation Time: 1:30 PM–3:15 PM
Medial rectus tendon elongation with bovine pericard
(Tutopatch®): an alternative to correct large horizontal squint
angles in graves’ orbitopathy
Monika Wipf. Augenklinik, Universitätsspital Basel, Basel,
Switzerland.
Purpose: Patients with Graves’ orbitopathy (GO) often present
large squint angles, especially following decompression surgery
of the medial orbital wall. These angles cannot be corrected with
conventional recession of the muscle alone. In this pilot study, we
report on four patients, where tendon elongation with Tutopatch®
was applied, to study the feasibility of this method, in particular the
dose- effect relationship.
Methods: We reviewed the charts of four patients with GO who
underwent bilateral recession of the medial rectus muscle and tendon
elongation with Tutopatch® within the last 5 years. At the time of
surgery, all patients had been stable for at least six months. Squint
angles were evaluated at distance and at near fixation preoperatively
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
as well as at postoperative week one, twelve and ≥52 (mean followup 49 months).
Results: Three patients had undergone previous orbital
decompression, one of whom had undergone previous bilateral 6mm
and 4.5mm, respectively, medial rectus recession with a residual
angle of 8°. The mean [range] preoperative angle was 38.8 [8- 68.7]°
at distance and 37.5 [6.9- 68.7]° at near fixation. This compared
to a mean postoperative angle of 1.1 [0- 2.9]° at distance and 5.1
[-2.0- 8.0]° at near fixation. Per muscle, the mean length of tendon
elongation was 6.8 [3.75- 13.5] mm with a mean total recession
of 9.8 [3.75- 17.5] mm. The mean dose- effect response was 1.83
[1.0-2.66] °/mm for the distance angle and 2 [1.4- 2.8] °/mm for the
near angle. All patients achieved a good functional outcome with
orthotropia, however in one patient following additional vertical
squint surgery.
Conclusions: We found the dose-effect response for medial rectus
recessions with Tutopatch® in GO to be comparable to reported
findings for dose-effect response for the inferior rectus muscle
recession with Tutopatch® (2°/mm), albeit with a slightly reduced
response at distance. This compares well to an effect of 1.99°/mm
for conventional inferior rectus recessions in GO as found in the
literature. However, in GO the dose-effect response for conventional
bilateral recessions of the medial rectus is considerably less (1.41.58°/mm).
Commercial Relationships: Monika Wipf, None
Program Number: 563 Poster Board Number: B0021
Presentation Time: 1:30 PM–3:15 PM
Clinical and Radiographic Features of Extraocular Muscle
Entrapment
Margaret L. Pfeiffer1, 2, Helen Merritt1, 2, Karina Richani1, 2, Margaret
E. Phillips1, 2. 1Ruiz Department of Ophthalmology and Visual
Science, The University of Texas Medical School at Houston,
Houston, TX; 2Robert Cizik Eye Clinic, Houston, TX.
Purpose: This is a retrospective chart review to investigate the
clinical and radiographic features of extraocular muscle entrapment
in patients presenting to the emergency department with orbital wall
fractures.
Methods: Patients who presented to the Memorial Hermann Hospital
emergency department, diagnosed with an acute orbital wall fracture
with extraocular muscle entrapment, and evaluated by ophthalmology
from January 2013 through November 2014 were included.
Clinical data were analyzed for the presence of symptoms and signs
associated with entrapment: diplopia, pain with eye movements,
nausea or vomiting, syncope, bradycardia, and restriction in
extraocular movements. Radiographic data were obtained including
interpretation of computed tomography (CT) by both ophthalmology
and radiology.
Results: Eight patients with an orbital wall fracture with extraocular
muscle entrapment confirmed by forced ductions were identified. The
median age was 22 (range: 9 to 72) years with 6 (75%) males and
4 (50%) white. Mechanisms of injury included 3 (37.5%) sportsrelated, 2 (25%) assault, 2 (25%) motor vehicle collision, and 1
(12.5%) fall. Diplopia and pain with eye movements were the most
common symptoms in 7 (87.5%) patients followed by nausea or
vomiting in 3 (37.5%). No patients had syncope. Two patients (25%)
were bradycardic with a pulse of less than 60 beats per minute; an
additional 2 had a pulse of 60. All had restricted extraocular motility.
Radiology accurately identified entrapment on CT in 3 (37.5%) cases
and interpreted an additional 3 (37.5%) as suspicious for entrapment.
Ophthalmology accurately identified entrapment on CT in 5 (62.5%)
cases and interpreted an additional 1 (12.5%) as suspicious. Overall,
ophthalmology correctly diagnosed entrapment in 5 (62.5%) cases
based on clinical and radiographic data. Three (37.5%) patients were
found to have entrapment on follow-up examination. In those patients
whose entrapment was not diagnosed, forced ductions were not
performed on initial evaluation.
Conclusions: Diplopia and pain with eye movements were the
most common symptoms of entrapment. Ophthalmology correctly
identified more cases of entrapment on CT than radiology, but 3 cases
were misdiagnosed by ophthalmology. We recommend high suspicion
for entrapment when both diplopia and pain with eye movements are
present and recommend performing forced ductions in all cases with
definite or suspicious imaging and clinical findings.
Commercial Relationships: Margaret L. Pfeiffer, None; Helen
Merritt, None; Karina Richani, None; Margaret E. Phillips, None
Support: National Eye Institute Vision Core Grant P30EY010608;
Challenge Grant from Research to Prevent Blindness; Hermann Eye
Fund
Program Number: 564 Poster Board Number: B0022
Presentation Time: 1:30 PM–3:15 PM
Quantitative Assessment of Ocular Motility Disturbance in
Orbital Blow-out Fractures
Jung Wook Lee1, EunHee Hong1, Moon sang won1, Heeyoon Cho1,
Sei yeul oh2, Yoon Duck Kim2, Han Woong Lim1. 1Ophthalmology,
Hanyang University Guri Hospital, Seoul, Korea (the Republic
of); 2Ophthalmology, Samsung Medical Center, Sungkyunkwan
University School of Medicine, Seoul, Korea (the Republic of).
Purpose: To measure the range of ocular motility using modified
limbus test (Fig 1) and to investigate the correlation with other factors
in patients with blow out fractures.
Methods: We enrolled 35 subjects with orbital blow-out fractures
who presented ocular motility disturbance. We measured the
maximum angle of ocular movements in the positions of restricted
motility of gaze using modified limbus test (Fig 2). We evaluated
number of points of contact of extraocular muscles to the fracture
edge (points of muscle contact) and the extent of blow out fracture
based on CT. The correlation between the degree of ocular motility
disturbance and the associated factors was estimated with linear
regression analysis.
Results: The mean of the angle of ocular motility disturbance
classified into grades 1,2,3, and 4 according to the clinical grage were
8.0±4.5°, 17.6±5.6°, 26.4±4.3°, and 40.2±8.3, respectively (P<0.001).
The angle of ocular motility disturbance showed significant
correlation with the clinical grading scale(R=0.730, P=0.015). The
extent of blow out fracture and the number of points of contact of
extraocular muscles to the fracture edge based on CT did not show
significant correlation with the angle of ocular motility disturbance
(R=0.250, P=0.127; R=0.453, P=0.072).
Conclusions: The modified limbus test using photographs in the
cardinal positions of gaze is an objective and reproducible tool
for quantifying ocular motility disturbance in the posttraumatic
evaluation of orbital blow-out fractures. The extent of blow out
fracture and number of points of contact of an extraocular muscle to
the fracture edge are not enough to predict posttraumatic limitation of
ocular movement in patients with blow out fractures in this study.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Figure 1. Image processing by Photoshop and Image J for quantitative
measurement of the ocular movement. A, Semitransparent image of
depression was overlapped with the primary position image using
Photoshop. B, The overlapping image was converted to identify the
margin of the limbus using Photoshop. C, Geometrical analysis with
Image J showing degrees of ocular rotation of the limbus.
Additional data providing specific guidelines for SEM surgeries will
make a strong impact on surgical planning and outcome. The purpose
of this study was to formulate a nomogram for SEM strabismus
surgery, rendering an effective reference and strategy.
Methods: This retrospective chart review (13 years, January 2000
- April 2013) is a single centre study approved by University of
British Columbia Research Ethics Board. We looked at the type of
strabismus and the initial type of surgery performed. The orthoptics
data pre- and post- SEM correction surgery was analyzed. We also
gathered intraoperative data showing the position of the SEMs and
the amount corrected. The primary analysis involved determination
of how much correction of alignment was achieved (in prism diopters
[PD]) per millimetre of the eye muscle corrected. Other data included
gender, age at the time of initial surgery, visual acuity, timing of SEM
at presentation (recent <6 weeks; distant >6 weeks), and pathology
results.
Results: Total of 70 patient [26 (37.1%) male, 44 (62.9%) female]
were included in the study. Twelve (17.1%) cases were recent
(<6 weeks) and 58 (82.8%) cases were distant (>6 weeks) events.
Pseudotendon was identified clinically and/or pathologically in 67
(95.7%) cases. Effect of muscle advancement for slipped muscles
ranged between 0.6 and 9.1 PD/mm. The average effect was 3.92 PD/
mm. The median effect was 3.76 PD/mm.
Conclusions: The effect of SEM advancement can be very powerful
but also unpredictable and variable. Other factors to consider in
assessing each patient and performing the surgery are the quality
of muscle and the tightness of the antagonists. It is also likely that
sensory suppression and fusion play a major role in the outcome,
particularly in the secondary strabismic patients. It is important
to remember management and outcome of SEM surgery are
multifactorial and surgeons must be aware of the variabilities for each
case.
Figure 2. An example of patient with blow-out fracture of right
inferior wall. Semitransparent image of elevation was overlapped
with the primary position image using Photoshop. The maximum
angle of elevation in right eye (the injured eye) was 22.6° which was
compared with 37.6° in left eye (the fellow eye).
Commercial Relationships: Jung Wook Lee, None; EunHee Hong,
None; Moon sang won, None; Heeyoon Cho, None; Sei yeul oh,
None; Yoon Duck Kim, None; Han Woong Lim, None
Program Number: 565 Poster Board Number: B0023
Presentation Time: 1:30 PM–3:15 PM
Retrieval of Slipped Muscles: Strategies and Impact
Ashley S. Ko1, Roy A. Cline2. 1Ophthalmology, University of Iowa,
Iowa City, IA; 2Ophthalmology, University of British Columbia,
Vancouver, BC, Canada.
Purpose: Slipped extraocular muscle (SEM) is an important and
serious complication of a strabismus surgery that is underdiagnosed,
often leading to intolerable symptoms and inappropriate reoperations
by misguided surgeons. Incidence and management data of SEM
is rare. While reference tables with projected corrective change per
millimeter of extraocular muscles correction with no previous surgery
is readily available, no such reference tables are available for SEMs.
Clinical appearance of slipped muscle seen intraoperatively.
Commercial Relationships: Ashley S. Ko, None; Roy A. Cline,
None
Program Number: 566 Poster Board Number: B0024
Presentation Time: 1:30 PM–3:15 PM
The role of the MRTFA-SRF pathway in fibroblast to adipocyte
transdifferentiation in thyroid eye disease
Lilani Abeywickrama. NHS, London, United Kingdom.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Purpose: Thyroid eye disease (TED) is a progressive autoimmune
disease in which orbital fibroblasts transdifferentiate into adipocytes
and extraocular muscles undergo fibrosis. Myocardin-related
transcription factor A (MRTFA) is a co-factor of the transcription
factor Serum Response Factor (SRF). MRTFA binds to cytoplasmic
G-actin and translocates to the nucleus, upon stimulation of actin
polymerization. The actin-MRTF-SRF circuit regulates the expression
of target genes responsible for regulation of the actin cytoskeleton.
The downregulation of MRTFA causes a decrease in SRF activation,
which facilitates the conversion of fibroblasts to adipocytes. We
hypothesize the two phenotypes, seen in TED, are associated with
the SRF-MRTFA pathway. Our study focuses on how diseased cells
differ from control cells in terms of their MRTFA content and how
this relates to their propensity to differentiate into adipocytes.
Methods: This project was divided into 3 sections: 1) Oil Red O
staining to examine for the presence of adipocytes in TED cells; 2)
Immunostaining for MRTFA and IGFR1 in diseased cells; and finally
3) Western Blot Analysis to determine whether levels of specific
proteins (MRTFA, IGFR-1) are present in samples of affected cells.
Results: Our results demonstrated that fibroblasts underwent
adipocyte differentiation in vitro. We found a significantly high
nuclear-cytoplasmic ratio in diseased cells that implied greater
baseline activity of SRF-MRTFA in affected OF and our final
experiment identified similar quantities of protein MRTFA in both
control and TED cells.
Conclusions: In conclusion, SRF-MRTFA is linked with the process
of adipogenesis and a dual pathway is involved in the pathology of
TED.
Commercial Relationships: Lilani Abeywickrama, None
Program Number: 567 Poster Board Number: B0025
Presentation Time: 1:30 PM–3:15 PM
Systemic and Immune Thyroid Status in Hispanic Patients with
Recently Diagnosed Thyroid Eye Disease at the Conde Valenciana
Institute of Ophthalmology – Mexico City. A 7 year review
Alberto Carlos Abdala Figuerola, Sharon Ball-Burstein, Angel
Nava-Castaneda, Gerardo Graue-Moreno. Oftalmologia, Instituto
Oftalmologia Fundacion Conde Valenciana, Mexico DF, Mexico.
Purpose: To determine primary systemic and immune thyroid status
in hispanic patients debuting with thyroid eye disease (TED).
Methods: Retrospective, descriptive, transversal and comparative
study.
Thyroid status based on TSH levels, antithyroglobulin (TG Ab)
and antithyroperoxidase (TPO Ab) levels and clinical activity score
(CAS) were recorded for each patient at their first visit. Other
relevant clinical and demographic data were obtained from the
clinical records.
Results: 60 patients (36 women and 24 men) were eligible for this
study. 28 patients (47%) were hyperthyroid (17 on inflammatory/
active phase and 11 non-inflammatory/non active), 28 (47%) were
euthyroid (20 on active phase and 8 non-active) and only 4 (6.6%)
were hypothyroid (1 active and 3 non-active) at presentation.
From the active phase patients (n= 38), 9 had positive TPO Ab (23%)
while 11 had negative TPO Ab (28%), 7 had positive TG Ab (18%)
and 13 had negative TG Ab (34%). From the non-active patients (n=
22), 3 had positive TPO Ab (13%), 4 had negative TPO Ab (18%), 5
had positive TG Ab (22%) and 3 had negative TG Ab (13%).
A Spearman correlation test showed no evidence of significant
correlation between TSH and antibodies levels regarding
inflammatory activity as evaluated using the CAS classification.
Conclusions: A distinctive, non previously reported distribution
regarding endocrine and immune status was found in Hispanic TED
patients, which reveals that as high as 47% of primary TED patients
were euthyroid at the time of diagnosis. Interestingly, no correlation
was found between active TED and the immune status of the patients
regarding TPO and TG antibodies. Prospective studies with larger
samples are warranted to confirm these findings.
Commercial Relationships: Alberto Carlos Abdala Figuerola,
None; Sharon Ball-Burstein, None; Angel Nava-Castaneda, None;
Gerardo Graue-Moreno, None
Program Number: 568 Poster Board Number: B0026
Presentation Time: 1:30 PM–3:15 PM
Thyroid-associated ophthalmopathy: Epidemiologic
characteristics in a reference institution in Mexico City.
Paulina Nunez, Juan Carlos Serna-Ojeda, Alberto Abdala Figuerola,
Osiris Olvera Morales. Instituto de Oftalmologia Conde de
Valenciana, Mexico City, Mexico.
Purpose: Describe the epidemiological characteristics in Mexican
population with thyroid-associated ophthalmopathy and a comparison
with other series reported in literature.
Methods: A descriptive, retrospective and observational study was
performed in the Thyroid Clinic of the Department of oculoplastic
and orbital surgery in a reference institution through the revision
of clinical records. Patients of any age and gender with confirmed
diagnosis of thyroid-associated orbitopathy were included. We
excluded patients with high myopia and other causes of proptosis,
incomplete files, or patients with a history of any ocular surgery
related to thyroid eye disease. The variables included in the study
were sex, age, smoking history, thyroid status, exophthalmometry
and presence of clinical signs like eyelid retraction at the time of first
consultation through a thyroid profile. A descriptive investigation
was performed for the variables according to its distribution and the
intergroup analysis was done with Student’s t test.
Results: A total of 241 patients, 187 (77.6%) females and 54
(22.4%) males were included. The 40 to 59 years interval was the
predominant group (56.4%) for the presentation of the disease. In
relation to smoking history, 42.3% of patients reported a positive
history for smoking. The thyroid status that predominated at the time
of diagnosis of thyroid-associated ophthalmopathy was euthyroidism
with 47.3%. The exophthalmometry had a media of 19.8mm. The
most common clinical sign was eyelid retraction in 83.4% of the
patients.
Conclusions: Variables such as age, sex and eyelid retraction
presented in similar proportions to those reported in studies
conducted in different countries and ethnic groups. In Mexican
population the initial thyroid hormone status is variable and patients
may present with eye manifestations despite of having a profile in
normal ranges.
Commercial Relationships: Paulina Nunez, None; Juan Carlos
Serna-Ojeda, None; Alberto Abdala Figuerola, None; Osiris
Olvera Morales, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 569 Poster Board Number: B0027
Presentation Time: 1:30 PM–3:15 PM
Effect of Orbital Decompression on Corneal Topography in
patients with thyroid ophthalmopathy
Su Ah Kim1, Kui Dong Kang2, Ji Sun Paik1, Su Kyung Jung1, Suk-Woo
Yang1. 1Ophthalmology, The Catholic University of Korea, Seoul St.
Mary’s Hospital, Seoul, Korea (the Republic of); 2Ophthalmology,
Incheon St. Mary’s Hospital, The Catholic University of Korea,
Incheon, Korea (the Republic of).
Purpose: This study was performed to evaluate the changes of
corneal astigmatism in patients undergoing orbital decompression
surgery.
Methods: This retrospective, nonrandomized comparative study
comprised 42 eyes from 21 patients with thyroid ophthalmolpathy
who underwent orbital decompression surgery between September
2011 and September 2014. The 42 eyes were divided into three
groups: control (9 eyes), two wall decompression (24 eyes), and
three wall decompression (8 eyes). Control was defined as the
contralateral eyes of 9 patients who underwent orbital decompression
surgery only in one eye. Corneal topography (Orbscan II), Hertel
exophthalmometry, and intraocular pressure were measured at 1
month before and 3 months after surgery. Corneal topographic
parameters analyzed were the total astigmatism(TA), steep axis(SA),
central corneal thickness(CCT), and anterior chamber depth(ACD).
Results: Exophthalmometry values and intraocular pressure were
significantly decreased after the decompression surgery. The change
(the absolute value (|x|) of the difference) of astigmatism at 3mm
zone was significantly different between the decompression group
and the control (P = .0250). There was also significant change of the
steepest axis at 3mm zone between the decompression group and the
control (P = .0331). An analysis of relevant changes in astigmatism
showed that there is a dominant tendency of incyclotorsion of the
steepest axis in eyes which underwent decompression surgery.
Using Astig PLOTTM, the mean surgically induced astigmatism
(SIA) was 0.21±0.88D with the axis of 46±22° which suggest that
decompression surgery did change the corneal shape and induced
incyclotorion of the steepest axis.
Conclusions: There is a significant change in corneal astigmatism
after orbital decompression surgery and this change is sufficient to
affect the optical function of the cornea. Surgeons and patients should
be aware of these changes.
Commercial Relationships: Su Ah Kim, None; Kui Dong Kang,
None; Ji Sun Paik, None; Su Kyung Jung, None; Suk-Woo Yang,
None
Program Number: 570 Poster Board Number: B0028
Presentation Time: 1:30 PM–3:15 PM
Surgical treatment of proptosis secondary to Thyroid Eye Disease
without a cutaneous incision
Paul Petrakos1, Benjamin M. Levine1, Ashutosh Kacker2, Aaron
Pearlman2, Gary J. Lelli1. 1Ophthalmology, Weill Cornell Medical
College, New York, NY; 2Otolaryngology, Weill Cornell Medical
College, New York, NY.
Purpose: To evaluate the improvement of proptosis secondary to
Thyroid Eye Disease in patients treated surgically without the use of
a cutaneous incision.
Methods: A retrospective study of 24 eyes of 13 patients who were
surgically treated for proptosis secondary to Thyroid Eye Disease
(TED) without the use of a cutaneous incision. Patients included
in the study underwent either (1) bony decompression (endoscopic
medial orbital wall and orbital floor decompression with removal
of bone with or without fat), or (2) orbital fat decompression. Pre-
operative and post-operative Hertel measurements, as well as patient
satisfaction, were documented to assess surgical outcomes.
Results:
The average pre-operative Hertel measurement for all eyes was
24mm (SD 3.75), 25mm (SD 4.96) for the bone decompression group
(n=8), and 23mm (SD 1.69) for the fat decompression group (n=8).
The average post-operative Hertel measurement for all eyes was
19.6mm (SD 1.08), 19.8mm (SD 1.39) for the bone decompression
group (n=8), and 19.4mm (SD 0.69) for the fat decompression group
(n=8). The mean post-operative improvement in Hertel measurement
for all patients regardless of surgical modality was 4.6mm (SD 3.03)
with a two-tailed p value <0.0001. For the eyes that underwent
bone decompression improvement was 5.3mm (SD 3.65), while fat
decompression was 3.9mm (SD 2.28). The difference in proptosis
between the two different surgical groups was not statistically
significant (p=0.373). Hertel pre and post-operative measurements
were not recorded for 8 patients. Subjectively all patients (100%)
reported satisfaction with their post-operative outcomes. No postoperative infections or inadequate decompression were seen in
any cases. One patient required subsequent strabismus surgery for
diplopia, but had a history of strabismus and patching as a child.
Conclusions: Orbital decompression with removal of bone or
orbital fat decompression without the use of a cutaneous incision
is an efficacious and safe modality for the treatment of proptosis in
TED patients. There was a statistically significant improvement in
proptosis for all patients treated surgically. The difference between
the two surgical groups was not statistically significant. Employing
this modality in aesthetically-minded patients who are concerned
over the potential for a cutaneous scar may be advantageous.
Commercial Relationships: Paul Petrakos, None; Benjamin M.
Levine, None; Ashutosh Kacker, None; Aaron Pearlman, None;
Gary J. Lelli, None
Program Number: 571 Poster Board Number: B0029
Presentation Time: 1:30 PM–3:15 PM
Comparative study of ganglion cell-inner plexiform layer
(GCIP) and circumpapillary retinal nerve fiber layer (cpRNFL)
measurements by spectral-domain optical coherence tomography
for the detection of dysthyroid optic neuropathy
Wai U IAO, Kam-lung, Kelvin K. Chong. The Chinese University of
Hong Kong, Hong Kong, Hong Kong.
Purpose: To compare ganglion cell-inner plexiform layer (GCIP) and
circumpapillary retinal nerve fiber layer (cpRNFL) measurements in
thyroid associated orbitopathy (TAO) eyes with no, suspected and
definite dysthyroid optic neuropathy (DON).
Methods: Retrospective, cross-sectional study. Thirty-four TAO
eyes, including 10 eyes with no DON, 7 with suspected DON and
17 with definite DON were analyzed. All subjects received complete
ophthalmic evaluation, visual field (VF) examination with the
Humphrey Visual Field Analyzer and optical coherence tomography
(OCT) imaging in the macular and circumpapillary regions with
Cirrus HD-OCT. Mann-Whitney U tests were used to compare GCIP
and cpRNFL thicknesses among the three groups with bootstrap
resampling with 10000 replications using one eye from each subject.
Results: The median GCIP thickness was 83.46 mm for the group
with no DON, 81.30 mm for the group with suspected DON, and
78.02 mm for the group with definite DON. Reduced GCIP thickness
was observed in the definite DON group (p < 0.017, after Bonferroni
adjustments) when compared with the groups with no or suspected
DON. The comparison of cpRNFL thickness among different groups
showed no significant differences.
Conclusions: In patients with TAO, GCIP thickness with SD-OCT is
a better objective test than cpRNFL for detection of optic neuropathy.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Commercial Relationships: Wai U IAO, None; Kam-lung, Kelvin
K. Chong, None
Program Number: 572 Poster Board Number: B0030
Presentation Time: 1:30 PM–3:15 PM
Outcomes of Surgical Management of Thyroid Eye Disease: A
Single-Centre Retrospective Study
Jia Quan Chaung1, 2, Raghuraj Hegde1, Shantha Amrith1, Inez Wong1,
Siew Shuen Chao1, Gangadhara Sundar1. 1Ophthalmology, National
University Hospital, Singapore, Singapore; 2National University of
Singapore, Singapore, Singapore.
Purpose: To study the outcomes of surgical management of thyroid
eye disease (TED) in a South East Asian Population
Methods: Retrospective single-centre case series of all TED patients
requiring surgery from Nov 2002 to August 2014 by 2 Oculoplastic
surgeons. Data recorded included demographic data, pre-operative
and post-operative visual acuity and exophthalmometry for orbital
decompression; ocular alignments, revision surgeries for both
strabismus and eyelid retraction.
Results: Of the 336 TED patients seen, 57 patients underwent
surgery, 24 male (42.1%) and 33 female (57.9%). Ethnicity: Chinese
(73.7%), Malay (14.0%), Indian (5.3%), Others (7.0%). Mean age
was 44.2 years (Range 2-81). Surgical indications: Eyelid retraction
(52.6%), proptosis (45.7%), cosmesis (33.3%), Exposure Keratopathy
(10.5%), Compressive optic neuropathy (8.8%). Surgical procedures
included orbital decompression (54.4%), eyelid surgery (52.6%)
and strabismus surgery (24.6%). 60 orbits of 31 patients were
decompressed: 2-wall (36.7%), pure fat (23.3%) 3-wall (21.7%),
1-wall (18.3%). Medial wall access – retrocaruncular (61.1%)
or endonasal (38.9%). Most 2-wall decompressions involved
balanced lateral and medial walls (72.7%). The mean reduction in
exophthalmometry was 4.5mm (Range -2 - 17) with an improvement
of at least one Snellen line in 62.9% of patients. Rate of induced
strabismus was 3.2%. Strabismus surgery was performed on 23 eyes
of 14 patients of which 1 required surgical revision. Medial rectus
was most frequently recessed (34.6%). Diplopia was resolved in
85.7%. Most eyelid surgeries involved the upper lid (55.1%) and
Muller’s muscle resection (69.7%). Mean reduction of MRD by
1.5mm. Satisfaction with appearance was achieved in 89.7% while
20.7% of eyelid surgeries required revision. Other eyelid procedures
performed included entropion surgery, permanent tarsorrhaphy,
epiblephron repair, ptosis repair and blepharoplasty.
Conclusions: Surgery for TED is not uncommon in our SouthEast Asian population. Orbital decompression was efficacious in
reducing proptosis and improving visual acuity. Complications
observed included diplopia and paresthesia. Strabismus and eyelid
surgery were used to effectively reduce diplopia and lid retraction
respectively. However, they may require revision surgeries to achieve
adequate correction.
Commercial Relationships: Jia Quan Chaung, None; Raghuraj
Hegde, None; Shantha Amrith, None; Inez Wong, None; Siew
Shuen Chao, None; Gangadhara Sundar, None
138 Pupil
Sunday, May 03, 2015 1:30 PM–3:15 PM
Exhibit Hall Poster Session
Program #/Board # Range: 573–586/B0031–B0044
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Program Number: 573 Poster Board Number: B0031
Presentation Time: 1:30 PM–3:15 PM
Divergent effects of rapid and slow photoreceptor degenerations
on the pupil light reflex of mice.
Stewart Thompson, Gabrielle Bui, Pratibha Singh, Xiu-Ying Liu,
Randy H. Kardon, Edwin M. Stone. Ophthalmology & Visual
Sciences, University of Iowa, Iowa City, IA.
Purpose: Pupillometry is increasingly being applied as a measure
of retinal function in the clinic and in laboratory studies of inherited
retinal disease. However, the pupil light reflex axis is complex
and the effects of diverse disease mechanisms and pathologies on
pupil function are poorly understood. The purpose of this study
was to determine how two distinct disorders of the rod and cone
photoreceptor cells affected the pupil response in mice.
Methods: We measured the pupillary light reflex in mice with
early and (rd1) and slow (Rd2P90) degeneration of the rod and cone
photoreceptor cells. At 90 days of age, Rd2 mice retain ~60% of
rods and cones, but these cells lack an outer segment making them
relatively insensitive to light. The effect of disease on the melanopsin
and rod/cone generated components of the pupil response were
assessed using 1-s red and blue, and 60-s blue stimuli at 0.01, 0.1, 1.0
and 10.0 μW.cm-2.
Results: Responses were severely reduced in rd1, having low
amplitude and no post-stimulus residual constriction even at the
highest irradiance. Remarkably, in Rd2P90 mice, responses were
only slightly reduced in compared to wild-type, with a deficit
more apparent to red than blue light. Indeed, there was no apparent
difference in post-stimulus residual constriction and steady state
responses at higher irradiances.
Conclusions: In rd1 mice, deficits in pupil responses largely track
deficits in rod/cone function: requiring 5-log units higher irradiance
to elicit responses to brief stimuli. However, the limited reduction
in sensitivity in Rd2P90 mice did not reflect the severity of the
structural or functional deficit in the rod and cone photoreceptor
cells. In our previous work, an unexpectedly high amplitude ERG
b-wave (12% of wild-type) pointed to an outer-retinal signal gain
mechanism. These pupillometry data suggest there may be additional
signal gain mechanisms acting on the pupil light reflex axis in slow
photoreceptor degeneration of Rd2P90 mice.
Commercial Relationships: Stewart Thompson, None; Gabrielle
Bui, None; Pratibha Singh, None; Xiu-Ying Liu, None; Randy H.
Kardon, None; Edwin M. Stone, None
Support: Stephen A. Wynn Institute for Vision Research
Program Number: 574 Poster Board Number: B0032
Presentation Time: 1:30 PM–3:15 PM
Characterization of the pupil responses to selective wavelength
(colored) light stimulation in Rhodopsin knockout (Rho-/-) mice
during retinal degeneration
Corinne Kostic1, Sylvain V Crippa1, Catherine Martin1, Randy H.
Kardon2, Yvan Arsenijevic1, Aki Kawasaki1. 1Dpt of Ophthalmology,
University of Lausanne, Jules-Gonin Eye Hospital, Lausanne,
Switzerland; 2Department of Ophthalmology and Visual Science,
University of Iowa, Iowa, IA.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Purpose: Pre-selected light stimuli were used to characterize the
pupillary light reflex (PLR) and monitor its modification during
retinal degeneration in the Rho-/- mouse model.
Methods: Wild type SV129 (n=6 to 9) and Rho-/- mice (n= 4 to
9, age 1 month to 6 months) were all tested following overnight
dark adaptation. An alternating, full-field red and blue light of
short duration (500 milliseconds) and of increasing intensity over
4 log-units was used to stimulate one eye. The pupil response of
the stimulated eye was recorded continuously using the A2000
Neuroptics system. The initial response during the first 2.5 seconds
(s) following the stimulus onset was described from maximal
contraction amplitude and the dynamics of immediate recovery from
this maximal contraction.
Results: Compared to wild type mice, one month-old Rho-/- mice
showed decreased maximal contraction amplitude to all blue
and red light stimuli except at the highest intensity blue stimulus
(2 loglux). With increasing age and progressive photoreceptor
degeneration, the amplitude of this maximal contraction and the
dynamic of the initial response are differently affected depending
on the intensity and wavelength of the stimuli. Following low and
intermediate red stimuli, the maximal contraction was reduced
drastically while contraction amplitude to high intensity red stimuli
remained relatively prserved. Following low blue stimulation, the
contraction amplitude is maintained despite the progression of the
photoreceptor degeneration. However, the early dynamic of the initial
response is modified with age with the loss of the characterized rapid
partial recovery observed with the first 2.5 s revealing the loss of
photoreceptor input to the initial response.
Conclusions: The Rho-/- model to study PLR responses provides
one model to study functional responses during the selective and
sequential loss of rods and cones. With progressive rod and cone
loss, the input of melanopsin photoreception to the pupil light
reflex proportionately increases and may be the only remaining
photosensitive cells at end-stage. The loss of photoreceptors during
degeneration in the Rho-/- model affects the PLR response to blue
light differently compared to red stimuli.
Commercial Relationships: Corinne Kostic, None; Sylvain V
Crippa, None; Catherine Martin, None; Randy H. Kardon, None;
Yvan Arsenijevic, None; Aki Kawasaki, None
Support: Provisu foundation
Program Number: 575 Poster Board Number: B0033
Presentation Time: 1:30 PM–3:15 PM
Chromatic pupillography in patients with Achromatopsia
Jolanta Lisowska1, 2, Lucasz Lisowski1, 2, Carina Kelbsch3, 2, Torsten
Strasser2, Ditta Zobor3, Helmut Wilhelm2, 3, Barbara Wilhelm2, Tobias
Peters2. 1Medical University of Bialystok, Bialystok, Poland; 2Pupil
Research Group at the Centre for Ophthalmology, University of
Tuebingen, Tuebingen, Germany; 3Department for ophthalmology,
University of Tuebingen, Tuebingen, Germany.
Purpose: The aim of the study was to characterize the function
of rods, cones and intrinsic photosensitive retinal ganglion cells
(ipRGCs) in patients with Achromatopsia by using a new, diseasespecific protocol for chromatic pupillography.
Methods: 4 Patients with Achromatopsia were tested after 10 min
light adaptation with stimulus duration of 4ms and 1s using shortwavelength (420nm; blue) and long-wavelength (605nm; red)
with stimulus intensities of 0,01 lux corneal illumination. Higher
illumination 28 lux was used for 1s short wavelength and longwavelength stimulus. The same stimulus conditions were repeated
after 20 min dark adaptation. For every stimulus the consensual pupil
response was recorded by using Compact Integrated Pupillography
(CIP by AMTech, Germany). Pupillary responses were compared
with 4 age- matched controls. Relative amplitudes (percent of initial
pupil diameter) of pupillary light reactions were evaluated as an
average of four reliable pupil traces.
Results: After light adaptation, the stimulation with 4ms and 1s
short-wavelength and long wavelength stimulus of 0,01 lux corneal
intensity did not show any responses either in Achromatopsia
patients or normal subjects. Compared to normal subjects, patients
with Achromatopsia showed a reduction of the pupil response to
1s short-wavelength and long-wavelength bright stimulus (28 lux)
in the light adapted state. In addition, after 1s short- wavelength
light stimulus (28 lux) in dark adapted state Achromatopsia patients
had smaller amplitudes compared to controls. Similar responses of
patients with Achromatopsia and normal subjects were obtained
after dark adaptation when using the long-wavelength stimuli of
28lux intensity. In contradiction, Achromatopsia patients showed
higher amplitudes than normal controls to 4ms, 1s short-wavelength
and long-wavelength light stimuli of 0,01 lux intensity in the dark
adapted state.
Conclusions: Pupil responses to chromatic stimuli indicate a
hypersensitivity of rod photoreceptors to low-intensity light
stimuli after 20 minutes dark adaptation (Achromatopsia patients
compared to controls). The presented stimulus protocol for chromatic
pupillography seems an easy applicable, non-invasive tool for the
diagnosis of Achromatopsia. As an objective and easy test method it
may be useful for clinical trials with novel interventions in order to
monitor treatment effects in Achromatopsia patients.
Commercial Relationships: Jolanta Lisowska, None; Lucasz
Lisowski, None; Carina Kelbsch, None; Torsten Strasser, None;
Ditta Zobor, None; Helmut Wilhelm, None; Barbara Wilhelm,
None; Tobias Peters, None
Support: Egon Schumacher-Stiftung, Germany
Program Number: 576 Poster Board Number: B0034
Presentation Time: 1:30 PM–3:15 PM
Study of the pupil light reflex in patients with Obstructive Sleep
Apnea
Gloria L. Duque-Chica1, 2, Carolina Gracitelli3, Ana Laura D.
Moura1, 3, Balázs V. Nagy1, 4, Geraldine de Melo3, Michel B. Cahali5,
Augusto Paranhos3, Dora F. Ventura1, 2. 1Instituto de Psicologia,
Universidade de São Paulo, São Paulo, Brazil; 2Núcleo de Apoio
à Pesquisa em Neurociência Aplicada (NAPNA), Universidade
de São Paulo, São Paulo, Brazil; 3Departamento de Oftalmologia,
Universidade Federal de São Paulo, São Paulo, Brazil; 4Department
of Mechatronics, Optics and Engineering Informatics, University
of Technology and Economics, Budapest, Hungary; 5Departamento
de Otorrinolaringologia do Hospital das Clínicas, Faculdade de
Medicina, Universidade de São Paulo, São Paulo, Brazil.
Purpose: To investigate the impact of obstructive sleep apnea
(OSA) on the vision of patients through the contribution of the
inner and outer retinae (melanopsin ganglion cells, cone and rod
photoreceptors, respectively) to the pupillary light reflex (PLR).
Methods: 56 eyes from 18 patients with OSA aging from 36-64 years
(mean age of 51.26 ± 7.84 years, 9 females) and 13 healthy control
participants aging from 39-74 years (mean age of 54.15 ± 9.59
years, 11 females) were studied. All were submitted to a complete
ophthalmological exam. OSA severity was quantified by the number
of apneas and hypopneas per hour during polysomnography using
the Apneas/hypopneas index (AHI) from moderate (15≤AHI<30, 17
eyes) to severe (AHI≥30, 15 eyes). PLR was measured with an eye
tracker (View Point, Arrington); stimuli were presented in a Ganzfeld
(Q450, Roland). Pupil responses were measured monocularly, to 1s
blue (470 nm) and red (630 nm) flashes with -3, -2, -1, 0, 1, 2, and
2.4 log cd/m2 luminances. The normalized peak amplitude (PA) of
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
the PLR and the amplitude of the sustained response (SR) at 6-8 s
(median value) after the light offset were measured. Mann-Whitney
U test was used for comparison among groups.
Results: The PA for blue stimuli was smaller for patients with severe
OSA compared to controls from -2 to 1 log cd/m2 (p<0.025). The red
PA was significantly (p<0.05) reduced in moderate and severe OSA
patients, respectively at 1 and 2 log cd/m2; and at -1, 1 and 2.4 log cd/
m2. Relative to controls, the SR for blue stimuli was smaller at -2 and
0 log cd/m2 in severe OSA (p<0.05).
Conclusions: To our knowledge, this is the first report using PLR
to investigate inner and outer retinal function in patients with OSA.
Patients with severe OSA had reduced rod and cone contributions to
the PLR. They also showed reduced melanopsin-driven responses
(but not statistically significant) compared to controls. In moderate
OSA only the cone response was reduced. Our data allow to conclude
that there is an association between number of apneas in OSA
patients and reduced contributions of the outer retinae to PLR.
Commercial Relationships: Gloria L. Duque-Chica, None;
Carolina Gracitelli, None; Ana Laura D. Moura, None; Balázs V.
Nagy, None; Geraldine de Melo, None; Michel B. Cahali, None;
Augusto Paranhos, None; Dora F. Ventura, None
Support: CAPES, FAPESP 2013/03553-0
Program Number: 577 Poster Board Number: B0035
Presentation Time: 1:30 PM–3:15 PM
Test–Retest Reliability of Hemifield, Central-field and Fullfield Chromatic Pupillometry For Assessing the Function of
Melanopsin-containing Retinal Ganglion Cells
Shaobo Lei3, Herbert C. Goltz2, 3, Manokaraananthan
Chandrakumar1, Agnes M. Wong1, 2. 1Ophthalmology and Vision
Sciences, The Hospital for Sick Children, Toronto, ON, Canada;
2
Ophthalmology and Vision Sciences, University of Toronto, Toronto,
ON, Canada; 3Program in Neurosciences and Mental Health, The
Hospital for Sick Children, Toronto, ON, Canada.
Purpose: The post-illumination pupil response (PIPR) is an index of
melanopsin-driven intrinsically photosensitive retinal ganglion cell
(ipRGC) activity. Hemifield analysis of PIPR may have important
clinical implications. We developed a novel method to induce PIPR
during hemifield stimulation and evaluated the test–retest reliability
of current methods of measuring PIPR under hemifield, central-field
and full-field stimulation.
Methods: Pupil response was recorded with an eye tracker in 10
visually normal subjects (6 females, mean age 30 years, range 1956). Light stimuli were presented using a Ganzfeld screen with a
custom built device to control the extent of retina being stimulated.
Blue light stimulation at 400 cd/m2 intensity was presented for 400
ms to the lower and upper halves of the central 30° (hemifields),
central 30° (central-field) and full-field to induce PIPR. Red fullfield stimulations at the same intensity and duration were also
presented as an internal control condition. Test-retest reliability
of the PIPR measures were assessed by calculating the intra-class
correlation coefficient (ICC) of 6 repetitions for lower and upper
hemifield stimulation, and 3 repetitions for central-field and full-full
stimulation.
Results: Hemifield, central-field and full-field blue light stimulation
induced increasingly greater PIPR in ascending order, while fullfield red light stimulation induced no PIPR. Mean lower and upper
hemifield PIPR were highly symmetric (Figure 1). Mean ICC of blue
light PIPR was 0.87 for lower/upper hemifield, 0.88 for central-field,
and 0.94 for full-field stimulation.
Conclusions: We described a convenient yet reliable method to
measure PIPR induced by hemifield, central-field and full-field light
stimulation. Good PIPR measurement reliability was obtained under
all viewing area conditions. This protocol will facilitate the clinical
applications of PIPR testing.
Figure 1: Mean pupil responses from 10 visually-normal subjects.
Pupil diameter data were normalized to baseline recording for 5 s
prior to the onset of blue or red light stimulation (400ms, 400cd/m2).
LHF, Lower Hemifield; UHF, Upper Hemifield; CF, Central-field;
and FF, full-field.
Commercial Relationships: Shaobo Lei, None; Herbert C. Goltz,
None; Manokaraananthan Chandrakumar, None; Agnes M.
Wong, None
Support: Supported by the Canada Foundation for Innovation, John
and Melinda Thompson Endowment Fund for Vision Neuroscience
Program Number: 578 Poster Board Number: B0036
Presentation Time: 1:30 PM–3:15 PM
Pupillary post-illumination response is dissociated from visual
function in OPA1 c.983A>G and c.2708_2711delTTAG autosomal
dominant optic atrophy
Claus Nissen, Cecilia Rönnbäck, Birgit Sander. Eye Department
Ø 37, Glostrup Hospital, University of Copenhagen, Glostrup,
Denmark.
Purpose: To examine whether the intrinsically photosensitive retinal
ganglion cells (ipRGCs) are preserved in genetically confirmed
autosomal dominat optic atrophy (ADOA).
Methods: 29 patients, aged 18 to 72 years, with either the c.983A>G
(n=14) or the c.2708_2711delTTAG mutation (n=15) were
examined with monochromatic pupillometry, using isoluminant
(300 cd/m2) red (660 nm) or blue (470 nm) light, optical coherence
tomography (OCT), automated visual field analysis (VFA), and
with determination of best corrected visual acuity (BCVA). Since
two different mutations were examined, initially we compared all
outcome variables between the two, and finding no statistically
significant difference (p> 0.05) between them, we pooled them and
compared this sample of 29 patients to an age matched control group
of 40 healthy controls
Results: BCVA was poor (56 letters ETDRS, compared with
91 letters in controls, p<0.0001, t-test) in the ADOA patients,
but their post-illuminatory pupil response (PIPR) did not differ
significantly from those of an age matched control group (blue light:
ADOA/controls = 1.04, p=0.45; red light: ADOA/controls = 1.06,
p=0.49, t-tests) and no statistically significant effect was noted of
peripapillary retinal nerve fiber layer thickness, ganglion cell-inner
plexiform layer thickness or age.
Conclusions: The pupillary light reflex (PLR) to blue light of 300
cd/m2 was preserved in both mutations despite severe visual loss
and optic nerve atrophy. The study confirms, in a large study of two
genetically homogeneous groups, that the intrinsically photosensitive
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
retinal ganglion cells (ipRGCs) are spared in ADOA, and that the
decline of their function with age is nonsignificant as compared with
that of a healthy control group.
Commercial Relationships: Claus Nissen, None; Cecilia
Rönnbäck, None; Birgit Sander, None
Program Number: 579 Poster Board Number: B0037
Presentation Time: 1:30 PM–3:15 PM
Chromatic multifocal pupillometer for objective perimetry
Ifat Sher-Rosenthal1, 2, Ron Chibel1, Soad H. Yahia1, Mohamad O.
Mahajna1, Daniel Ben-Ner1, Michael Belkin1, 2, Ygal Rotenstreich1,
2 1
. Goldschleger Eye Research Institute, Sheba Medical Center, Tel
Hashomer, Israel; 2Sackler Faculty of Medicine, Tel Aviv University,
Tel Aviv, Israel.
Purpose: We present infrared chromatic multifocal pupillometry
for objective perimetry and determination of retinal cell function in
healthy subjects and patients with macular and retinal degeneration.
Methods: A computerized infrared video pupillometer was used to
record pupillary responses to short- and long-wavelength stimuli
(peak 485 nm and 620 nm, respectively) presented by 76 LEDs,
1.8mm spot size, at increasing light intensities of 10-500 cd/m2 and
duration of 1 sec at different points of the 30 degree visual field.
Latency, amplitude, constriction velocity and re-dilation velocity
of pupillary responses were measured in 19 retinal and macular
dystrophy patients and 40 aged-matched controls.
Results: Comparison between control and retinal dystrophy patients
demonstrated statistically significant differences (p<0.05) in
amplitude and constriction velocity in vast majority (69) of locations
in response to short-wavelength stimuli and mostly in peripheral
targets in response to long-wavelength stimuli. Macular dystrophy
patients demonstrated significantly lower pupillary responses to long
wavelength stimuli in majority of the visual field and nearly normal
pupillary responses to short wavelength stimuli in majority (58) of
visual field locations. High consistency was observed in pupillary
responses recorded in serial testing (P<0.001, R=0.74 for longwavelength and P<0.001, R=0.683 for short-wavelength, n=870).
Conclusions: This study demonstrates the feasibility of using
pupillometer-based chromatic perimetry for objective assessment of
visual field defects. The device requires minimal patient cooperation
and demonstrates defects in rods or cones preferentially according to
the light stimuli.
Commercial Relationships: Ifat Sher-Rosenthal, None; Ron
Chibel, None; Soad H. Yahia, None; Mohamad O. Mahajna, None;
Daniel Ben-Ner, None; Michael Belkin, None; Ygal Rotenstreich,
Accutome Inc (F)
Support: Maratier Institute (TAU), Baharav grant (TAU), Accutome
Research Fund (USA)
Clinical Trial: NCT02014389
Program Number: 580 Poster Board Number: B0038
Presentation Time: 1:30 PM–3:15 PM
Color pupillography in Glaucoma and Ocular Hypertension - the
role of the intrinsically photosensitive retinal ganglion cells
Carina Kelbsch, Fumiatsu Maeda, Torsten Strasser, Tobias Peters,
Helmut Wilhelm, Barbara Wilhelm. University of Tübingen, Pupil
Research Group at the Centre for Ophthalmology, Tübingen,
Germany.
Purpose: Intrinsically photosensitive retinal ganglion cells (ipRGCs)
mediate the sustained post-illumination pupil response (PIPR)
following a visual stimulation with bright blue light. The purpose of
this study was to quantify this PIPR by means of color pupillography
in manifest glaucoma and ocular hypertension to find out how
ipRGCs are involved respectively and whether color pupillography
could be a useful tool for glaucoma diagnostics.
Methods: 25 patients with manifest glaucoma, 16 patients with
ocular hypertension and 16 healthy control subjects were examined
by stimulating one eye with either red (605nm) or blue (420nm)
colored light of 28 lx intensity and a stimulus duration of either 1s
or 4s. The consensual pupil light reaction was recorded by means
of infrared pupillometry over a period of 16 seconds. As primary
variable the post-illumination pupil response, PIPRblue-red, was
calculated and compared using t-test (Tukey-Kramer) for statistical
analysis.
Results: Using the 1s stimulus conditions we found significant
differences of the PIPRblue-red between glaucoma and normals
(p<0,001) and between glaucoma and ocular hypertension (p<0,007)
whereas there was no significant difference between ocular
hypertension and normals (p=0,9). However, when applying the 4s
stimulus conditions we could only identify significant differences
between glaucoma and normals if the PIPR was calculated starting
2s after stimulus offset. This may be explained by strong differences
in the dynamics (slope of the fitted line) of the pupillary responses
during the 4s red stimulus between the groups (p<0,001).
Conclusions: We demonstrated a significantly reduced PIPR in
manifest glaucoma that was consistent with the hypothesis of an early
impairment of the ipRGCs in glaucoma. Furthermore we observed
a pupillary escape during the 4s red stimulus in the glaucoma group
that cannot be fully explained so far but indicates an interaction of
ipRGCs and outer photoreceptors.
Commercial Relationships: Carina Kelbsch, None; Fumiatsu
Maeda, None; Torsten Strasser, None; Tobias Peters, None;
Helmut Wilhelm, None; Barbara Wilhelm, None
Support: Egon-Schumacher-Stiftung, Germany
Program Number: 581 Poster Board Number: B0039
Presentation Time: 1:30 PM–3:15 PM
Ocular determinants of pupillary light responses to red and blue
light: a population-based study
Sourabh Sharma1, Baskaran Mani1, Rukmini A. V2, Hla M. Htoon1,
Tin Aung1, Joshua Gooley2, Dan Milea1. 1Singapore Eye Research
Institute, Singapore, Singapore; 2Duke-NUS, Singapore, Singapore.
Purpose: The pupillary light reflex is assumed to be primarily
governed by neural responses to light. The aim of this study was
to explore the potential influence of ocular anatomical factors on
pupillary responses to light at different wavelengths and intensities,
using a novel pupillometer.
Methods: In this cross-sectional, population-based study, we
included 177 normal subjects (94.4% ethnic-Chinese, 65.5%
female), recruited from a general Polyclinic population. Direct
pupillary responses to continuously increasing irradiances (6.8 to
13.8 log photons cm-2 s-1) of red (631nm) and blue (469nm) light
were measured, using an infra-red pupillometer. Swept source
Optical Coherence Tomography performed in mesopic light allowed
measurement of lens vault (LV), anterior chamber width (ACW),
iris thickness (IT), iris volume and iris curvature (IC). Axial length
(AL), Anterior chamber depth (ACD) and lens thickness (LT) were
measured by noncontact partial coherence laser interferometry.
Univariate and multivariate regression analyses were performed to
determine ocular and systemic factors correlated associations with
pupillometry measurements.
Results: Pupil diameter measured in darkness was negatively
correlated with age (β = -0.334, p < 0.001). The amplitude (β =
-0.233, p = 0.006) and latency (β = 0.205, p = 0.014) of pupillary
constriction to blue light were associated with age. The iris thickness
was correlated with the amplitude of constriction to both blue (β =
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
-0.321, p < 0.001) and red light stimuli (β = -0.336, p < 0.001). Other
ocular parameters (LV, ACW, Iris volume, IC, AL, ACD, LT and
refractive errors) were not significantly associated with pupillometric
outcomes. The pupil responses to blue light were more invariable, as
compared to the red light, in terms of latency (p<0.001), amplitude
(p<0.001) and velocity (p<0.001) of constriction.
Conclusions: Pupillary responses to chromatic stimuli may be
affected by anterior segment parameters. Iris thickness seem to
affect pupillary responses to both blue and red light. Additional
colour pupillometric studies coupled with simultaneous anterior
segment video OCT recordings are needed in order to confirm these
preliminary results.
Commercial Relationships: Sourabh Sharma, None; Baskaran
Mani, None; Rukmini A. V, None; Hla M. Htoon, None; Tin Aung,
None; Joshua Gooley, None; Dan Milea, None
Support: Singapore National Eye Centre HREF Grant:
R1005/20/2013
Program Number: 582 Poster Board Number: B0040
Presentation Time: 1:30 PM–3:15 PM
Pupillary Response to Corneal Mechanical Stimulation.
Emmanuel B. Alabi, Varadharajan Jayakumar, Yunwei Feng, Trefford
L. Simpson. SCHOOL OF OPTOMETRY AND VISION SCIENCE,
UNIVERSITY OF WATERLOO, Waterloo, ON, Canada.
Purpose: Ocular somatosensory-autonomic reflexes play critical
roles in maintaining homeostasis of the eye. The purpose of this
study was to examine the pupil reflex before and after delivery of
nociceptive corneal mechanical stimuli.
Methods: Using a computerized Belmonte pneumatic esthesiometer,
mechanical stimuli from levels of detection threshold to twice (2x)
the threshold in 0.5x steps were delivered in random order to the
central cornea of 15 healthy subjects, aged 20 - 55 years. Threshold
was estimated using an ascending method of limits. Contralateral
pupil imaging was performed using a modified Logitech c920 digital
camera (Logitech c920; Logitech International S.A., Newark, CA) for
5 seconds before and after the stimulus. Consensual pupil sizes were
then measured (average of horizontal and vertical measures) using
ImageJ software (NIH, Bethesda, MD). Statistical analyses were
performed using Statistica 8.0 (StatSoft Inc., Tulsa, OK) and P ≤ 0.05
was considered statistically significant. Repeated-measures ANOVA
and post hoc Tukey HSD tests were used to examine the effect of
intensity on pupil size.
Results: The figures below show 8-bit processed images of the
contralateral pupil before and after delivery of the painful corneal
stimulus. The average pupil sizes were 5.82 ± 0.66mm (before
stimulus delivery), 6.41 ± 0.63mm (at threshold), 6.62 ± 0.65mm
(1.5x threshold) and 6.97mm ± 0.79 (2x threshold). Pupil sizes
increased with increasing stimulus intensity (P < 0.05) and the
maximum mechanical stimulus intensity induced the largest pupil
sizes (all P < 0.05).
Conclusions: Noxious, mechanical, central, corneal stimuli evoke
dose dependent sympathetic autonomic consensual pupillary dilation.
This study serves as a basis for the characterization of the local
stimulus-response neural circuitry relating nociceptive stimuli to
autonomic responses.
Commercial Relationships: Emmanuel B. Alabi, None;
Varadharajan Jayakumar, None; Yunwei Feng, None; Trefford L.
Simpson, None
Support: NSERC - Canada
Program Number: 583 Poster Board Number: B0041
Presentation Time: 1:30 PM–3:15 PM
A New Pupil Light Reflex Test for Detecting Optic Neuropathy
Independent of the Fellow Eye Which Highly Correlates to Visual
Field Volume
Pieter Poolman1, 2, Susan C. Anderson1, 2, Jade Grimm2, Jan M. Full1,
2
, Matthew Thurtell1, 2, Michael Wall1, 2, Randy H. Kardon1, 2. 1Iowa
City VA Health Care System, Iowa City, IA; 2Ophthalmology and
Visual Sciences, University of Iowa, Iowa City, IA.
Purpose: Our purpose was to develop and test a new paradigm for
detecting optic nerve disease in one eye, independent of the fellow
eye, so that patients with bilateral involvement can be diagnosed
and monitored using objective pupil responses. We also sought
to determine which stimulus light condition and pupil response
parameter (transient vs. sustained contraction) would provide the
greatest difference between normal and abnormal eyes and the
highest correlation with visual field sensitivity.
Methods: 39 patients seen in the neuro-ophthalmology clinic and
44 normal subjects were prospectively tested by computerized
pupillometry (NeurOptics DP2000, Irvine, CA) using a 1 second
red or blue light stimulus at 1 lux and 400 lux. The percent pupil
contraction from baseline pre-stimulus size was calculated for the
transient, initial response to the light stimulus and the sustained pupil
contraction at 6 seconds following offset of light. Visual fields were
obtained using standard kinetic Goldmann perimetry and the volume
of visual field sensitivity was determined and correlated with pupil
responses.
Results: We found the greatest statistically significant separation
between eyes of normal subjects vs. those with optic neuropathy
occurred with the transient pupil contraction using the 1 second,
400 lux blue light, compared to the sustained post-illumination
contraction. In response to 400 lux blue light, the transient
contraction gave the highest correlation with volume visual field
(r=0.85) compared to the sustained contraction (r=0.52).
Conclusions: The transient pupil contraction to bright blue light
provides an objective, easily recordable reflex, which correlates well
with visual field sensitivity. Under these stimulus conditions, both
photoreceptor input and direct activation of photosensitive retinal
ganglion cells summate the visual field input to the brain. This
approach provides a clinical tool for estimating visual dysfunction
that has important applications for remote diagnosis and monitoring
of vision threatening disorders.
Commercial Relationships: Pieter Poolman, None; Susan
C. Anderson, None; Jade Grimm, None; Jan M. Full, None;
Matthew Thurtell, None; Michael Wall, None; Randy H. Kardon,
Department of Veterans Affairs Research Foundation (S), Fight for
Sight (S), Novartis (F)
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Support: C9251-C: Department of Veterans Affairs Rehabilitation
Research and Development Division, Iowa City VA Center for the
Prevention and Treatment of Visual Loss; W81XWH-10-1-0736:
Department of Defense, TATRC
Program Number: 584 Poster Board Number: B0042
Presentation Time: 1:30 PM–3:15 PM
Blue and red light-evoked pupil responses in photophobic
individuals with traumatic brain injury
Andrew T. Hartwick, Phillip Yuhas, Patrick Shorter, Catherine
McDaniel, Michael Earley. Optometry, Ohio State University,
Columbus, OH.
Purpose: Photophobia is a common symptom in individuals who
have suffered a traumatic brain injury (TBI). Recent evidence has
implicated blue light-sensitive intrinsically photosensitive retinal
ganglion cells (ipRGCs) in contributing to the neural circuitry
mediating photophobia in migraineurs. The goal of this work is to
test the hypothesis that ipRGC function is altered in TBI patients with
photophobia by assessing relative pupillary responses to blue and red
light.
Methods: Data was collected from 22 case subjects (mean age
= 43.3±2.4; 59% female) with a prior TBI and self-reported
photophobia, along with 12 control subjects (mean age = 42.6±4.5;
58% female). After a 10 min dark adaptation period, light stimuli
were generated by blue (470 nm, 1x1013 phots/s/cm2) and red (625
nm, 7x1013 phots/s/cm2) LEDs. Each stimulus flashed on and off at
0.1 Hz for 30s and was delivered to the dilated left eye while the right
pupil was recorded. The amplitude of normalized pupil fluctuation
was quantified using Fourier fast transforms.
Results: As ipRGCs continue to fire after light offset, smaller values
of the Fourier-derived pupil fluctuation are indicative of greater
ipRGC contribution to the pupil responses. In either the case or the
control group, the Fourier-derived pupil fluctuation was significantly
(P<0.05) less for the blue (25.4±6.6 [SD], 23.8±2.4) versus red light
(28.4±5.6, 28.1±3.1), consistent with the greater contribution of
ipRGCs to the former stimulus. As evident in the standard deviation
of the fourier-derived data, case subjects displayed greater variability
in their pupil responses, especially to blue stimuli. On a 5-point
scale, the case subjects rated the first blue pulse to be significantly
brighter (4.3±0.1) than the second (4.0±0.2) or third pulses (3.7±0.2),
and these subjective brightness grades were significantly higher that
obtained from the controls for the same stimuli.
Conclusions: Similar to control subjects, case subjects showed
robust ipRGC-mediated components in their pupil responses to
blue light. The mean Fourier-derived amplitude of pupil fluctuation
evoked by flashing blue stimuli did not differ between the two subject
groups. However, greater pupil response variability in the case
subjects suggests that ipRGC function may be more heterogeneous in
this group. Subjectively, the case subjects reported the stimuli to be
brighter than that reported by the control subjects.
Commercial Relationships: Andrew T. Hartwick, None; Phillip
Yuhas, None; Patrick Shorter, None; Catherine McDaniel, None;
Michael Earley, None
Support: DoD grant W81XWH-12-1-0434
Clinical Trial: NCT01942564
Program Number: 585 Poster Board Number: B0043
Presentation Time: 1:30 PM–3:15 PM
The Effect of Age and Refractive Error on Pupil Size
Kathryn Dumbleton1, Michel Guillon1, 3, Panagiotis Theodoratos1,
C. Benjamin Wooley2, Kurt Moody2. 1OCULAR TECHNOLOGY
GROUP - International, Berkeley, CA; 2Johnson & Johnson Vision
Care Inc., Jacksonville, FL; 3School of Life and Health Sciences,
Aston University, Birmingham, United Kingdom.
Purpose: The size of the pupil plays a critical part in controlling
the performance of all vision correction modalities incorporating a
presbyopic correction, including contact lenses, refractive surgery
and intraocular lenses. While the effect of luminance, the dominant
factor affecting pupil size, is well known, little information is
available regarding other contributing factors such as aging and
refractive status.
Methods: Three hundred and four patients (127 Male, 177 Female)
aged 18 to 78 year made up the cohort population in this study. The
non-interventional investigation involved a single visit to the OTG-i
clinic. The pupil size was measured at three controlled luminance
levels 250cd/m2 (daytime), 50cd/m2 (indoor lighting) and 2.5cd/m2
(night driving).
Results: The results obtained showed that: (i) Pupil size decreases
with age, the effect being most marked at low luminance. At 250cd/
m2 means: 18-39 yrs = 2.8mm, 40-54 yrs = 2.67mm, 55+yrs =
2.56mm (p=0.046). At 50cd/m2 means: 18-39 yrs = 3.68mm, 40-54
yrs = 3.37mm, 55+yrs = 3.21mm (p<0.001). At 2.5cd/m2 means: 1839 yrs = 6.15mm, 40-54yrs = 5.49mm, 55+yrs = 4.99mm (p<0.001).
(ii) Pupil size at low luminance is significantly greater for myopes
(high myopes mean = 5.98mm; low myopes mean = 5.91mm) than
hyperopes (mean = 5.15mm) (p =0.020). (iii) Pupil size changes
modelled by multi linear regression (p<0.001) identified age
(p<0.001) and refractive error (p=0.019) as significant factors at low
luminance.
Conclusions: The study demonstrates that both age and refractive
status affect pupil size with larger pupils measured for younger
patients and myopes. The implications for the design of multifocal
corrections are that the design should take into consideration both
the age (faster progression for higher near additions) and refractive
power (faster progression for hyperopic corrections).
Commercial Relationships: Kathryn Dumbleton, Alcon Inc. (R),
Johnson & Johnson Vision Care Inc. (C), Johnson & Johnson Vision
Care Inc. (F), Johnson & Johnson Vision Care Inc. (R); Michel
Guillon, Alcon Inc. (R), Johnson & Johnson Vision Care Inc. (C),
Johnson & Johnson Vision Care Inc. (F), Johnson & Johnson Vision
Care Inc. (R); Panagiotis Theodoratos, Johnson & Johnson Vision
Care Inc. (F); C. Benjamin Wooley, Johnson & Johnson Vision Care
Inc. (E); Kurt Moody, Johnson & Johnson Vision Care Inc. (E)
Support: This study was funded by Johnson & Johnson Vision Care
Inc.
Program Number: 586 Poster Board Number: B0044
Presentation Time: 1:30 PM–3:15 PM
The degree of anisocoria in pediatric patients with Horner
syndrome when compared to children without disease
Christy Benson1, Sarah Suh2, Donny W. Suh1, 2. 1Ophthalmology,
Truhlsen Eye Institute, University of Nebraska Medical Center,
Omaha, NE; 2Ophthalmology, Children’s Hospital and Medical
Center, Omaha, NE.
Purpose: To study the magnitude of anisocoria in pediatric patients
using the plusoptiX A08 photoscreener as compared to pediatric
patients with Horner syndrome to determine if anisocoria alone
should raise suspicion for the diagnosis.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Methods: The medical records of 592 consecutive patients, neonates
to nine years of age, were collected and analyzed. All patients had
complete ophthalmologic examinations that included photoscreening
with the plusoptiX A08. Data included age, pupil sizes, and degree
of anisocoria. This was then compared with pupillary sizes of 32
pediatric patients with a known diagnosis of Horner syndrome.
Results: Of the 592 children without Horner syndrome, 404 had
anisocoria of ≤0.5 mm (68.13%), 167 had anisocoria of 0.6-1.2 mm
(28.16%), and 21 had anisocoria of >1.3 mm (3.70%). There was
no correlation between increasing age and severity of anisocoria
(p=0.55). The average degree of anisocoria was 0.5 mm. For pediatric
patients with a diagnosis of Horner syndrome, the average level of
anisocoria in room light was 1.37 mm and 2.0 mm in darkness. In
room light, 3 children had anisocoria of ≤0.5 mm (9.4%), 14 had
anisocoria of 0.6-1.2 mm (43.8%), and 15 had anisocoria of >1.3 mm
(46.9%). In darkness, the level of anisocoria increased in 19 patients,
causing the first category, ≤0.5 mm, to include 1 child (3.1%), the
second group to include 5 patients (15.6%), and the last group to
include 26 patients (81.3%). Of the 32 Horner syndrome cases
reviewed, ptosis was present in 100% of cases. Other associated signs
included heterochromia (28.1%), anhidrosis (9.4%), straight hair on
affected side/curly unaffected (9.4%), neck mass (6.3%). In 37.5%
of cases, imaging results were negative and no specific etiology was
determined
Conclusions: In a study of 592 children without Horner syndrome,
pupillary size was found to increase with age, while the degree of
anisocoria remained stable in both light and dark. About half of
the pediatric population studied had anisocoria of up to 0.5 mm.
In children with a diagnosis of Horner syndrome, the majority had
anisocoria ≥1.3 mm, with the discrepancy in pupil size becoming
more apparent in levels of low light intensity. The level of anisocoria
increased in the dark in 19 of 32 Horner syndrome cases reviewed
(59.3%), with an average increase of 0.57 mm. In this study,
anisocoria greater than 1.3 mm was rarely found to be physiologic
(3.4%).
Commercial Relationships: Christy Benson, None; Sarah Suh,
None; Donny W. Suh, None
212 Strabismus, I
Monday, May 04, 2015 8:30 AM–10:15 AM
4CD Mile High Blrm Paper Session
Program #/Board # Range: 1327–1333
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Program Number: 1327
Presentation Time: 8:30 AM–8:45 AM
Reliability of dichotomizing strabismus outcome by diplopia
descriptors
Jonathan M. Holmes, David A. Leske, Sarah R. Hatt. Ophthalmology,
Mayo Clinic, Rochester, MN.
Purpose: We previously developed a Diplopia Questionnaire
capturing frequency of diplopia on a 5-point Likert scale (always,
often, sometimes, rarely and never) in specific gaze positions
(reading, distance straight ahead, right, left, up, down), to incorporate
patient reported symptoms into outcome assessment for strabismus.
For some analyses of diplopia, we have proposed defining “success”
as “never or rarely” in distance straight ahead and reading positions.
We investigated the test-retest reliability of such a classification.
Methods: 64 adults (18 to 87 years old) with stable strabismus and
no intervention within the previous 6 months, completed the Diplopia
Questionnaire at a clinic visit and at least 5 days later (5 to 154
days), 30 (47%) by mail and 34 (53%) at a return visit. Strabismus
types included childhood, neurologic and mechanical and no change
in treatment was allowed between test and retest. For analysis we
categorized patients by defining “success” as “never or rarely”
in distance straight ahead and reading positions. Agreement was
assessed by calculating kappa values and frequencies.
Results: At the first exam, 20 (31%) would have been classified as
success, and 19 (30%) at the second exam. Even though agreement
would have been designated “substantial” with a kappa of 0.74 (95%
CI 0.56 to 0.92), 4 patients (6%, 95% CI 2% to 15%) would have
been classified as success on the first exam but not on the second,
and 3 (5%), 95% CI 1% to 13%) would have been classified as
success on the second but not the first. Of these 7 discrepancies (11%,
95% CI 5% to 21%), the most common was a difference between
“sometimes” and “rarely” (5/7, 71%). Discrepancies occurred across
the spectrum of strabismus types and ages.
Conclusions: Despite the importance of incorporating patient
report into outcome assessment, test-retest variability may lead
to misclassification, particularly when data are being used to
dichotomize into “success-failure.” Alternative strategies for cohort
studies include scoring on a continuous scale (as we previously
described for the Diplopia Questionnaire). Other approaches
might include using visual analog scales rather than descriptors, or
standardized definitions of those descriptors.
Commercial Relationships: Jonathan M. Holmes, None; David A.
Leske, None; Sarah R. Hatt, None
Support: NIH Grants EY024333 (JMH) and EY018810 (JMH),
Research to Prevent Blindness, and the Mayo Foundation.
Program Number: 1328
Presentation Time: 8:45 AM–9:00 AM
Quantitative Intraoperative Torsional Forced Duction Test
Jae Ho Jung1, 2, David A. Leske2, Jonathan M. Holmes2.
1
Ophthalmology, Pusan Nat’l Univ Yangsan Hospital, Yangsan, Korea
(the Republic of); 2Ophthalmology, Mayo Clinic, Rochester, MN.
Purpose: We developed a method for quantifying intraoperative
torsional forced ductions. We now describe performance of the
torsional forced duction test in patients with oblique dysfunction and
in controls, using photographic recording and reading of torsional
position.
Methods: We studied 25 patients with oblique dysfunction (9
with presumed congenital superior oblique palsy (SOP), 10 with
presumed acquired SOP, and 6 with Brown syndrome) and 31
controls (entirely normal forced duction tests prior to planned
horizontal muscle surgery). We also studied 3 of these patients while
the superior oblique (SO) was disinserted. After induction of deep
general anesthesia, the 6 and 12 o’clock positions at the limbus were
marked. A Mendez-ring was aligned with these reference marks and
a photograph was taken. The limbus was grasped with forceps, the
globe was maximally excyclorotated without retroplacement and then
maximal incyclorotated, and photographs were taken at each position.
Photographs were duplicated for evaluation of test-retest reliability,
and maximal excyclorotation and incyclorotation were read (in
degrees) by a masked observer. Intraclass correlation coefficients
(ICC) and 95% limits of agreement (LOA) were calculated. Maximal
excyclorotation and incyclorotation in each oblique dysfunction
condition were compared with controls.
Results: Test-retest reliability was excellent with a 95% LOA of 4.4
degrees and an ICC of 0.97. Eyes with presumed congenital SOP had
greater maximal excyclorotation than controls (mean±SD, 38.3±10.5
vs 29.3±5.5, p=0.01). Maximal excyclorotation in presumed acquired
SOP was similar to controls (27.3±4.7 vs 29.3±5.5, p=0.50). Eyes
with Brown syndrome had lower maximal excyclorotation than
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
controls (11.2±6.6 vs29.3±5.5, p=0.0007). Maximal excyclorotation
in cases with disinserted SO was greater than controls (52.0±3.5 vs
29.3±5.5, p=0.005). Maximal incyclorotation of presumed congenital
SOP, presumed acquired SOP, and Brown syndrome were similar to
controls (29.1±6.1, 28.7±4.7, 29.6±10.5 vs 32.5±6.6, all p>0.1).
Conclusions: Photographic reading of the new torsional forced
duction test shows excellent test-retest reliability. The torsional
forced duction test allows precise assessment of oblique muscle
tightness and laxity, and reflects differences between congenital SOP,
Brown syndrome, SO disinsertion and controls.
Commercial Relationships: Jae Ho Jung, None; David A. Leske,
None; Jonathan M. Holmes, None
Support: NIH Grants EY024333 (JMH) and EY018810 (JMH),
Research to Prevent Blindness, and the Mayo Foundation.
Program Number: 1329
Presentation Time: 9:00 AM–9:15 AM
Magnetic Resonance Imaging (MRI) Suggests New NonMuscular Constraints on Ocular Rotation in High Myopia
Joseph L. Demer. 1Ophthalmology, University of California, Los
Angeles, Los Angeles, CA; 2Neurology, University of California, Los
Angeles, Los Angeles, CA.
Purpose: Traditional concepts of motility assume a spherical globe
freely rotated by extraocular muscles (EOMs). This study employed
MRI to investigate the hypothesis that globe irregularity and the
optic nerve (ON) length may constrain ocular rotation in axial high
myopia..
Methods: High resolution, surface coil axial MRI using T1 or T2
fast spin echo sequences was obtained in 8 normal adults, 12 adult
esotropes (ET) with normal axial length (AL) <25.3 mm, 11 myopic
esotropes with mean AL 28.7±3.6 (SD) mm, and 7 exotropes (XT).
ON length was measured in eccentric horizontal gaze positions where
it became straight.
Results: ON straightening occurred only in adduction, at 23.6±9.0°
in normal subjects, not significantly different from XT at 22.2±11.8°,
but significantly greater in ET at 36.3±9.3°, and in myopic ET at
34.1±11.7° (P<0.003). ON length at straightening was 30.4±3.4 mm
in normals, not significantly different from XT at 30.7±2.6 mm, but
less in ET at 27.8±2.7 mm and 25.5±2.0 mm in myopic ET (P<0.03).
ET was associated with globe retraction and elongation in adduction,
suggesting ON tethering with forces concentrated at the scleral
canal. Eight globes of the myopes exhibited prominent irregular
nasal posterior, temporal posterior, nasal and temporal posterior,
or equatorial staphylomata. These scleral ectasias were positioned
to contact and elongate horizontal rectus EOM paths in some gaze
positions.
Conclusions: Concepts of strabismus in axial high myopes should
be expanded to include irregular posterior staphylomata, and
tethering in adduction by the ON. Staphylomata act like “cams”
affixed to the normally spherical globe, exerting no mechanical effect
until ecentrically rotating against EOMs. After rotational contact,
staphylomata would stretch and thus add tension to the EOM that
increases non-linearly with further duction. Tethering by the ON
can add a further strong nonlinear force opposing adduction, even
sufficient to deform the posterior pole.
Axial MRI in a highly myopic esotropic subject demonstrates
optic nerve straightening in adduction with globe retraction seen
as posterior shift of the corneal surface (green line). Posterior
staphylomata in this subject are evident from angulated posterior
contour of each globe. Ghost images anterior to the corneal surface
are motion artifacts due to retraction as the extraocular muscles pull
against the tethering optic nerve.
Commercial Relationships: Joseph L. Demer, None
Support: NIH Grant EY08313 and Research to Prevent Blindness
Program Number: 1330
Presentation Time: 9:15 AM–9:30 AM
Evidence for a Novel Genetic Link between Strabismus and
Schizophrenia
Austin J. Christensen1, Andrea B. Agarwal1, Cheng-yuan Feng1, Dan
Wen2, L. A. Johnson3, 1, Christopher S. von Bartheld1. 1Physiology
and Cell Biology, University of Nevada School of Medicine, Reno,
NV; 2Ophthalmology, Central South University, Xiangya Hospital,
Xiangya, China; 3Sierra Eye Associates, Reno, NV.
Purpose: Children with ocular misalignment (specifically exotropia)
have a greatly increased risk of developing schizophrenia decades
later, suggesting an overlapping genetic predisposition for both
diseases. The association of schizophrenia with exotropia but not
esotropia suggests that the two relevant rectus muscles (medial and
lateral) differ in their susceptibility to schizophrenia-related gene
products. We here determined (1) which genes that encode signaling
molecules are differentially expressed between strabismic and normal
human extraocular muscles, (2) how many of these genes overlap
with biomarkers or predisposing genes for schizophrenia, and (3)
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
which of these genes are differentially expressed between medial and
lateral rectus muscles.
Methods: Strabismic lateral and medial rectus muscle samples were
obtained during corrective surgeries according to IRB-approved
protocols; normal samples were obtained from deceased organ
donors. Consistent gene expression differences of 2-fold or more
on targeted or customized PCR arrays were compiled from paired
comparisons (n=4 per condition). We selected 84 genes of interest
based on known risk factors for schizophrenia.
Results: (1) Among 381 genes encoding signaling molecules, 22
were dysregulated in strabismic medial rectus muscle when compared
with normal medial rectus muscle. (2) Among those 22 genes,
almost half (10) were biomarkers for schizophrenia. (3) Among the
84 schizophrenia-related genes, 19 (=22.6%) were differentially
expressed in the medial rectus muscle, including cytokines, growth
factors and their receptors, and downstream signaling pathways
(AKT1, BDNF, BMP4, CNTF-R, ERBB2, MMP9, NGF, NOTCH1,
NTRK1, OSM, OLIG2, and multiple interleukins or their receptors).
Conclusions: Our data establish a molecular link between exotropia
and schizophrenia. This suggests that a combination of defects in
signaling molecules is relevant in the pathogenesis of both diseases.
Differences between medial and lateral rectus muscles in the
susceptibility to imbalanced signaling molecules may explain the
previously mysterious specific association between exotropia (but not
esotropia) and schizophrenia. The new findings may guide the design
of selective, muscle type-specific treatments of strabismus, as well
as enable the creation of a customized PCR array that can predict the
risk of schizophrenia 20 years prior to any symptoms, and possibly its
prevention.
Commercial Relationships: Austin J. Christensen, None; Andrea
B. Agarwal, None; Cheng-yuan Feng, None; Dan Wen, None; L. A.
Johnson, None; Christopher S. von Bartheld, None
Support: NIH Grants EY012841, GM103554
Program Number: 1331
Presentation Time: 9:30 AM–9:45 AM
Eye Movement Abnormalities in patients with Spinocerebellar
ataxia 3/Machado-Joseph disease
Fatema F. Ghasia1, George Wilmot2, Anwar Ahmed3, aasef shaikh3.
1
Ophthamology and visual science, Cole Eye Institute-Cleveland
Clinic, Lakewood, OH; 2Neurology, Emory University, Atlanta, GA;
3
Neurology, Cleveland Clinic, Cleveland, OH.
Purpose: Spinocerebellar Ataxia type 3(SCA3) or Machado-Joseph
disease is the most common inherited spinocerebellar ataxia. It
is the most common SCA associated with diplopia. We aimed to
characterize the type of strabismus and ocular motor abnormalities in
SCA3.
Methods: Eye movements and strabismus were clinically assessed
in 12 patients with SCA3. The saccadic eye movements and gaze
holding was objectively measured with a corneal curvature tracker
(Jazz Novo, Ober Consulting, Poland) and Eyelink SR 1000.
Results: Eight patients had ophthalmoplegia with mild abduction
deficit and three patients later developed an upward deficit. Ten
patients had strabismus.Three patients had esotropia, one patient had
skew deviation,one had a hypotropia accompanying the asymmetric
upward deficit, four patients had mild-moderate intermittent
exotropia, and one had moderate exophoria. The near point of
convergence was normal in the exotropic patients. Eight patients had
gaze-evoked nystagmus, eight had saccadic dysmetria, whereas all
twelve patients had saccadic pursuit. Two patients had slowing of the
saccades and five had microopsoclonus.
Conclusions: Strabismus and ophthalmoplegia were most common,
but saccadic oscillations were also notable in many patients.
The type of strabismus could not be explained by the co-existing
ophthalmoplegia or vergence abnormalities in our patients with
exotropia that comprised 50% of the cohort. It is possible that
involvement of the brainstem, the deep cerebellar nuclei and the
superior cerebellar peduncle are driving the exotropia in these
patients. Brainstem and deep cerebellar nuclei lesion also explains
microopsoclonus, while brainstem deficits can describe slow saccades
seen in our patients with MJD.
Commercial Relationships: Fatema F. Ghasia, None; George
Wilmot, None; Anwar Ahmed, None; aasef shaikh, None
Support: Knights Templar Eye Foundation, Fight for Sight Grant in
Aid
Program Number: 1332
Presentation Time: 9:45 AM–10:00 AM
Lingering fusional adaptation influences the Bielschowsky head
tilt test in superior oblique paresis
Kristina Irsch1, 2, David L. Guyton1, Howard S. Ying1. 1The Wilmer
Eye Institute, The Johns Hopkins University School of Medicine,
Baltimore, MD; 2Clinical Investigation Center – CIC 1423 INSERM,
Quinze-Vingts National Eye Hospital, Paris, France.
Purpose: To investigate how fusion influences the Bielschowsky
head tilt test in unilateral superior oblique paresis.
Methods: In eight fusing patients, we correlated haploscopicdetermined fusional mechanisms with Bielschowsky head tilt test
differences.
Results: Five patients used the vertical recti for vertical fusional
vergence and had a mean Bielschowsky head tilt test difference ±
SD of 22 ± 8 PD. After a 30-minute patch test one of those, in whom
the test was performed, showed a decrease of 10 PD. Two patients
used the “paretic” superior oblique muscle and the contralateral
superior rectus muscle to fuse, and had a mean Bielschowsky head
tilt test difference ± SD of 6 ± 8 PD. The Bielschowsky head tilt test
difference of one, in whom a patch test was performed, increased
by 11 PD. The remaining patient used the “paretic” superior oblique
muscle and contralateral inferior oblique muscle to fuse, and had a
Bielschowsky head tilt test difference of only 3 PD, increasing to 21
PD after patching.
One explanation for this behavior in the last patient involves lingering
vergence adaptation of the “paretic” superior oblique muscle and
contralateral inferior oblique muscle, which makes these muscles
more effective when activated on ipsilateral head tilt, lessening the
expected increase in hyperdeviation. Similarly, in our patients with
oblique/rectus-mediated fusion, the vergence-adapted “paretic”
superior oblique muscle and contralateral superior rectus muscle are
activated on ipsilateral and contralateral tilt respectively, lessening
the hyperdeviation in both directions. In the other five patients,
however, the vergence-adapted ipsilateral inferior rectus muscle and
contralateral superior rectus muscle are activated on contralateral tilt,
accentuating the Bielschowsky head tilt test difference.
Conclusions: Fusion influences the Bielschowsky head tilt test
difference, either decreasing or increasing this difference depending
on the particular muscle groups that are being used for fusion. The
absence of a positive Bielschowsky head tilt test should not be
relied upon to rule out the diagnosis of superior oblique paresis. In
suspected superior oblique paresis patients with fusion, performing
the Bielschowsky head tilt test after a patch test may be necessary to
bring out the Bielschowsky head tilt test difference supporting the
diagnosis.
Commercial Relationships: Kristina Irsch, None; David L.
Guyton, None; Howard S. Ying, None
Support: NIH R01 EY019347
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 1333
Presentation Time: 10:00 AM–10:15 AM
Complications of Botulinum Toxin-A for Treatment of Esotropia
in Children
Stephen P. Christiansen1, Danielle Chandler2, Katherine A. Lee3,
Rosanne Superstein4, Alejandra G. De Alba Campomanes5, Erick D.
Bothun6, David K. Wallace7, Raymond T. Kraker2. 1OphthalmologyBoston Med Ctr, Boston University School of Medicine, Boston,
MA; 2Jaeb Center for Health Research, Tampa, FL; 3St. Luke’s
Children’s Hospital, Boise, ID; 4Ophthalmology, Centre Hospitalier
Universitaire Sainte-Justine Hospital, University of Montreal,
Montreal, QC, Canada; 5Ophthalmology, University of California,
San Francisco, San Francisco, CA; 6Ophthalmology, University of
Minnesota, Minneapolis, MN; 7Duke Eye Center, Durham, NC.
Purpose: To report operative complications in children treated for
esotropia by botulinum toxin A (BTX-A) injection.
Methods: Subjects <17 years of age with esotropia were enrolled
in a 9-month data-collection study following BTX-A injection of
one or both medial rectus muscles. Subjects were managed as per
investigators’ routine clinical practice. Demographic, historical, and
pre-injection clinical data as well as details of the BTX-A injection
and perioperative complications were collected at enrollment.
Post-injection data from each visit through 9 months was collected
retrospectively.
Results: Twenty-seven subjects were enrolled at 13 sites. Esotropia
onset occurred before 6 months of age in 13 (48%) subjects and
after 6 months of age in 14 (52%). Eight (30%) subjects had prior
strabismus surgery, and 1 (4%) had prior BTX-A injection. Mean
age at injection was 3.9 ± 3.3 years (9 months to 13.8 years). BTX-A
injection was unilateral (n=7) or bilateral (n=20) and dosage ranged
from 3.0 to 6.0 units per muscle. Preoperative esodeviation, measured
by prism and alternate cover test, ranged from 10 to 65 PD (mean =
26 PD) at distance and from 12 to 65 PD (mean = 28) at near. Four
of 27 subjects (15%; 95% confidence interval [CI] = 4% to 34%)
experienced a complication from the injection. One subject (4%;
95% CI = 0% to 19%) had a left eye scleral perforation which was
noted at the time of injection and was treated by laser retinopexy
the same day with good visual and motor outcomes. Three subjects
(11%; 95% CI = 2% to 29%) developed tonic pupil noted at the first
post-injection visit. All three cases occurred in the left eye of subjects
who underwent BTX-A injection by the same surgeon, and were
characterized by delayed denervation hypersensitivity to pilocarpine
0.125%. The anisocoria diminished during the data collection period,
and there were no visual deficits.
Conclusions: Complications of BTX-A injection were encountered
in this small cohort of children with esotropia. Globe perforation is a
well-known complication of periocular injection. However, there are
few reports of tonic pupil after BTX-A injection. The mechanism of
action is unknown, but it may be direct trauma to the ciliary ganglion.
Other possible explanations include anticholinergic toxicity from
intraconal diffusion of BTX-A affecting the ciliary ganglion and/or
intraocular diffusion affecting the pupillary sphincter.
Commercial Relationships: Stephen P. Christiansen, None;
Danielle Chandler, None; Katherine A. Lee, None; Rosanne
Superstein, None; Alejandra G. De Alba Campomanes, None;
Erick D. Bothun, None; David K. Wallace, None; Raymond T.
Kraker, None
Support: NIH Grants EY018810, EY023198, and EY011751
236 New insights into strabismus mechanisms: Central and
peripheral influences - Minisymposium
Monday, May 04, 2015 11:00 AM–12:45 PM
4CD Mile High Blrm Minisymposium
Program #/Board # Range: 1705–1709
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Program Number: 1705
Presentation Time: 11:00 AM–11:05 AM
New Insights into Strabismus Mechanisms: Central and
Peripheral Influences
Howard S. Ying. Johns Hopkins University, Baltimore, MD.
Presentation Description: Strabismus is most commonly a
developmental disorder wherein disruption of binocular vision in
the critical period of visual and oculomotor development leads to
permanently misaligned eyes. This symposium will provide an
overview of recent basic science work that has examined the role of
various central (brain) and peripheral (extraocular muscle) factors in
the development and maintenance of the strabismic state.
Commercial Relationships: Howard S. Ying, Lutronics, Inc. (C),
The Johns Hopkins University (P)
Support: NIH grant EY19347
Program Number: 1706
Presentation Time: 11:05 AM–11:30 AM
The Control of Ocular Alignment During Infancy and Early
Childhood
T. R. Candy. Indiana University, Bloomington, IN.
Presentation Description: Infants are typically hyperopic while
having a reduced interpupillary distance relative to adults. Despite the
neural coupling between the two systems, infants must overcome the
relatively increased accommodative demand and reduced vergence
demand in order to remain aligned and avoid refractive strabismus.
Interestingly, the mean age of onset of refractive esotropia is not until
two to three years of age, and only a subset of hyperopes develop
the deviation. This presentation will explore the control of ocular
alignment during infancy and early childhood, specifically examining
the role of accommodative performance, heterophoria, vergence
ranges and vergence adaptation during this period. The implications
for the management of young hyperopes will also be addressed.
Commercial Relationships: T. R. Candy, None
Support: NIH: R01 EY014460, P30 EY019008
Program Number: 1707
Presentation Time: 11:30 AM–11:55 AM
MRI studies of extraocular muscle in humans with strabismus
Joseph L. Demer. Stein Eye Institute and Departments of
Ophthalmology & Neurology, University of California, Los Angeles,
Los Angeles, CA.
Presentation Description: Externally observable oculomotor
behavior consists of only 3 degrees of rotational freedom for each
of 2 eyes. Unsurprisingly, contractile states and pulling directions
of 12 oculorotary muscles (EOMs), each consisting of at least 2
functional compartments, cannot be uniquely determined from eye
movement observations. This “overdetermination” is problematic
in understanding mechanistic causes of strabismus, which may
variously arise from central or peripheral disorders of neural control,
or disorders of EOM strength, elasticity, and pulling direction.
High resolution magnetic resonance imaging (MRI) provides a useful
approach to this conundrum. MRI can demonstrate orbital connective
tissue anatomy, and the anatomy and contractile states of EOMs.
Surface coils and target-controlled fixation enable near microscopic
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
structural resolution. Repeated MRI in varying gaze positions
enables demonstration of EOM contractility evidenced by changes
in cross section distribution and volume, and changes in EOM paths
indicating pulling directions.
MRI demonstrates several mechanical causes of strabismus. For
example, congenital A and V patterns are due to heterotopy of rectus
pulleys. The sagging eye syndrome is a common degenerative cause
of acquired distance esotropia and cyclovertical strabismus resulting
principally from failure of a ligament interconnecting the lateral and
superior rectus pulleys, along with EOM elongation. Globe position
and shape abnormalities interact with connective tissue and EOM
pathology in strabismus associated with axial high myopia.
MRI also clarifies strabismus caused by neural or muscular
disorders that alter EOM stiffness, or impair force generation.
MRI also demonstrates deficient contractility and hypoplasia in
congenital dysinnervation disorders, and in acquired innervation
abnormalities, including trochlear, abducens, and oculomotor palsy.
MRI demonstrates regional lateral rectus atrophy presumably due
to selective denervation of one of the two abducens motor nerve
branches.
Since motor neurons in the ocular motor system innervate EOMs
to indirectly influence rather than directly control EOM force and
eye orientation, EOM functional anatomy should have a closer
relationship with motor neuron behavior than does eye position.
Commercial Relationships: Joseph L. Demer, None
Support: USPHS National Eye Institute EY08313
Program Number: 1708
Presentation Time: 11:55 AM–12:20 PM
Cellular changes in extraocular muscle in strabismus and
nystagmus
Linda K. McLoon. University of Minnesota, Minneapolis, MN.
Presentation Description: The extraocular muscles are normally
precisely controlled by the ocular motor system to ensure that
the same areas of the visual world land on the fovea of each eye.
Strabismus and infantile nystagmus syndrome represent a failure
of that precise control. Extraocular muscles removed as surgical
waste from these patients were examined to demonstrate patterns of
innervational changes. In the extraocular muscles of subjects with
nystagmus, innervation was sparse and the neuromuscular junctions
smaller than normal with many more junctions expressing the
immature subunit of the acetylcholine receptor. In the extraocular
muscles of subjects with “motor” strabismus, there was a higher
density of innervation. In addition, in the strabismic extraocular
muscles, increased connective tissue density was seen. We are
currently looking to see if these changes are adaptations to abnormal
signaling derived from their innervating motor neurons, and whether
these abnormal findings can be corrected by treatments at the level of
the extraocular muscles.
Commercial Relationships: Linda K. McLoon, None
Support: Supported by NIH grants RO1EY15313 (LKM) and
EY11375 from the National Eye Institute, University Medical
Foundation, Minnesota Lions and Lionesses, and an unrestricted
grant to the Department of Ophthalmology and Visual Neurosciences
from Research to Prevent Blindness, Inc.
Program Number: 1709
Presentation Time: 12:20 PM–12:45 PM
Investigation of oculomotor structures in monkey models for
strabismus
Vallabh E. Das. College of Optometry, University of Houston,
Houston, TX.
Presentation Description: Disruption of binocular vision during
the early critical period for development leads to disruption in
development and calibration of visual and oculomotor areas and
eventually misaligned eyes. Our approach to investigate the neural
component of this disorder has been to first develop appropriate
non-human primate models and thereafter to perform behavioral
and neurophysiological investigation of oculomotor circuits in these
animals. In this symposium presentation, we will present results
from these studies that together suggest that a circuit that serves
slow vergence eye movements in the normal animal is involved in
setting the state of eye misalignment in a sensory form of strabismus.
We will also present preliminary data showing the nature of neural
plasticity following strabismus correction surgery in animals with
strabismus.
Commercial Relationships: Vallabh E. Das, None
Support: NIH Grant R01 EY015312; NIH Grant R01 EY022723;
NIH Grant P30 EY07551
276 Amblyopia / Refractive errors
Monday, May 04, 2015 3:45 PM–5:30 PM
Exhibit Hall Poster Session
Program #/Board # Range: 2183–2215/B0036–B0068
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Contributing Section(s): Clinical/Epidemiologic Research, Visual
Psychophysics/Physiological Optics
Program Number: 2183 Poster Board Number: B0036
Presentation Time: 3:45 PM–5:30 PM
Characteristics of Anterior Polar Cataracts in Children
Lena Dixit1, Michael Puente1, Kimberly Yen2. 1Ophthalmology,
Baylor College of Medicine, Houston, TX; 2Ophthalmology, Texas
Children’s Hospital, Houston, TX.
Purpose: To evaluate pediatric patients with unilateral or bilateral
anterior polar cataracts and assess the development of astigmatism,
rate of amblyopia, change in visual acuity, and need for surgery over
time.
Methods: A retrospective chart review was performed on patients
examined at Texas Children’s Hospital in Houston, Texas from 2008
to 2014. Patients with unilateral or bilateral anterior polar cataracts
(APCs) were included in the study. Patients with mixed etiology
cataracts or other causes of poor visual acuity were excluded.
Size, location, and type of anterior polar cataract were assessed.
Best corrected visual acuity and refraction were recorded from the
initial visit and subsequent encounters. Development of amblyopia,
anisometropia, and astigmatism were recorded. Size and type of
cataract were correlated with the development of each outcome.
Statistical analysis was performed on each categorical variable with
significance set at p < 0.05.
Results: A total of 31 patients were included in the study. 17 patients
had unilateral APCs and 14 had bilateral APCs. 83% were centrally
located and 17% were non-central. 40% of patients had concurrent
ocular conditions and 10% had systemic associations. 21% of patients
with bilateral cataracts developed amblyopia compared to 35% in
the unilateral population. 29% of patients with bilateral cataracts
had anisometropia compared to 24% in the unilateral population. 3
patients required surgical intervention.
Conclusions: Most anterior polar cataracts are less than 1 mm in size
and of the polar type. Risk of amblyopia is higher than the general
population. Anisometropia is the most common cause of amblyopia.
Ocular and systemic associations can occur but are uncommon.
Surgical treatment is uncommon; however, growth of APCs,
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
pyramidal type, and associated cortical changes may be risk factors
for surgery.
Commercial Relationships: Lena Dixit, None; Michael Puente,
None; Kimberly Yen, None
Program Number: 2184 Poster Board Number: B0037
Presentation Time: 3:45 PM–5:30 PM
The effects of Monocular Training on Binocular Functions in
Adult Amblyopia
Chang-Bing Huang1, Wuli Jia1, WUXIAO ZHAO3, Zhong-Lin Lu2.
1
Institute of Psychology, CAS, Beijing, China; 2Department of
Psychology, The Ohio State University, Columbus, OH; 3Center for
Optometry and Visual Science,, The People’s Hospital of Guangxi
Zhuang Autonomous Region, Nanning, China.
Purpose: It’s now clear that intensive monocular perceptual learning
can improve visual acuity, contrast sensitivity, and vernier acuity
in the amblyopic eye of adults with amblyopia. It is however not
clear how much monocular training can enhance binocular vision.
In the current study, we aimed to determine the effects of monocular
training on a variety of binocular visual functions.
Methods: Eleven adults with anisometropic amblyopia (22±1.4 yrs)
were trained in a grating contrast detection task near each individual’s
cutoff spatial frequency for 8 to 10 days, with 630 trials/day. Visual
acuity, stereo acuity, monocular and binocular contrast sensitivity
functions (CSF) with the quick CSF method (Lesmes, et al., 2010),
perceived phase of binocularly combined sinewave gratings as a
function of interocular image contrast ratio (Huang et al., 2009), pAE
dominance in viewing dichoptically presented incompatible images
of equal contrasts were measured before and after training.
Results: Training substantially improved contrast sensitivity at
the trained spatial frequency (by 75.4%), area under the CSF (by
94%), and visual acuity (logMAR from 0.62 to 0.42 or 2 lines)
in the amblyopic eye. It also significantly improved stereo acuity
(from 1530.9” to 110.7”) and increased the dominance duration
of the amblyopic eye (from 2% to 13% in binocular rivalry). The
improved dominance of the amblyopic eye was through elongation
of each dominant phase without alteration of the switching frequency
between the two eyes. On the other hand, training didn’t significantly
improve the ratio of the areas under binocular and monocular fellow
eye CSFs (from 1.1 to 1.08, p>0.1) and the interocular contrast
ratio at which the two eyes contribute equally to binocular phase
combination (from 0.11 to 0.13, p>0.10). There is no significant
correlation between improvements in visual acuity, stereo acuity, and
binocular rivalry.
Conclusions: Although monocular training can improve visual acuity
and contrast sensitivity and eye dominance of the amblyopic eye, the
magnitudes of improvements didn’t correlate with each other; the
impact on binocular summation and binocular phase combination was
not significant. The results strongly suggest that structured monocular
and binocular training is necessary to fully recover deficient visual
functions in amblyopia.
Commercial Relationships: Chang-Bing Huang, None; Wuli Jia,
None; WUXIAO ZHAO, None; Zhong-Lin Lu, Adaptive Sensory
Technology, LLC. (I), The Ohio State University (P)
Support: Supported by National Natural Science Foundation of
China (NSFC 31230032 and 31470983), the Knowledge Innovation
Program of the Chinese Academy of Sciences (Y3CX102003),
Institute of Psychology, CAS to Chang-Bing Huang, and NEI
(EY021553) to Zhong-Lin Lu.
Program Number: 2185 Poster Board Number: B0038
Presentation Time: 3:45 PM–5:30 PM
A Randomized Trial of AmblyzTM Intermittent Occlusion Glasses
vs Traditional Patching for Treating Children with Moderate
Unilateral Amblyopia
Jingyun Wang, Daniel Neely, Jay Galli, Joshua Schliesser, Tina
Damarjian, Heather Smith, Dana Donaldson, Kathryn M. Haider,
Derek Sprunger, David Plager. Glick Eye Institute, Department of
Ophthalmology, Indiana University School of Medicine, Indianapolis,
IN.
Purpose: PEDIG studies suggest a 2-hour patching treatment is
effective for children with moderate amblyopia. Amblyz™ liquid
crystal occlusion glasses are able to occlude the eye intermittently for
periods of 30 seconds. Therefore, we hypothesized that 4-hour daily
intermittent occlusion from Amblyz™ glasses is equally effective
to 2-hour daily patching occlusion. Although a previous nonrandomized pilot study suggested that liquid crystal occlusion glasses
are effective treating amblyopia (Spierer et al. 2010), there has not
been prior comparison to a patching control group. This randomized
clinical trial is designed to compare the effectiveness of Amblyz™
glasses versus adhesive patching for treating moderate, unilateral
amblyopia in children.
Methods: Children (N=28, age=5.3±1.4YR, 3- to 8-year-old) with
previously untreated, moderate, unilateral amblyopia (visual acuity
of 20/40 to 20/100 in the amblyopic eye) were enrolled. All subjects
had worn optimal refractive correction (if needed) for at least 12
weeks without improvement and their amblyopia was associated
with strabismus, anisometropia, or both. Subjects were randomized
into one of two treatment groups: a 4-hour daily Amblyz™ Glasses
Group with liquid crystal shutter set at 30-second opaque/transparent
intervals, or the 2-hour adhesive Patching Control Group. For each
patient, visual acuity was measured with ATS-HOTV methods before
and after 12 weeks of treatment.
Results: At the conclusion of the first 12 week-treatment
interval, visual acuity in the amblyopic eye improved an average
of 0.22±0.11logMAR in the Amblyz™ Glasses Group and
0.21±0.16logMAR in the Patching Group. Vision improvements
in both groups were clinically significant (p<0.05, over 2 lines).
There was no statistically significant difference between groups
(P-value=0.75). We did not find reverse amblyopia in the fellow
eye. Compliance and treatment experience are reported in a related
abstract.
Conclusions: Our pilot data showed that intermittent occlusion
associated with AmblyzTM glasses is equally effective to patching
occlusion when treating 3-8 year old children with moderate
amblyopia. This new device is a promising alternative treatment for
amblyopia. The apparent effectiveness of Amblyz™ glasses warrants
further investigation with longer follow-up and larger sample size.
Commercial Relationships: Jingyun Wang, None; Daniel Neely,
None; Jay Galli, None; Joshua Schliesser, None; Tina Damarjian,
None; Heather Smith, None; Dana Donaldson, None; Kathryn M.
Haider, None; Derek Sprunger, None; David Plager, None
Support: Research to Prevent Blindness (RPB) Unrestricted Grant to
the Glick Eye Institute
Clinical Trial: NCT01973348
Program Number: 2186 Poster Board Number: B0039
Presentation Time: 3:45 PM–5:30 PM
Compliance with AmblyzTM Liquid Crystal Glasses Versus
Traditional Adhesive Patches
Paxton Ott, Daniel Neely, Jingyun Wang, Jay Galli, Heather Smith,
Dana Donaldson, Kathryn M. Haider, Derek Sprunger, David Plager.
Ophthalmology, Indiana University School of Medicine, Clayton, IN.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Purpose: Amblyopia treatment with adhesive occlusion patches is
frequently inhibited by poor compliance and complaints. Amblyz™
liquid crystal glasses utilize an intermittent occlusion technique
(at 30-second opaque/transparent intervals) and avoid adhesives,
potentially improving compliance. Despite the easier administration
of Amblyz glasses, they require double the amount of wearing time
compared to patching which may undercut compliance. This study
compares compliance with AmblyzTM glasses versus patching.
Methods: Children (N=28, age=5.3±1.4YR, 3- to 8-year-old) with
previously untreated, moderate, unilateral amblyopia (visual acuity
of 20/40 to 20/100 in the amblyopic eye) were enrolled. All subjects
wore optimal refractive correction (if needed) for at least 12 weeks
and their amblyopia was associated with strabismus, anisometropia,
or both. Subjects were randomized into one of two treatment
groups: a 4-hour Amblyz™ Glasses Group, or a 2-hour Patching
Control Group. After 12 weeks, compliance was reported with a
calendar log and an Amblyopia Treatment Index (ATI) questionnaire
characterizing the experience. Weekly compliance was calculated
using the total weekly-treated minutes divided by the total weeklyprescribed minutes.
Results: At the conclusion of the first 12 week-treatment interval,
compliance averaged 85% in the Patching Group and 79% in
the AmblyzTM Group (P=0.23, no statistical difference). Weekly
compliance varied among individuals. No adverse effects were
reported. Similar to the Patching Group, children in the AmblyzTM
Group struggled with some outdoor activities, but reported no
issues with indoor activities. In the AmblyzTM Group, some parents
reported that their child had trouble seeing outside at night secondary
to the tint inherent to the liquid crystal lenses; also, some parents
complained that the glasses were easily subject to damage by
their child. The ATI questionnaire demonstrated a high level of
enthusiasm from parents and children with the Amblyz™ glasses,
commonly remarking that they were easier to wear and generated
fewer complaints. Visual outcome measures are reported in a related
abstract.
Conclusions: Compliance with AmblyzTM glasses is similar to
patching, even when wearing time was doubled in this trial. This
device promotes a relatively comfortable experience for the child
and is a promising alternative to the traditional patching amblyopia
treatment.
Commercial Relationships: Paxton Ott, None; Daniel Neely,
None; Jingyun Wang, None; Jay Galli, None; Heather Smith,
None; Dana Donaldson, None; Kathryn M. Haider, None; Derek
Sprunger, None; David Plager, None
Clinical Trial: NCT01973348
Program Number: 2187 Poster Board Number: B0040
Presentation Time: 3:45 PM–5:30 PM
Feasibility Study in Normal Children of a Liquid Crystal
Spectacle Filter (LCSF) for Potential Treatment of Amblyopia
Megan Cochran1, 2, Richard W. Hertle1, Paul Luchette3, Kajal
Jassemnejad3, Sandip Bhatta3, Tamas Kosa3, Bahman Taheri3,
Volodymyr Bodnar3. 1Akron Children’s Hospital, Akron, OH; 2Ohio
University Heritage College of Osteopathic Medicine, Athens, OH;
3
Alpha Micron, Kent, OH.
Purpose: To evaluate a new LCSF device applied to commercial
eyeware for both comfort and the potential to reduce visual acuity
Methods: AlphaMicron Inc. Kent, Ohio, has developed a liquid
crystal system designed specifically for eyewear which uses a
polymer liquid crystal mixture consisting of “guest” monomers in a
liquid crystal “host”. This mixture is sandwiched between two curved
flexible plastic substrates coated with transparent electrodes. By
applying voltage to the substrates, the electro-optic response of the
liquid crystal mixture is used to control the opacity of the device. The
voltage is applied manually with a touch of a button or automatically
through a sensor, providing instantaneous control over transmission.
20 normal children ages 7-10 were testing while wearing the LCSF.
The amount of light transmission measure as a voltage was correlated
to monocular and binocular visual acuity degradation using the
PEDIG acuity testing paradigm.
Results: The LCSF is successfully able to depress visual acuity in a
linear fashion by changing the “haze” or light transmission function
in a stepwise fashion from 20/20 to light perception.
Conclusions: The LCSF filter may provide multiple benefits in the
treatment of, including; ease of application to commercially available
eyeware, cosmetic appeal, comfort, versatility in occlusion dosage
and the potential to improve adherence.
This is the LCSF prototype showing full light transmission above and
no light transmission below.
This curve shows the relationship between light transmission and
visual acuity.
Commercial Relationships: Megan Cochran, None; Richard
W. Hertle, None; Paul Luchette, Alpha Micron (E); Kajal
Jassemnejad, Alpha Micron (E); Sandip Bhatta, Alpha Micron (E);
Tamas Kosa, Alpha Micron (E); Bahman Taheri, Alpha Micron (E);
Volodymyr Bodnar, Alpha Micron (E)
Program Number: 2188 Poster Board Number: B0041
Presentation Time: 3:45 PM–5:30 PM
Objective compliance, dose, and response for atropine
penalization amblyopia treatment
Scott O’Brien, Lyne Racette, Heather Smith, Kathryn M. Haider,
Dana Donaldson, Derek Sprunger, Daniel Neely, David Plager,
Jingyun Wang. Glick Eye Institute Department of Ophthalmology,
Indiana University School of Medicine, Indianapolis, IN.
Purpose: According to previous studies, a daily regimen (7 drops
a week) of atropine penalization is equally effective to a 2-drop
regimen (2 drops a week) in treating moderate and severe amblyopia.
These results suggest that the dose-response relationship of atropine
penalization is not fully understood. Parental self-reported subjective
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
compliance to atropine penalization ranges from 59% to 94%.
(PEDIG, 2002, 2008, 2009) Objective measurement of compliance
to atropine penalization has not been reported. This study aims to
investigate objective compliance, dose, and vision improvement
response to atropine penalization in amblyopic children.
Methods: Twelve amblyopic children (3-8yr; 20/40-20/125 in the
amblyopic eye, not previously treated with atropine) were enrolled.
Twice weekly or daily regimen was prescribed by physicians.
To measure objective compliance, we used Medication Event
Monitoring System (MEMS) caps, which are designed to record the
time and date when the bottle was opened. Objective compliance
was calculated as the ratio of MEMS weekly recording times to
weekly regimen. Participants were provided a calendar log to report
subjective compliance and were scheduled for follow-up visits at
4 and 12 weeks. To measure the usage of atropine, we weighed the
atropine eyedropper before and after treatment. Visual acuity was
measured with ATS-HOTV. Correlation of visual acuity improvement
with total atropine usage and regimen were calculated.
Results: At 4 weeks, objective compliance averaged 78% (range
57-100%), while subjective compliance was reported to be 84%
(range 64-100%). At 12 weeks, the average objective compliance
was 62% (range 41-100%), while subjective compliance was 84%
(range 78-100%). Interestingly, we found that the twice a week
regimen had significantly higher objective compliance than the daily
regimen (p=0.03). Visual acuity in the amblyopic eye improved
0.23±0.18logMAR. Data suggests that visual acuity improvement
is correlated to total atropine usage (R-squared =0.73), instead of
regimen (R-squared =0.10).
Conclusions: Objective compliance with atropine instructions can
be monitored with MEMS, which may facilitate more effective
communication between clinicians and patients. Our pilot data
showed that objective compliance with atropine penalization
treatment decreases over time and varies with regimen. On average,
subjective parental reporting of compliance is overestimated.
Commercial Relationships: Scott O’Brien, None; Lyne Racette,
None; Heather Smith, None; Kathryn M. Haider, None; Dana
Donaldson, None; Derek Sprunger, None; Daniel Neely, None;
David Plager, None; Jingyun Wang, None
Support: Indiana CTSI PDT
Program Number: 2189 Poster Board Number: B0042
Presentation Time: 3:45 PM–5:30 PM
Problems in occlusion therapy – a qualitative study with parents
and educators
Charlotte Schramm1, Sybille Gräf1, Natalia Radionova1, Monika
A. Rieger2, Dorothea Besch1, Kai Januschowski1. 1Ophthalmology,
University hospital, Tuebingen, Germany; 2Institute for Occupational,
Social Medicine and Health Services Research, Tuebingen, Germany.
Purpose: The main problem while treating amblyopia (weaksightedness) is malcompliance of both - children and parents
- to occlusion instructions/ guidelines. The aim of this study is a
description of the current situation and problems of occlusion therapy
in Germany using structured interviews.
Methods: We performed 25 single structured interviews with adults
who are involved in occlusion therapy as parents, educators or
former patients who were treated with occlusion therapy in their
childhood. Interviews were performed with persons of each of the
following groups: parents and day-care workers of children with
well-functioning therapy as well as parents and day-care workers
of children with mal-functioning therapy and adults who received
an occlusion therapy themselves in their childhood. The interview
partners were recruited over the outpatient clinic in the University
Eye Clinic Tuebingen, Department for strabology, motility disorders
and children diseases. For the interviews standardized questions were
used and different sociodemographic data according to the interview
partner assessed additionally. Qualitative data analysis was carried
out using Mayring’s content analysis method.
Results: The analysis shows that occlusion therapy works fine in
public day-care centers in spite of the anxiety of the most parents.
In the age of 2 to 6 years social discrimination or isolation is not
common. But an important point and potential pitfall in therapy
compliance is the missing information about amblyopia of day-care
workers. Day-care workers in Germany are officially not authorized
care about the childrens’ health issues like administering drugs.
However, the interviewed day-care workers felt responsible and
coped well with patching therapy. The social background of the
patients seems not to have an impact on dealing with occlusion
therapy.
Conclusions: Against current view performing occlusion therapy in
day-care centers is a good alternative to patching at home. This is
important considering that mothers tend to return to their working
life soon following childbirth. Therefore day-care is more and
more carried out in different forms (like kindergarten or nanny)
and an official authorization for day-care workers to care about the
childrens` health issues has to be politically discussed. Moreover, a
better information of day-care workers about occlusion therapy is
necessary.
Commercial Relationships: Charlotte Schramm, None; Sybille
Gräf, None; Natalia Radionova, None; Monika A. Rieger, None;
Dorothea Besch, None; Kai Januschowski, None
Support: This study was supported by an external peer reviewed
funding of the “Nachwuchsakademie Versorgungsforschung BadenWuerttemberg”
Program Number: 2190 Poster Board Number: B0043
Presentation Time: 3:45 PM–5:30 PM
Visual outcomes of treatment of anisometropic and strabismic
amblyopia in Mexican children older than 7 years
Raul Alfaro, Guillermo Mendoza, Juan Homar Paez, Hector Morales.
Tecnologico de Monterrey, Monterrey, Mexico.
Purpose: To evaluate visual outcomes of patients treated for
anisometropic or strabismic amblyopia in children aged 7 to 17
years, treated in our clinic from 2008 to 2014, and compare the visual
acuities from these groups.
Methods: Retrospective, longitudinal, and observational study.
Were included patients in our clinic with diagnosis of anisometropic
or strabismic amblyopia without any other eye disease, which have
at least 6 months follow up visit. All patients with anisometropic
amblyopia were provided with optical correction and depending on
visual acuity were treated with patching 2, 4 or 6 hours. The patients
with strabismic amblyopia were treated with patching depending their
visual acuities and with optical correction if was needed, and surgery.
Analysis of variance and analytical observation were used to compare
visual outcomes presented through time.
Results: The visual acuity at the diagnosis was .88logMar (20/150)
in anisometropic patients and for the strabismic was .56logMar.
(20/70). The visual acuity mean after 6 months of treatment was
.34logMar. (20/42) for anisometropic patients and for strabismic
patients was .28logMar (20/38). After analysis of variance it was
found a statistically significant difference in visual acuity (P <.05)
in both groups at 3 months and 6 months of treatment, nevertheless
comparatively both groups gained visual acuity without any
statistically significant variation,which means there was not founded
any significant distinction in visual acuity improvement related to an
ocular condition, but there is improvement during treatment.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Conclusions: According to the results of this analysis treatment
of amblyopia in patients older than 7 years is effective, and the
outcomes in visual acuities are similar in both strabismic and
anisometropic patients. To date, there are few studies on this subject
and to our knowledge the are no studies comparing the result of
treating strabismic vs anisometric amblyopia in this group age.
Commercial Relationships: Raul Alfaro, None; Guillermo
Mendoza, None; Juan Homar Paez, None; Hector Morales, None
Program Number: 2191 Poster Board Number: B0044
Presentation Time: 3:45 PM–5:30 PM
Dichoptic virtual reality therapy for amblyopia in adults
Christopher M. Aderman1, Michael Deiner1, Manish Gupta2, James
Blaha2, Marc H. Levin1. 1Ophthalmology, University of California,
San Francisco, San Francisco, CA; 2Apollo VR, San Francisco, CA.
Purpose: Studies suggest binocular video game therapies may
effectively treat amblyopia in older children and adults, who are
outside the critical window for traditional patching. Dichoptic video
game training involves complementary game elements shown to both
eyes, with the amblyopic eye seeing a higher contrast image. We are
evaluating the safety and efficacy of a new immersive virtual reality
(VR) system as a dichoptic amblyopia therapy. An additional study
aim is to validate at home VR-based therapy and to compare visual
parameters with in-office clinical examinations.
Methods: We are conducting a single-center, masked, placebocontrolled study of the effect of 3-dimensional, VR gameplay
on visual acuity (VA) and stereopsis in subjects with amblyopia.
Approximately 50 participants between the ages of 15 and 45 with
moderate vision loss from anisometropic and/or strabismic amblyopia
are being enrolled. Subjects are randomized into three arms,
comparing at-home dichoptic gameplay to monocular patching or
binocular non-dichoptic gameplay. After an initial three-week period
of patching or gameplay at home, all subjects receive the dichoptic
intervention for an additional three weeks. Office-based testing is
supplemented with novel in-game at-home diagnostic testing and
compliance monitoring. Durability of treatment will be evaluated
six months after enrollment. Primary study outcomes are VA in the
amblyopic eye and stereopsis. Secondary outcomes include quality of
life (AS-20 questionnaire), binocular Sloan low contrast acuity, and
safety.
Results: Pilot data supports a beneficial effect in amblyopic patients,
with reduced suppression after 3 hours of gameplay. More than 300
users have trialed this system without reporting persistent diplopia
or other bothersome side effects. In control subjects with varied
levels of vision, measures of acuity and stereopsis from clinical
examinations correlate with in-game testing metrics.
Conclusions: Dichoptic VR treatment may be safe and effective
in reducing suppression in young adults with amblyopia. Our
randomized-controlled study will formally test the effects of
dichoptic VR therapy on VA and stereopsis. Home-based VR systems
also enable remote diagnostics and monitoring and should encourage
compliance. Our initial results also support a role for remote testing
in rigorous studies of candidate vision therapies.
Commercial Relationships: Christopher M. Aderman, None;
Michael Deiner, None; Manish Gupta, Apollo VR (I); James
Blaha, Apollo VR (I); Marc H. Levin, None
Clinical Trial: NCT02246556
Program Number: 2192 Poster Board Number: B0045
Presentation Time: 3:45 PM–5:30 PM
Effect of monocular perceptual learning on binocular
combination in anisometropic amblyopia
Zidong Chen, Jinrong Li, Junpeng Yuan, Daming Deng, Minbin Yu.
Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou,
China.
Purpose: Perceptual learning of contrast detection can improve
monocular visual function in adult amblyopes (Huang, 2008, PNAS).
The effect of such training paradigm on binocular combination
condition remains unknown. This study aimed to assess the binocular
combination outcome after monocular perceptual learning in
anisometropic amblyopes beyond critical period.
Methods: Ten young participants with anisometropic amblyopia
(age: 8-20) performed 2AFC grating contrast detection task near
cut-off spatial frequency in the amblyopic eye for 7-12 days. Contrast
sensitivity function (CSF), binocular function measurement using (1)
binocular phase combination, (2) global dichoptic motion coherence,
visual acuity (VA), and randot stereo acuity were assessed before and
after training. Another ten subjects with anisometropic amblyopia
(age: 7-16) prescribed patching for 4h/d and followed up in 2 weeks
served as control.
Results: Monocular perceptual learning significantly improved
visual acuity in the amblyopic eye (1.68±0.08 lines, P=0.0002) and
contrast sensitivity (CS) at trained spatial frequency (8.83±3.04
dB, P=0.0001). Change of binocular combination was observed
by measuring effective contrast ratio (ECR) in (1) binocular phase
combination task at spatial frequency of 0.3 cycle per degree
(P=0.015; N=10), and (2) dichoptic motion coherence task (P=0.013;
N=8). Area under log CSF (AULCSF) was calculated. Improvement
of AULCSF in the amblyopic eye was found to be correlated with the
improvement of ECR in binocular phase combination task (R=0.733,
P=0.016) and VA (R=0.71,P=0.021). Change of binocularly perceived
phase after training was observed only when low contrast stimuli
was presented to the non-amblyopic eye, but not when higher
contrast stimuli was used. Patching group didn’t show significant
improvement in either visual acuity or binocular combination in 2
weeks.
Conclusions: Monocular perceptual learning in anisometropic
amblyopia could improve visual acuity in amblyopic eyes and change
binocular combination condition. Improvement of CSF may be the
underlying mechanism. However, such training paradigm was not
sufficient to establish normal binocular vision in amblyopes when
images of identical contrast were presented to both eyes.
Commercial Relationships: Zidong Chen, None; Jinrong Li,
None; Junpeng Yuan, None; Daming Deng, None; Minbin Yu,
None
Support: National Natural Science Foundation of China Grant
(81200715) and Fundamental Research Funds of State Key
Laboratory of Ophthalmology to Jinrong Li
Program Number: 2193 Poster Board Number: B0046
Presentation Time: 3:45 PM–5:30 PM
Improving visual functions in adult amblyopia with combined
perceptual training and transcranial random noise stimulation
(tRNS): a pilot study
Antonella Veronese1, Giuseppe Lo Giudice1, Gianluca Campana2,
Rebecca Camilleri2, Andrea Pavan3, Alessandro Galan1.
1
Ophthalmology, San Antonio Hospital, Padova, Italy; 2General
Psychology, University of Padova, Padova, Italy; 3Institut fur
Experimentelle Psychologie, University of Regensburg, Regensburg,
Germany.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Purpose: to assess whether a much shorter perceptual training
regime, in association with high-frequency transcranial electrical
stimulation (hf-tRNS), was able to improve visual functions in a
group of adult participants with amblyopia.
Methods: Seven participants with anisometric amblyopia were
recruited at the San Paolo Ophthalmic Center of San Antonio
Hospital (Padova, Italy).
The participants were enrolled in a 2-week (8 sessions) behavioural
training programme using a contrast detection task under lateral
masking conditions combined with online high frequency tRNS (hftRNS). All pre/post tests were administered monocularly on either
eye and with the best optical correction. Perceptual training was also
administered monocularly on the amblyopic eye with the best optical
correction.
Exclusion criteria included any other ocular condition or cause
for reduced VA other than amblyopia, myopia, presbyopia,
hypermetropia and/or astigmatism; these include diabetes mellitus,
pregnancy, presence of myopia-related ocular complications and
any previous ocular surgery. Exclusion criteria also included
incompatibility with transcranial electrical stimulation, as assessed
with a questionnaire (e.g. history of seizures, skin problems,
migraine, etc.). This study has been approved by the local Ethics
Committee.
Results: VA and CS data were analysed with a repeated measures
ANOVA with Time (pre- vs. post-test), and Spatial Frequency
(only for CS: 0.8, 2.9, 5.8, 9.7, and 14.5 cpd) as within-subjects
factors, and Eye (amblyopic/trained vs. non-amblyopic/untrained)
as a between-subjects factor. Following eight sessions of a contrast
detection training with lateral masking, VA significantly improved in
both trained and untrained eye (F1,12=35.4, p=.0001, η2p=0.75). The
VA in the trained and untrained eye was also significantly different
(F1,8=22.12, p=.001, η2p=0.65). CS significantly improved after
training (F1,12=11.7, p=.005, η2p=0.49), regardless the eye (interaction
Time by Eye: F1,12=.03, p=.87, η2p=0.02)
Conclusions: In our small sample of participants, a short (8 sessions)
contrast detection training under lateral masking conditions and
concurrent hf-tRNS was able to increase mean VA by 0.18 LogMAR
(53% improvement, ranging from 25% to 111%) in the trained
amblyopic eye. The CSF also resulted in strong improvements
following training.
Commercial Relationships: Antonella Veronese, None; Giuseppe
Lo Giudice, None; Gianluca Campana, None; Rebecca Camilleri,
None; Andrea Pavan, None; Alessandro Galan, None
Program Number: 2194 Poster Board Number: B0047
Presentation Time: 3:45 PM–5:30 PM
A personalized approach to occlusion therapy for amblyopia
Laura Smith1, Catherine Stewart1, Alistair R. Fielder1, Merrick J.
Moseley1, Michael Wallace2. 1Optometry and Visual Science, City
University London, London, United Kingdom; 2Biostatistics, McGill
University, Montreal, QC, Canada.
Purpose: To use data of previous research in to the treatment of
amblyopia to generate a computerised model for patching strategies
to treat childhood amblyopia.
Methods: Statistical modelling analysis was undertaken on a
combined data set based on MOTAS (Stewart et al., 2004) and
ROTAS (Stewart et al., 2007) studies. We considered an approach
that aimed to prescribe a patient’s total effective occlusion dose
(TED) to be converted to a daily patching for a fixed follow-up
period. We assumed that every patient has an optimal visual outcome,
and total effective dose of occlusion which they must undertake to
achieve it.
Results: In MOTAS and ROTAS there were occlusion data for
149 participants; amblyopia associated with anisometropia in 50,
strabismus in 43, and mixed in 56 participants. Median time to
optimized visual acuity was 63 days (25% and 75% quartiles of 28
and 91 days respectively). Median visual acuity in the amblyopic
eye at start of occlusion was 0.40 logMAR (quartiles 0.22 and 0.68
logMAR). Median residual visual acuity (interocular difference)
was 0.34 logMAR (quartiles 0.23 and 0.64 logMAR). Median lower
estimate of total effective dose was 120 hours (quartiles 34 and 242
hours), median upper estimate was 176 hours (quartiles 84 and 316
hours). Exploratory plots depict a piecewise linear relationship (p =
0.008) with breakpoint estimated at 2.16 (standard error 0.51) hours/
day. The 2-part model is characterized by a steep gradient from 0
to 2.16 hours a day, followed by a shallower gradient for dose rates
above this (figure 1).
Our first model highlighted age, sex, gender, amblyopia type and
residual amblyopia as possible predictors of total effective dose.
Those with worse amblyopia at start of occlusion tended to have
a larger total effective dose. Patients who were older at start of
occlusion tended to have a lower total effective dose.
Conclusions: We have presented a new approach to the prescription
of occlusion therapy for the treatment of amblyopia in children. We
have introduced the concept of total effective dose of occlusion:
the total dose a patient requires of occlusion before it stops being
effective. Total effective dose depends on the patient’s residual
amblyopia, amblyopia type, and age at the start of occlusion therapy.
Dose-rates prescribed range from 2.5 to 12 hours/ day.
Figure 1: Average daily dose rate and (transformed) total effective
dose
Commercial Relationships: Laura Smith, None; Catherine
Stewart, None; Alistair R. Fielder, None; Merrick J. Moseley,
None; Michael Wallace, None
Support: NIHR RFPB Grant PB-PG-0808-16087
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 2195 Poster Board Number: B0048
Presentation Time: 3:45 PM–5:30 PM
A new anti-suppression approach to treating anisometropic
amblyopia
Ying Yuan1, MIN LI1, Jiangnan He2, Bilian Ke1. 1Ophthalmology,
Shanghai First People’s Hospital of Shanghai Jiaotong University,
Shanghai, China; 2Shanghai Eye Diseases Prevention & Treatment
Center, Shanghai, China.
Purpose: To evaluate the efficacy of Eyetronix Flicker Glass
therapy in treating anisometropic amblyopia by breaking interocular
suppression and promoting binocular fusion.
Methods: Thirty subjects with anisometropic amblyopia, ages 7 to
13, were enrolled in this study. A novel stimulus of Eyetronix Flicker
Glass, a lightweight spectacle frame with liquid crystal lenses that
provide direct square-wave alternating occlusion, was used at a
pre-programmed temporal frequency of 7 Hz. Visual acuity, contrast
sensitivity (CSV-1000E charts) of 3, 6, 12 and 18 cycles per degree
spatial frequencies and binocular function were measured at baseline
and follow-up visits at weeks 1, 3, 6, 9 and 12 to assess improvement
of amblyopia. In addition, pattern-reversal visual evoked potential
(RETIport32) was used to record visual cortex activity before and
after treatment.
Results: After Eyetronix Flicker Glass therapy, visual
acuity significantly improved from 0.45±0.23logMAR to
0.27±0.22logMAR. Thirteen children (48%) had two lines or more
visual acuity improvement. Contrast sensitivity of 3, 6, 12 and 18
cycles per degree spatial frequencies showed significant improvement
at the visits of 3, 6, 9 and 12 weeks. Mean stereoacuity (Titmus test)
improved from 241 seconds to 80 seconds. Stereoacuity in 11/30
children recovered to 60 seconds. In addition, there was a decreased
P100 latency and increased N75-P100 amplitude of visual evoked
potential after treatment.
Conclusions: EyeTronix Flicker Glass showed promise as an
alternative method for amblyopia treatment. It was effective in
improving both monocular and binocular function, likely by reducing
suppression and stimulating recovery of the visual cortex.
Commercial Relationships: Ying Yuan, Eyetronix.Inc (F); MIN LI,
Eyetronix.Inc (F); Jiangnan He, None; Bilian Ke, Eyetronix.Inc (F)
Support: Grant No.81200713;Grant No.12RC06;Grant No.070339
Clinical Trial: 2013-010
Program Number: 2196 Poster Board Number: B0049
Presentation Time: 3:45 PM–5:30 PM
The relationship between fusion, suppression, and diplopia in
amblyopia
Daniel P. Spiegel1, Alex S. Baldwin1, Mark A. Georgeson2, Reza
P. Farivar1, Robert F. Hess1. 1Ophthalmology, McGill University,
Montreal, QC, Canada; 2Vision Sciences, Aston University,
Birmingham, United Kingdom.
Purpose: Traditionally, it has been thought that no binocular
combination occurs in amblyopia. However, there is a growing body
of evidence that there are intact binocular mechanisms in amblyopia
rendered inactive under normal viewing conditions due to imbalanced
monocular inputs. Georgeson and Wallis (2014) recently introduced
a novel method to investigate fusion, suppression and diplopia in
normal population. We have modified this method to assess binocular
interactions in amblyopia.
Methods: Ten amblyopic and ten control subjects viewed brieflypresented (200 ms) pairs of dichoptically separated horizontal
Gaussian blurred edges. Subjects reported one central edge, one offset
edge, or a double edge as the vertical disparity was manipulated. The
experiment was conducted at a range of spatial scales (blur widths of
4, 8, 16, and 32 arc min) and contrasts. Our model, based Georgeson
and Wallis (2014), converted subjects’ responses into probabilities of
fusion, suppression, and diplopia.
Results: When the normal participants were presented equal
contrast to each eye the probability of fusion gradually decreased
with increasing disparity, as the probability of diplopia gradually
increased. In only a small proportion of the trials, normal participants
experienced suppression. The pattern was consistent across all edge
blurs. Interestingly, the majority of amblyopes had a comparable
pattern of fusion, i.e. decreasing probability with increasing disparity.
However, with increasing disparity the amblyopes tended to suppress
the amblyopic eye, experiencing diplopia only in a small proportion
of trials particularly at large blurs. Increasing the interocular contrast
offset favouring the amblyopic eye normalized the pattern of data in
a way similar to normal participants. There were some interesting
exceptions: strong suppressors for which our contrast range was
inadequate and one case in which diplopia dominated.
Conclusions: This task is suitable for assessing binocular interactions
in amblyopic participants and providing a way to quantify the
relationship between fusion, suppression and diplopia. In agreement
with previous studies, our data indicate the presence of binocular
mechanisms in amblyopia. A contrast offset favouring the amblyopic
eye normalizes the measured binocular interactions in the amblyopic
visual system.
Commercial Relationships: Daniel P. Spiegel, None; Alex S.
Baldwin, None; Mark A. Georgeson, None; Reza P. Farivar, None;
Robert F. Hess, None
Support: CIHR MOP-53346
Program Number: 2197 Poster Board Number: B0050
Presentation Time: 3:45 PM–5:30 PM
Interocular Suppression and Treatment of Childhood Amblyopia
Sarah E. Morale1, Simone L. Li1, Reed M. Jost1, Angie De La Cruz1,
David Stager3, Lori Dao3, Eileen E. Birch1, 2. 1Retina Foundation
of the Southwest, Dallas, TX; 2Dept. of Ophthalmology, UT
Southwestern Medical Center, Dallas, TX; 3Pediatric Ophthalmology
& Adult Strabismus, Plano, TX.
Purpose: New techniques for measuring depth of interocular
suppression make it possible to quantify the relationship between
suppression and monocular visual deficits in amblyopia. Here, we
investigate the effects of treatment on interocular suppression and its
relationship to changes in visual acuity in amblyopic children.
Methods: 121 children (5-12y) with strabismus, anisometropia, or
both were tested; 71 were amblyopic, 24 were never amblyopic, 26
had recovered from amblyopia with treatment. Depth of interocular
suppression was measured with a dichoptic motion coherence task.
The amblyopic eye viewed high contrast coherent moving dots
while the fellow eye viewed randomly moving dots with adjustable
contrast. Dichoptic threshold (DT) was defined as the maximum
fellow eye percent contrast (%C) that allowed reliable motion
direction discrimination determined using a 2-down-1-up staircase
protocol. Higher DT values indicate less interocular suppression.
Best-corrected visual acuity (BCVA) was measured with ATS-HOTV
(5-6y) or e-ETDRS (7-12y).
Results: Mean (± se) DT for strabismic and/or anisometropic
children who were never amblyopic was 84±3 %C and for those who
had recovered was 69±6 %C. There was no significant difference in
DT between strabismic and anisometropic amblyopia (49±5 vs 55±4
%C; p=0.36). DTs for amblyopic children being treated with glasses
(45±4 %C) and those being treated with patching + glasses (35±5
%C; p<0.0001) were significantly lower than both nonamblyopic
groups (p<0.001). DT for amblyopic children participating in
binocular treatment (Li et al Eye 2014; Birch et al JAAPOS in press)
was not significantly different from the recovered group (68±6 %C;
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
p=0.90) but was significantly higher than the patching + glasses
group (p<0.0001). For 30 children who had 2 visits, including 3
with recurrent amblyopia, 17 with stable BCVA, and 10 with BCVA
improvement, the change in DT was correlated with the change in
BCVA (r=-0.47; p=0.009).
Conclusions: The success of amblyopia treatment may rely on
the remediation of interocular suppression, which plays a key role
in strabismic and anisometropic amblyopia. Binocular treatment
appears to be more effective than patching in reducing interocular
suppression.
Commercial Relationships: Sarah E. Morale, None; Simone L.
Li, None; Reed M. Jost, None; Angie De La Cruz, None; David
Stager, None; Lori Dao, None; Eileen E. Birch, None
Support: NEI Grant EY022313
Program Number: 2198 Poster Board Number: B0051
Presentation Time: 3:45 PM–5:30 PM
Short-term monocular deprivation reveals rapid shifts in
interocular balance and gain in adult macaque visual cortex
Momotaz Begum1, 2, Daniel Y. Tso1, 2. 1Neurosurgery, SUNY Upstate
Medical University, Syracuse, NY; 2SUNY Eye Institute, Syracuse,
NY.
Purpose: Short-term monocular deprivation (STMD, patching
one eye for 2.5 hours) markedly alters interocular balance in adult
humans, as measured psychophysically (Lunghi et al 2011; Zhou et
al 2013). In those studies, the relative contribution of the patched eye
was elevated for more than an hour after patch removal. Now using
intrinsic optical imaging in anesthetized macaque primary visual
cortex (V1), we sought a parallel impact of STMD on interocular
balance as measured by the strength of the V1 ocular dominance
columns (ODC). Single-unit recordings in V1 with STMD, explored
the neural correlates of these changes interocular balance at the
neuronal level.
Methods: Optical imaging of V1 provided an initial ODC map
for the imaging studies, and to guide the placement of single-unit
electrodes. After measuring the baseline monocular and binocular
responses, one eye was “deprived” by viewing a mean gray screen
while the other eye continued to view the same stimuli and imaging
or electrophysiological recordings proceeded. This MD phase lasted
2 hours, then visual stimuli and imaging or recordings continued
another 2 hours.
Results: The imaging data were analyzed for ODC maps and for
ODC signal strength (fractional reflectance change). Single cell
responses to monocular and binocular stimuli were plotted before,
during and after STMD. During STMD, the imaging data showed a
steady decrease in the non-deprived eye strength, which dramatically
shifted course (increased) after STMD even though stimulus in
this eye was unaltered. The single-unit recordings revealed several
different types of cell responses, including cells that showed
unremarkable shifts in responses due to the STMD, other cells that
exhibited an apparent strengthening of the non-deprived eye during
STMD, and cells where the non-deprived eye showed dramatic drops
in responsivity during STMD, consistent with the observed imaging
(and psychophysical) results.
Conclusions: The weakened response for the non-deprived eye
during and immediately after patching was striking. It cannot be
explained by adaptation in the eye or cortex. We have now also
observed electrophysiologically a corresponding alteration of
interocular balance at the single cell level. These results matches the
previous psychophysical studies and suggests a dynamic mechanism
for regulating interocular balance and gain, one that is likely cortical
in origin.
Commercial Relationships: Momotaz Begum, None; Daniel Y.
Tso, None
Program Number: 2199 Poster Board Number: B0052
Presentation Time: 3:45 PM–5:30 PM
Dynamic regulation of synapsin phosphorylation by monucular
deprivaiton in mice
Tao Fu1, Qing Su1, Jing Wang1, Song Han2, Junfa Li2. 1Beijing
TongRen Eye Center, Capital Medical University affiliated Beijing
TongRen Hospital, Beijing, China; 2Department of Neurobiology
and Beijing Institute for Brain Disorders Capital Medical University,
Beijing, China.
Purpose: To investigate the dynamic changes of isoform-specific
protein expression and phosphorylation of synapsins in visual cortex
of the postnatal mice with monocular deprivation (MD).
Methods: Forty-two clean neonatal C57BL/6J mice were divided
into seven groups randomly and six for each group. The mice were
sacrificed to obtain the tissue samples at postnatal 7, 14, 21, 28, 35,
42, 60 days respectively. Similarly, Thirty neonatal healthy C57BL/6J
mice were divided into five groups randomly (Monocular Deprivation
groups, MD groups) and six for each group. The right eyelids of MD
groups were sutured at postnatal 14, 21, 28, 35, 60 days respectively,
and sacrificed after 7 days to obtain the tissue samples. Western
blot were applied to quantitatively analyze the level of Synapsin
phosphorylation and protein expression in the visual cortex.
Results: The results showed that the total (T-) protein levels of
synapsins including the isoform of Ia/b, IIa/b and IIIa were about
21-26% of adult level in visual cortex of mice at postnatal 7 days
(P7), and then the T-synapsin Ia/b and IIb could quickly reach adult
level at P35. However, the T-synapsin IIa and IIIa increased more
slowly (71-74% at P35), and then kept increasing in the visual
cortex of mice at P60. Unlike to the changes of T-synapsins, the
level of phosphorylated (P-) synapsin Ia/b (not IIa/b and IIIa) at site
1 increased with development to the highest level (286.0±16.7%)
at P21, and then decreased rapidly to a low level in visual cortex of
mice at P35-60. In addition, we found that the levels of P-synapsin
Ia/b increased significantly (p<0.05, n=6 per group) in left visual
cortex of P28 and P35 (not P21 and P42) mice with one-week MD of
right eye; and no significant changes of T-synapsins were observed
in both left and right sides of visual cortex in P21-42 mice with MD
treatment.
Conclusions: These results suggested that the isoform-specific
protein expression and site-1 phosphorylation of synapsins might
play a different role in the synaptic plasticity of visual cortex, and
monocular deprivation delays the dynamic changes of phosphorylated
synapsin Ia/b at site-1 in contralateral visual cortex of juvenile mice.
Commercial Relationships: Tao Fu, None; Qing Su, None; Jing
Wang, None; Song Han, None; Junfa Li, None
Support: NNSF of China 30600688; BNSF 7132057
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 2200 Poster Board Number: B0053
Presentation Time: 3:45 PM–5:30 PM
Effects of abnormal binocular vision due to amblyopia on early
stages of somatosensory processing
Ewa Niechwiej-Szwedo, Christina Popovich, Jessica Chin, W.
Richard Staines. Department of Kinesiology, University of Waterloo,
Waterloo, ON, Canada.
Purpose: Abnormal visual experience during development results
in amblyopia and/or strabismus and affects neural activity in the
striate and extrastriate visual areas; however, no studies to date
examined the effect of amblyopia on neurophysiological processing
beyond the primary visual areas. Previous work with healthy adults
has shown that crossmodal stimuli can modulate neural excitability
at very early stages of information processing. For example, the
amplitude of the early somatosensory event-related potential (ERP),
P50, is significantly enhanced when a tactile stimulus is presented
concurrently with a relevant visual stimulus.1 We hypothesised that
altered neural excitability in the primary visual areas in amblyopia
will alter crossmodal interactions in other brain regions.
Methods: Participants were three patients with amblyopia and five
visually-normal adults. Crossmodal interaction was investigated
during binocular viewing using EEG. Specifically, the P50
somatosensory ERP was recorded as participants engaged in a task
which required discrimination of the amplitude of a tactile and
visual stimulus. Tactile stimuli were discrete vibrations presented to
the left index finger and visual stimuli were presented as a central
horizontal bar on a computer screen. Participants executed a graded
motor response with the right hand indicating the summation of the
amplitude of the sensory inputs. Three experimental conditions were
tested: unimodal (tactile only), bimodal concurrent (tactile and visual
presented simultaneously), and bimodal priming (visual presented
100 ms prior to tactile).
Results: As hypothesized, patients showed no enhancement of the
P50 amplitude in the bimodal conditions (unimodal: 2.97±0.40μV;
bimodal concurrent: 1.86±0.84μV; bimodal priming: 1.94±0.81μV).
In contrast, visually normal participants showed a significant
enhancement of the P50 amplitude in the bimodal condition
(unimodal: 2.07±0.33μV; bimodal concurrent: 2.46±0.34μV; bimodal
priming: 3.22±0.50μV), which is consistent with the previous study1.
Conclusions: Preliminary results indicate that early crossmodal
facilitation is affected by abnormal visual experience during
development. Thus, this study offers the first evidence that the
consequences of amblyopia on neurophysiological processing extend
beyond the primary visual areas.
1
Popovich & Staines (2014) Brain Behav 4:247-60
Commercial Relationships: Ewa Niechwiej-Szwedo, None;
Christina Popovich, None; Jessica Chin, None; W. Richard
Staines, None
Support: Canadian Foundation for Innovation and Ontario Research
Fund
Purpose: The current gold standard of a successful amblyopia
treatment is the full recovery of visual acuity in the amblyopic eye.
Although anecdotal evidence suggests that other visual functions
such as contrast sensitivity might still be deficient after full acuity
recovery, there has been no systematic study on how the previously
amblyopic eye (pAE) will behave in binocular vision. In this study,
we aimed to quantify sensory dominance of the pAE in a group of
treated amblyopia.
Methods: Eight treated amblyopes with very similar acuity in
the two eyes (logMAR: .03 vs .00) participated in this study.
Stereoacuity, monocular and binocular contrast sensitivity functions
(CSF) with the quick CSF method (Lesmes et al., 2010), perceived
phase of binocularly combined sinewave grating as a function of
interocular contrast ratio (Huang et al., 2009), and pAE dominance
in viewing dichoptically presented incompatible images of equal
contrasts were measured. To quantify sensory eye dominance, we
derived three different indices: (1) binocular contrast summation
ratio: the ratio of the areas under binocular and previously fellow
eye (pFE) CSFs, (2) balance point in binocular combination: the
interocular contrast ratio at which the two eyes contribute equally to
binocular phase combination, and (3) percentage of pAE dominance.
The lower the binocular summation ratio and balance point, the
weaker the pAE relative to the pFE is; a less than 0.5 eye dominance
percentage indicates weaker pAE than pFE.
Results: Near stereo acuity (31.38”±6.93”) and pAE dominance
percentage (.5 at 1 c/d and .43 at 8 c/d) of the treated amblyopes were
largely comparable to those of normal subjects. Contrast sensitivity
remained deficient in high spatial frequencies, consistent with
Huang et al. (2007), although their binocular contrast summation
ratio (1.26±0.16) is only slightly less than that of normal subjects
(Baker et al. 2007). However, the average balance point in binocular
combination was only 0.41—-the effective contrast of images in the
pAE is equal to about 41% of the same contrast presented to the pFE
in binocular phase combination.
Conclusions: Although near stereoacuity, binocular contrast
summation ratio, and eye dominance in treated amblyopia were
normal or nearly normal, the pAE remained “lazy” in binocular phase
combination. Our results suggest that structured monocular and
binocular training are necessary to fully recover deficient functions in
amblyopia.
Commercial Relationships: Wuli Jia, None; WUXIAO ZHAO,
None; Chang-Bing Huang, None; Zhong-Lin Lu, Adaptive Sensory
Technology, LLC. (I), The Ohio State University (P)
Support: Supported by National Natural Science Foundation of
China (NSFC 31230032 and 31470983), the Knowledge Innovation
Program of the Chinese Academy of Sciences (Y3CX102003),
Institute of Psychology, CAS to Chang-Bing Huang, and NEI
(EY021553) to Zhong-Lin Lu. ZLL owns intellectual property rights
on quick CSF technology and has equity interest in Adaptive Sensory
Technology, LLC.
Program Number: 2201 Poster Board Number: B0054
Presentation Time: 3:45 PM–5:30 PM
Ocular Imbalance in Clinically Treated Amblyopia
Wuli Jia1, 2, WUXIAO ZHAO3, Chang-Bing Huang1, Zhong-Lin Lu4.
1
Institute of Psychology, Chinese Academy of Sciences, Beijing,
China; 2Institute of Psychology, University of Chinese Academy
of Sciences, Beijing, China; 3Center for Optometry and Visual
Science, The People’s Hospital of Guangxi Zhuang Autonomous
Region, Nanning, China; 4Laboratory of Brain Processes (LOBES),
Departments of Psychology, The Ohio State University, Columbus,
OH.
Program Number: 2202 Poster Board Number: B0055
Presentation Time: 3:45 PM–5:30 PM
Detection of Amblyopia using sweep VEP grating and vernier
acuity
Chuan Hou1, William V. Good1, Anthony Norcia2. 1The SmithKettlewell Eye Research Institute, San Francisco, CA; 2Department
of Psychology, Stanford University, Stanford, CA.
Purpose: Grating and vernier displacement thresholds can be
measured with swept-parameter visual evoked potentials (sVEP) and
may therefore be useful in pre- or nonverbal subjects. Psychophysical
studies indicate that while both grating and vernier acuity are
correlated with letter acuity, grating acuity underestimates the full-
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
line letter acuity loss in amblyopia. This study was conducted to
determine whether sVEP vernier acuity is better estimate of letter
acuity than is sVEP grating acuity in patients with amblyopia.
Methods: 18 adults with amblyopia (8 anisometroic and 10
strabismic) and 28 age-matched normal vision observers participated
the study. In the patient group, letter acuity was between 20/32 and
20/250 in the amblyopic eye and 20/20 or better in the fellow eye
when measured with a constant LogMar chart (Bailey-Lovie). In
the normal vision group, letter acuity was 20/20 or better in each
eye. sVEP vernier acuity was measured using square-wave gratings
containing vernier displacements modulated at 3.76 Hz. sVEP grating
acuity was measured using sine-wave gratings reversal at 7.5 Hz.
Results: As has previously been reported for psychophysical
measurements of vernier and grating acuity, sVEP vernier acuity in
both normal vision observers and amblyopic observers faithfully
reflected the absolute magnitude of the Letter acuity, while sVEP
grating acuity systematically over-estimated letter acuity in the
amblyopic eye.
Conclusions: Because sVEP venier acuity is a better estimate of
the full letter acuity loss and can be measured without the need for
instruction or behavioral responses, it may be useful in assessing
visual function in pre- and nonverbal patients.
Commercial Relationships: Chuan Hou, None; William V. Good,
None; Anthony Norcia, None
Support: The Smith-Kettlewell Eye Research Institute
Program Number: 2203 Poster Board Number: B0056
Presentation Time: 3:45 PM–5:30 PM
Normative Pediatric Data for Three Tests of Functional Vision
James R. Drover1, Shelley Cornick2, Ashley Drover2, Deanne Mayo3,
Nadine Kielly3. 1Psychology and Pediatrics, Memorial University
of Newfoundland, St. John’s, NF, Canada; 2Psychology, Memorial
University of Newfoundland, St. John’s, NF, Canada; 3Private
Practice Optometrist, St. John’s, NF, Canada.
Purpose: Tests of visual acuity, stereoacuity, and refractive error
are common components of preschool vision screening programs.
An increasing number of these tests are becoming commercially
available. The purpose of the present study is to provide the first
normative pediatric data for three such tests, namely, the Precision
Vision Visual Acuity Testing (PVVAT) system, the Pass Test 3 Stereo
Test, and the PlusoptiX S09 Vision Screener.
Methods: The participants included 267 children between the ages
of 3 and 5 years (Mean=4.2±0.8years) participating in a preschool
vision screening study. The children completed monocular testing
with the PVVAT system, a computerized test of visual acuity. The
optotypes used were isolated Patti Pics symbols surrounded by
crowding bars. Stereoacuity was assessed using the Pass Test 3
Stereo Test, a random-dot test similar to the Random Dot E Stereo
Test. Refractive error was measured using the Plusoptix S09 Vision
Screener, which provides automatic, noncycloplegic estimates of
refractive error. The mean and 95% tolerance limits were determined
for each test.
Results: Visual acuity improved significantly from 0.32 logMAR at
3 years to 0.18 logMAR at 5 years (p<0.0001). The lower tolerance
limit improved from 0.59 logMAR at 3 years to 0.38 logMAR at 5
years. Stereoacuity also improved, decreasing from 120 arcsec (lower
tolerance limit = 294 arcsec) at 3 years to 87 arcsec (lower tolerance
limit = 220 arcsec) at 5 years (p=0.0015). Spherical refractive error
remained stable at 0.27D (lower tolerance limit at 3 years = 1.33D;
lower tolerance limit at 5 years = 0.91D; p=0.81), while cylindrical
refractive error was also relatively stable, measuring 0.39D (lower
tolerance limit = 1.00D) at 3 years and 0.37D (lower tolerance limit =
0.93D) at 5 years (p=0.90).
Conclusions: Both visual acuity and stereoacuity improved
significantly from 3 to 5 years of age. Note however, the norms
obtained using the PVVAT system were somewhat lower than those
reported in previous studies using different tests. The stability of
spherical refractive error is unusual to some extent in that these
children are undergoing emmetropization, but it does agree with a
previous study providing noncycloplegic estimates of refractive error
in children.
Commercial Relationships: James R. Drover, None; Shelley
Cornick, None; Ashley Drover, None; Deanne Mayo, None;
Nadine Kielly, None
Support: Canadian National Institute for the Blind New Researcher
Award; Janeway Foundation Grant
Program Number: 2204 Poster Board Number: B0057
Presentation Time: 3:45 PM–5:30 PM
Identification of young children for participation in studies of
spectacle correction through pediatric primary care clinics: A
pilot study
Irene Campus1, Kimberly Gerhart2, Jordana M. Smith1, Amy Davis1,
Joseph M. Miller1, Erin M. Harvey1. 1Ophthal & Vision Science,
University of Arizona, Tucson, AZ; 2Pediatrics, University of
Arizona, Tucson, AZ.
Purpose: To determine the true positive rate for children referred for
eye examinations based on SPOT (Welch Allyn, Inc) photoscreening
in pediatric primary care clinics.
Methods: Children were screened at well-child checks with the
SPOT photoscreener at one of three pediatric clinics. Screening
failures were referred to the University of Arizona Visual
Development Laboratory for follow-up eye examinations which
included cycloplegic refraction and assessment of ocular alignment.
Screening results were considered true positives if examination
results met American Academy of Pediatric Ophthalmology and
Strabismus (AAPOS) amblyopia risk factor referral criteria for
children age 12 months and older.
Results: The final sample included 31 children ranging in age from
12 to 70 months who failed a SPOT screening conducted at their
pediatric primary care clinic and completed an eye examination at the
Visual Development Lab. Children failed the SPOT screening due
to suspected astigmatism (24/31, 77%), anisometropia (5/31, 16%),
hyperopia (2/31, 6%), and gaze asymmetry (2/31, 6%) (one child met
criteria for astigmatism, hyperopia and anisometropia). Of the 31
children, 16 met AAPOS referral criteria based on eye examination
results indicating a true positive rate of 52%. False positive rates
were 10/24 (42%) for astigmatism, 1/2 (50%) for hyperopia, 4/5
(80%) for anisometropia, and 2/2 (100%) for gaze asymmetry.
Conclusions: Results indicate that approximately half of the children
referred had significant refractive error. True positive referrals may
be improved if primary care clinics repeat screenings to verify
results before referring children. These preliminary data suggest that
this method may be an efficient way to recruit subjects for clinical
trials on refractive correction of young children. The primary care
recruitment base will produce a study sample of previously untreated
children that is more generalizable than samples recruited through
ophthalmology/optometry clinics.
Commercial Relationships: Irene Campus, None; Kimberly
Gerhart, None; Jordana M. Smith, None; Amy Davis, None;
Joseph M. Miller, None; Erin M. Harvey, None
Support: NIH/NEI EY13153 (EMH), Research to Prevent Blindness
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 2205 Poster Board Number: B0058
Presentation Time: 3:45 PM–5:30 PM
Refractive Change in Children with Accommodative Esotropia
Lucas Bonafede1, Lloyd Bender1, James Shaffer2, Gui-Shuang Ying2,
Gil Binenbaum1, 2. 1Ophthalmology, The Children’s Hospital of
Philadelphia, Philadelphia, PA; 2The Scheie Eye Institute, Perelman
School of Medicine at the University of Pennsylvania, Philadelphia,
PA.
Purpose: There is debate regarding the degree of change in refractive
error over time in children with accommodative esotropia. We
conducted a retrospective cohort study to determine whether there is a
measurable change in hypermetropia in children with accommodative
esotropia as they age.
Methods: We identified children with accommodative or partially
accommodative esotropia diagnosed prior to age 7 years, followed
to age 10 or older, and with at least two full cycloplegic refractions,
one performed prior to age 7 years and one after age 10 years.
Subjects who lacked refractive or orthoptic data, or had a concurrent
ocular, motility, or systemic abnormality were excluded. The primary
outcome was annual change in spherical equivalent refractive error
calculated from linear mixed effect models with assessment for
breakpoints based upon the annual changes. The annual change was
further calculated during two periods (ages 3 to 7 years and ages 7 to
15 years) with subgroup analysis by baseline refractive error less than
or greater than 4 diopters (D) of hypermetropia.
Results: 405 subjects met inclusion criteria. Mean age at first and
last visit was 3.2 (SD 1.6) and 12.1 (SD 1.9) years, respectively,
with the mean number of cycloplegic refractions being 7.6 (SD 2.5).
Between ages 3 and 7, refractive error among children with baseline
hypermetropia <4 D (n=176) increased by 0.14 D/year (95% CI
+0.10 to +0.18), while refractive error was stable among children
with baseline 4D or greater (n=229) whose annual change was
0.0 D/year (95% CI -0.03 to +0.04); the difference among groups
was significant (p<0.001). Hypermetropia decreased from age 7
to 15 years in both subgroups: <4D subgroup -0.18 D/year (-0.21
to -0.16), 4D+ subgroup -0.20 D/year (-0.22 to -0.17)(comparison
between subgroups p=0.527). There were no significant differences
in refractive change between fully (n=274) and partially (n=131)
accommodative esotropia (p>0.10).
Conclusions: Hypermetropia in children with accommodative
esotropia is stable or increases up to age 7 years. Hypermetropia
then decreases gradually between ages 7 and 15 years. However,
the decrease in refractive error is not large for the great majority of
children and is similar regardless of baseline refractive error.
Commercial Relationships: Lucas Bonafede, None; Lloyd
Bender, None; James Shaffer, None; Gui-Shuang Ying, None; Gil
Binenbaum, None
Support: NIH grants P30 EY01583-26, 5T35DK060441-10, and
UL1RR02499
Program Number: 2206 Poster Board Number: B0059
Presentation Time: 3:45 PM–5:30 PM
Vision In Preschoolers - Hyperopia In Preschoolers (VIP - HIP)
Study: Visual function differences between Hyperopes and
Emmetropes
Elise Ciner. Salus University, Elkins Park, PA.
Purpose: To compare the visual function of uncorrected
hyperopic(≥3 to ≤6 diopters [D]) and emmetropic children without
strabismus or amblyopia who were enrolled in the Vision in
Preschoolers – Hyperopia in Preschoolers study.
Methods: Participants were children 4 to 5 years old attending
preschool or kindergarten, who had never received refractive
correction. Data collection included threshold monocular visual
acuity (VA) at distance and binocular VA at near with crowded
HOTV, accommodative response by Monocular Estimation Method
(MEM) and Grand Seiko autorefraction at 33cm, and stereoacuity (up
to 30 sec arc) by Preschool Assessment of Stereopsis with a Smile
(PASS). Cycloplegic autorefraction was performed using Retinomax
to confirm the presence of either hyperopia (≥3.0D to ≤6.0D in the
most hyperopic meridian of at least one eye; astigmatism ≤1.5D and
anisometropia ≤1.0D) or emmetropia (hyperopia <1.0D; myopia,
astigmatism and anisometropia <1.0D). Cover test at distance and
near and VA were used to rule out strabismus or amblyopia.
Results: 492 children (244 hyperopes and 248 emmetropes)
participated (mean age 58 months; mean [+SD] spherical equivalent
refractive error +3.47D+0.81 in hyperopes and +0.37D+0.50 in
emmetropes). Mean logMAR distance VA was better for emmetropes
than hyperopes (0.10±0.11 vs. 0.19±0.10, p<.001) and more
emmetropes than hyperopes were able to achieve VA of at least
20/20 in the better seeing eye (53.6% vs. 21.4%, p<0.001). The
mean logMAR VA at near in emmetropes was better than hyperopes
(0.13±0.11 vs. 0.21±0.11, p<.001), with 20/20 VA attained by
23.8% of emmetropes vs. 5.3% of hyperopes (p<0.001). Mean
accommodative lag in emmetropes was smaller than in hyperopes for
both MEM (1.0±0.5 vs. 2.0±1.0, p<0.001) and Grand Seiko (0.9±0.6
vs. 1.8±1.1, p<0.001). More emmetropes (59.3%) than hyperopes
(16.4%) were able to achieve one of the two best tested stereoacuity
levels (30 or 40 sec arc, p<0.001). Mean stereoacuity was better
in emmetropes than hyperopes (67±60 sec arc vs.166±137 sec arc,
p<.001).
Conclusions: Visual function as measured with VA, accommodative
response and stereoacuity was significantly better in emmetropes
compared to uncorrected hyperopes in this group of 4 to 5 year
old children without strabismus or amblyopia. It is not known if
correction of the hyperopia at this age improves these visual skills.
Commercial Relationships: Elise Ciner, None
Support: NIH/NEI R01EY021141
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 2207 Poster Board Number: B0060
Presentation Time: 3:45 PM–5:30 PM
The Clinical Profile of Moderate Hyperopia in Children Three to
Five Years of Age
Donny W. Suh1, Marjean T. Kulp2, Trevano W. Dean3, Raymond T.
Kraker3, Sergul A. Erzurum4, 5, David K. Wallace6, Yi Pang7, Caroline
J. Shea8, John M. Avallone9. 1Department of Ophthlamology,
University of Nebraska, West Des Moines, IA; 2College of
Optometry, The Ohio State University, Columbus, OH; 3Jaeb Center
for Health Research, Tampa, FL; 4Eye Care Associates, Youngstown,
OH; 5Northeast Ohio Medical University, Rootstown, OH; 6Duke
Eye Center, Durham, NC; 7Illinois College of Optometry, Chicago,
IL; 8Providence Sacred Heart Medical Center, Spokane, WA;
9
Ophthalmology Associates of Greater Annapolis, Arnold, MD.
Purpose: To describe relationships among baseline clinical findings
in a cohort of children 3 to 5 years of age with moderate hyperopia
participating in a 3-year randomized trial comparing glasses versus
observation for development of amblyopia and strabismus.
Methods: 117 children 3 to 5 years of age with hyperopia in at least
one eye between +3.00D and +6.00D spherical equivalent (SE),
astigmatism ≤+1.50D in both eyes, and anisometropia ≤+1.50D SE
based on cycloplegic refraction were enrolled. To be eligible, children
had to have no measurable heterotropia, and could not have received
previous treatment for refractive error, amblyopia, or strabismus.
In addition, children had to 1) demonstrate age-normal monocular
visual acuity (VA) uncorrected at distance in both eyes measured
without cycloplegia, using the ATS-HOTV© VA testing protocol; 2)
have ≤1 line of interocular difference; and 3) demonstrate age-normal
stereoacuity on the Randot Preschool Stereotest. Binocular near VA
and monocular estimate method (MEM) dynamic retinoscopy were
measured in a subset of subjects. Pearson correlation and partial
correlation coefficients and 95% confidence intervals (CI) were
calculated to evaluate relationships.
Results: The mean age was 4.42 years, and mean SE refractive
error was +3.95D in the more hyperopic eye and +3.61D in the
less hyperopic eye. Greater hyperopia at baseline was associated
with greater accommodative lag as measured by MEM retinoscopy
(R=0.31, 95% CI= 0.05 to 0.53). Higher hyperopia at baseline was
associated with worse distance VA, controlling for age (R=0.24,
95% CI= 0.06 to 0.41). Better binocular near VA was associated with
better monocular distance VA controlling for age (the correlation of
near VA with distance VA was 0.35 (95% CI= 0.16 to 0.51) in the
better seeing eye and was 0.34 (95% CI= 0.15 to 0.51) in the worse
seeing eye). Better binocular near VA was also associated with better
stereoacuity (R=0.24, 95% CI = 0.04 to 0.42) controlling for age and
anisometropia.
Conclusions: Weak to moderate associations exist among children
enrolled with moderate hyperopia (+3.00D to +6.00D) and agenormal VA and stereoacuity. As expected, greater hyperopia is
moderately associated with greater accommodative lag and weakly
associated with worse distance VA. Better binocular near VA is
moderately associated with better monocular distance VA and weakly
associated with better stereoacuity.
Commercial Relationships: Donny W. Suh, None; Marjean T.
Kulp, None; Trevano W. Dean, None; Raymond T. Kraker, None;
Sergul A. Erzurum, None; David K. Wallace, None; Yi Pang,
None; Caroline J. Shea, None; John M. Avallone, None
Support: NIH Grants EY018810, EY023198, and EY011751
Clinical Trial: NCT01515475
Program Number: 2208 Poster Board Number: B0061
Presentation Time: 3:45 PM–5:30 PM
Refractive errors in a rural population of Argentine Patagonia
Julio A. Urrets-Zavalia1, Leandro Correa1, Evangelina Esposito1,
M. E. Gonzalez-Castellanos1, Dana Martinez1, fernanda Suarez2,
Horacio M. Serra2. 1University Clinic R Fabiola/Ophthalmol,
Universidad Catolica de Cordoba, Cordoba, Argentina; 2CIBICICONICET, Faculty of Chemical Sciences, Universidad Nacional de
Cordoba, Cordoba, Argentina.
Purpose: Information of refractive errors prevalence in rural
populations in Argentina is lacking. The purpose of our study was to
assess the prevalence of refractive errors in an adult rural population
living in an area of the Argentine Patagonia.
Methods: An observational, descriptive and retrospective study was
performed to assess the frequency of myopia, hyperopia, astigmatism
and anisometropia in 144 consecutive adult patients, 76 men and
68 women, of mapuche etnia from a rural region of the Argentine
Patagonia. All patients received a comprehensive eye examination,
including visual acuity with Snellen chart, and refraction was
obtained under cycloplegia. Refractive errors were evaluated in
spherical equivalent (SE). Myopia and hyperopia were defined as
spherical equivalent (SE) ± 0.50. All patients with SE less than ±
0.50D were considered as emmetropic. Astigmatism was defined as
a cylinder equal or greater than 0.50D. Anisometropia was defined
as the difference in spherical equivalent of > 1.00D between the two
eyes. Each refractive error was separated into three different groups:
low (less than 1d), moderate (1-3D) and severe (> 3d) astigmatism;
low (<+2D), moderate (+2.25 to +5D) and severe (more than+5D)
hyperopia; low (less than -3D), moderate (-3 to -6D) and severe
(more than -6D) myopia . As the Spearman correlation coefficient for
the SE and the cylinder between the right and left eye was high (r =
0.86, P <0.0001), only data from the right eye were used for analysis.
Anisometropia was analyzed with SE data of both eyes. Variables
with a p<0.05 were considered as significant.
Results: Median age was 55.5 years (r= 20-84 years). The prevalence
for emmetropia was 34% (95% CI = -0.38, 0.38); myopia 18% (95%
CI = -21.25, -0.50), being more prevalent in women (p<0.001),
much more frequently involved in near work tasks; hyperopia was
46.5% (95% CI = 0.5; 4.38); and astigmatism 63.2% (95% CI =
0.5; 5.5). Low (30.6%) and moderate (26.4%) astigmatism were
more prevalent. 86,6% of hyperopic patients had low hyperopia,
11,9% moderate and the 1,5% had severe hyperopia. Among myopic
patients 73.1% had low, 11.5% moderate and 15.4% severe myopia.
Anisometropia prevalence was 14.6% (95% CI = 1; 20.5).
Conclusions: Astigmatism, in particular low and moderate,
was found to be highly prevalent among this rural population.
Environmental factors and type of activity might contribute to
astigmatism and myopia, respectively.
Commercial Relationships: Julio A. Urrets-Zavalia, None;
Leandro Correa, None; Evangelina Esposito, None; M. E.
Gonzalez-Castellanos, None; Dana Martinez, None; fernanda
Suarez, None; Horacio M. Serra, None
Program Number: 2209 Poster Board Number: B0062
Presentation Time: 3:45 PM–5:30 PM
Comparison of non-cycloplegic refraction with the PlusOptix A09
distance refraction and cycloplegic refraction.
Arnaud Payerols1, Claudie Malrieu-Eliaou1, Max Villain1, 2, Vincent
Daien1, 2. 1Ophthalmology, Gui de Chauliac Hospital, Montpellier,
Montpellier, France; 2Montpellier 1 University, Montpellier, France.
Purpose:
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Accurate measurement of refraction in paediatric ophthalmology is
mandatory. Cycloplegic refraction is the gold standard before first
spectacle and during strabismus or amblyopia management. In this
study we aimed to identify the distance refraction values as compared
with non-cycloplegic refraction and cycloplegic refraction.
Methods:
A total of 32 children (corresponding to 64 eyes) ranging from
7 to 139 months of age where prospectively included. Before
cycloplegic administration of 1% cyclopentolate hydrochloride,
each child underwent refraction with the PlusOptix A09 and with
the Retinomax hand-held or the Nidek autorefractor when possible.
Same measurements were performed after cycloplegia. Paired t-tests
were used to compare spherical equivalent between each refraction.
Pearson coefficients were used to correlate refraction values. The
Bland-Altman method was used to assess the difference in refraction
between distance PlusOptix A09 and cycloplegic refraction. Right
eye was considered for all comparisons.
Results:
We observed significant differences of mean (interquartile range)
spherical equivalent between classic refraction (-0.70 [-2.0;1.1]
D) and PlusOptix A09 (+0.54 [-0.8;1.9] D), p=0.008 and between
spherical equivalent from PlusOptix A09 (+0.54 [-0.8;1.9] D) and
cycloplegic refraction (+1.06 [-0.4;2.0] D), p=0.02. The refraction
value with the PlusOptix A09 was positively and significantly
correlated to cycloplegic refraction (r =+0.81, p<0.001). The mean
difference between PlusOptix A09 and cycloplegic refraction was
+0.52 (IC95: 0.10 - 0.93) and the limit of agreement range from 1.55 D to +3.15 D.
Conclusions:
This study documented the spherical equivalent value of non
cycloplegic refraction performed with PlusOptix A09 that give closer
value to cycloplegic refraction than classic refraction. Distance
refraction can constitute a tool for screening or follow up that have
higher value than classical non-cycloplegic refraction. However it
cannot replace the cycloplegic refraction for first spectacle correction
and during strabismus or amblyopia management.
Commercial Relationships: Arnaud Payerols, None; Claudie
Malrieu-Eliaou, None; Max Villain, None; Vincent Daien, None
Program Number: 2210 Poster Board Number: B0063
Presentation Time: 3:45 PM–5:30 PM
Infrared photorefraction is more sensitive in the detection of
visually significant refractive errors in school children when
compared to visual acuity measurement
Minal P. Patil1, Ashwin C. Mallipatna1, Swathi Baliga1, Vasudha
Kemmanu1, Bhujang Shetty2. 1Peadiatric Ophthalmology, Narayana
Nethralaya, Bangalore, India; 2Narayana Nethralaya Foundation,
Bangalore, India.
Purpose: Refractive error is major cause of visual impairment in
school children. We intend to determine the accuracy of visual acuity
and infrared photorefraction testing in school, by comparing it to
visual acuity and cycloplegic autorefraction done in the hospital.
Methods: Retrospective data was collected from 4 schools with
1241 children (5 to 18 years) screened with visual acuity and infrared
photorefraction using the Plusoptix Autorefractor A09 (Plusoptix
GmbH, Nuremberg, Germany). Children referred for further
examination met at least one of these criteria: 1. Vision worse than
6/12; 2. Refractive spherical equivalent lesser than -0.5D (myopia) or
greater than +3.0D (hypermetropia); 3. Cylindrical error greater than
2.5D; 4.Any complaint or obvious eye pathology. Of the children
who were referred for further examination, the following was done in
clinic:1. Visual acuity; 2. Cycloplegic autorefraction.
Results: Of the 1241 children listed in the schools 133 were absent.
Visual acuity was recorded in 2071 eyes of which 92 eyes were worse
than 6/12. Visual acuity was rechecked in clinic for 73 eyes and 28
were found to have vision of 6/12 or better .Of the 1108 children
screened, 17 children were referred for vision complaints. Of the
2216 eyes screened, refraction was recorded using the photorefractor
in 1892 eyes. The device was not able to get readings in 197 eyes.
Myopia worse than -0.50D was seen in 100 eyes, hypermetropia
worse than +3.00D was seen in 22 eyes and a cylindrical refractive
error greater than 2.5D was seen in 46 eyes. Sensitivity and
specificity data was calculated using the limits of our screening
criteria. Visual acuity measurements alone in school screening were
42% sensitive and 93% specific. The photo refractor prediction of
myopia worse than -0.5D was 62% sensitive and 84% specific, that
for hypermetropia worse than +3.0D was 100% sensitive and 95%
specific, and that for cylinder worse than 2.5D was 100% sensitive
and 93% specific.
Conclusions: During school screening, visual acuity measurement
alone may not be sensitive enough to detect poor vision.
Photorefraction can help detect significant refractive errors with
reasonable accuracy. However, careful selection of screening criteria
is important to be most sensitive and specific for the population
screened.
Commercial Relationships: Minal P. Patil, None; Ashwin C.
Mallipatna, None; Swathi Baliga, None; Vasudha Kemmanu,
None; Bhujang Shetty, None
Program Number: 2211 Poster Board Number: B0064
Presentation Time: 3:45 PM–5:30 PM
Validation of Confidence Levels for a Cell Phone-Based Refractor
(NETRA-G)
Vitor F. Pamplona1, Steven Turpin2, Jorge Cuadros2, Rahul Modi1.
1
EyeNetra Inc, Somerville, MA; 2University of California, Berkeley,
Berkeley, MA.
Purpose: To assess the performance of a cell phone based refracting
device (NET). We identify the efficacy of NET confidence values
by comparing refractive differences between NET and subjective
refraction (SR).
Methods: NET retrofits a high-resolution mobile phone (Samsung
S4) by adding a pinhole mask and a lens onto the display. The
device is bi-ocular and both eyes are constantly fogged (+6D).
The subject aligns red and green lines with the translation on the
screen proportional to refractive error. Besides refraction, the
device computes a confidence value (from 0, poor, to 1, good).
The hypothesis is that results under 0.4 require a retest. 89 subjects
(mean + SD age 28.41 +/- 6.95) underwent SR and NET refraction.
Auto-Refractor (AR) was used as a starting point for SR. Subjects
were split according to NET’s confidence value and compared. Group
A (n=70) included high confidence readings (>0.4) and Group B
(n=19) low confidence readings (<0.4). Subject’s refractive error
ranged from +1.50 to -8.25D (mean + SD refraction -1.37 +/- 1.90D).
Exclusion criteria included: amblyopia, non-refractory pathologies,
and 4 subjects in which NET yielded a better refraction than SR.
Results: For all 89 subjects, the mean + SD Vector Power Difference
(VDD) of NET-SR is 1.20 +/- 1.24D. Group A’s mean + SD VDD
is 0.95 +/- 0.60D (corr=95%). In comparison, the mean + SD VDD
of AR-SR is 0.51 +/- 0.45D (note: SR is biased towards AR). NET,
AR and SR yielded 20/25 or better vision on 92%, 96% and 98%
respectively. Mean + SD visual acuity difference of NET-SR is -0.07
+/- 0.08 logMar. Group B’s mean + SD VDD of NET-SR is 2.12 +/2.18D (corr=65%). NET, AR and SR yielded 20/25 or better for 61%,
72% and 89% respectively. Linear regression of spherical equivalent
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
presented a slope of 0.86 and a y-intercept of -0.63D. Mean + SD of
PD difference of NET-AR is -0.76 +/- 1.88mm.
Conclusions: NET’s confidence value can be used as a predictor
for insufficient accuracy, triggering a retest or a discarding method.
The low confidence group included the only 2 subjects with highorder aberrations and 5 subjects that required translation (a known
language barrier for NET, since subjects need to understand the
procedures). Group A included all subjects that could not reach 20/20
vision on the SR. The results show that NET has potential to be a
used as an effective tool for rapidly estimating refractive errors and
interpupillary distance measurements.
Commercial Relationships: Vitor F. Pamplona, EyeNetra Inc
(E); Steven Turpin, None; Jorge Cuadros, None; Rahul Modi,
EyeNetra Inc (E)
Program Number: 2212 Poster Board Number: B0065
Presentation Time: 3:45 PM–5:30 PM
Spatial summation of perimetric stimuli across the visual field in
anisometropic and strabismic amblyopia
Shindy Je, Fergal A. Ennis, James E. Morgan, Tony Redmond. School
of Optometry and Vision Sciences, Cardiff University, Cardiff,
United Kingdom.
Purpose: To investigate differences in the area of complete spatial
summation (Ricco’s area) for standard perimetric stimuli, between
amblyopic eyes and their fellow non-amblyopic eye, and to compare
any such inter-ocular differences to those in observers with normal
binocular vision.
Methods: Achromatic contrast detection thresholds were measured
with circular incremental stimuli of different area (Goldmann I-V;
0.02°–1.7° diameter) at 12 visual field locations (9°, 15° and 21°
eccentricity; 4 locations each) in observers with strabismic amblyopia
(n=2; age: 19, 23 years), anisometropic amblyopia (n=3; age:18, 19,
20 years), and normal binocular vision (n=5; mean age: 25.8 years,
range: 20, 31). Background luminance was 10cd/m2. Experiments
were performed on an Octopus 900 perimeter (Haag Streit, Koeniz,
Switzerland), with the Open Perimetry Interface. Thresholds were
averaged by eccentricity and three spatial summation curves were
constructed for each eye. Ricco’s area was estimated from each by
two-phase regression analysis. Estimates were compared between
amblyopic and fellow non-amblyopic eyes at each eccentricity.
Inter-ocular differences at each eccentricity were compared between
observers with and without amblyopia.
Results: Ricco’s area was significantly larger (mean: 0.3 log
deg2) in amblyopic eyes than in fellow non-amblyopic eyes at all
eccentricities (p=0.01, paired t-test, Holm-Bonferroni correction).
Inter-ocular differences in control subjects (mean: 0.03 log deg2) were
not statistically significant (p>0.05, paired t-test, Holm-Bonferroni
correction). Compared with control eyes, mean Ricco’s area was
larger in amblyopic eyes but smaller in non-amblyopic eyes (Figure).
Conclusions: Given that changes in receptive fields of retinal
ganglion cells in amblyopia are not marked, our findings likely
point to a difference in representation of each eye at the cortical
level. Greater convergence of signals from retinal ganglion cells in
amblyopic eyes to thinner ocular dominance (OD) columns in V1,
and less convergence from those in the fellow non-amblyopic eye
to thicker OD columns, may explain these results. These findings
also support the concept that the physiological basis for Ricco’s
area reflects processing along the entire visual pathway, and is not
confined to the retina.
Mean Ricco’s area as a function of eccentricity in amblyopic, nonamblyopic and control eyes. (Error bars: SEM)
Commercial Relationships: Shindy Je, None; Fergal A. Ennis,
None; James E. Morgan, None; Tony Redmond, Heidelberg
Engineering (F)
Support: College of Optometrists Research Fellowship
Program Number: 2213 Poster Board Number: B0066
Presentation Time: 3:45 PM–5:30 PM
Do different mechanisms mediate contour interaction and
crowding in the fovea and visual periphery?
Stephanie M. Marten-Ellis, Harold E. Bedell. College of Optometry,
University of Houston, Houston, TX.
Purpose: To compare the influence of nearby flanking lines (contour
interaction) and flanking letters (crowding) on the identification of
foveal and peripheral letters at different luminances.
Methods: Single Sloan letters were presented at the fovea or at 5
deg in the inferior visual field, with and without 4 flanking bars or
flanking letters placed symmetrically to the right, left, above and
below the target letter. Background luminance was either 200 or
0.5 cd/sq.m. For each combination of eccentricity and background
luminance, letter size was adjusted to produce 80 – 90% correct
identification when the flanking targets were absent. Percent correct
letter identification was then determined for 5 to 8 edge-to-edge
separations between the flankers and Sloan letters in 2 normal
observers. The bar flankers subtended 1 x 5 letter-stroke widths and
the letter flankers had the same dimensions as the letter targets.
Results: At the fovea, the extent of interaction (the maximum
target-to-flanker separation that influenced performance) was
approximately 3 – 4 min arc for both bar and letter flankers. The
magnitude of interaction (the maximum reduction of percent correct
letter identification) also was similar for both types of flankers,
but decreased dramatically at low compared to high background
luminance. At 5 deg in the inferior field, the extent of contour
interaction for bar flankers was approximately 4 times smaller than
the extent of crowding for letter flankers. Reducing background
luminance had no effect on either the extent or the magnitude of
peripheral contour interaction or crowding.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Conclusions: At the fovea, bar and letter flanking targets interfere
with letter recognition based on the same luminance-dependent
mechanism. In the periphery, contour interaction and crowding are
independent of background luminance but flanking bars impair
identification much less strongly than flanking letters. The results
suggest that flanking targets influence foveal and peripheral letter
identification by different mechanisms.
Commercial Relationships: Stephanie M. Marten-Ellis, None;
Harold E. Bedell, None
Support: NEI Grant T35 EY007088
Program Number: 2214 Poster Board Number: B0067
Presentation Time: 3:45 PM–5:30 PM
Crowding in simulated monovision
Zuopao Zhuo1, 2, Hua Bi2, Bin Zhang2, Ziming Liu3, 2, Zheyi Chen1,
Binbin Su1, Jun Jiang1, Fan Lv1. 1Optometry Department, The
Affiliated Eye Hospital of Wenzhou Medical University, Wenzhou,
China; 2College of Optometry, NOVA Southeastern University,
Davie, FL; 3Shenyang He Eye Hospital, Shenyang, China.
Purpose: Monovision is the presbyopic vision correction practice
of prescribing distance vision in one eye and near vision in the other
eye. With blurred image in one eye and clear image in the other, the
visual system experiences more binocular masking/suppression/
rivalry. About 20%-30% patients with monovision have reported
discomfort, indicating certain impairment in visual function. The
largely normal visual acuity, which represents the foveal visual
function, indicates periphery visual disturbance in those patients.
Crowding refers to the reduced object identification ability in the
periphery when the target object is flanked by distracters. It is a
binocular process and other binocular processes that are ongoing
simultaneously could interfere to amplify the impairment to object
identification. In this study, we tested whether crowding is much
more severe in simulated monovision condition.
Methods: 20 subjects participated in this study. Cycloplegia was
induced by instillation of one drop of 1% tropicamide and an artificial
pupil with 3mm diameter was applied. Monovision was simulated
by full correction in one eye and correction with +2.5 D defocus in
the other eye. The crowding effect was quantified by reduction in
accuracy when identifying letters (5° eccentricity from the fixation)
with flankers at 5 different spacing (0.44°, 0.88°, 1.32°, 1.76°, 2.4°)
as compared with no flanker. For each subject, the crowding effect
was measured both in normal and simulated monovision condition.
Accuracy of letter identification and area of error identification
were calculated. Z-test was applied to test if the accuracy of letter
identification and area of error identification changed significantly in
simulated monovision condition.
Results: The accuracy of letter identification, when tested without
flankers, was similar in normal and simulated monovision condition.
However, with flankers, the accuracy of letter identification was
significantly lower in simulated monovision condition at all spacing
(P < 0.05), and the changes of accuracy between them at 5 different
spacing were significantly different. (P < 0.05) The area of error
identification was significantly higher in simulated monovision
condition (3.32 ± 0.47) as compared with normal condition (2.31 ±
0.59). (P < 0.05)
Conclusions: The crowding was much more severe in simulated
monovision condition than normal viewing condition, and the
difference was dependent of the spacing between the target and
flankers.
Commercial Relationships: Zuopao Zhuo, None; Hua Bi, None;
Bin Zhang, None; Ziming Liu, None; Zheyi Chen, None; Binbin
Su, None; Jun Jiang, None; Fan Lv, None
Support: NSU Health Professions Division Grant
Program Number: 2215 Poster Board Number: B0068
Presentation Time: 3:45 PM–5:30 PM
Digital self-assessment application for identifying ADHD
symptoms
Oren Yehezkel, Anna Sterkin, Maria Lev, Uri Polat. Scientific,
Eyekon E.R.D Ltd, Ramat-Gan, Israel.
Purpose: ADHD is a common neurobehavioral disorder. ADHD
is diagnosed by clinicians using subjective tools, sometimes
supported by a computerized test. However, since this diagnosis
requires visiting a clinic and is affected by external factors such as
intelligence and fatigue, many cases remain undiagnosed through
adulthood. There is a societal burden associated with undiagnosed
ADHD, creating a need for objective tools for ADHD preliminary
self-assessment, prompting seeking professional clinical diagnosis if
relevant.
Here we aimed at testing whether we can manipulate spatial and
temporal stimulation to identify ADHD symptoms in adults. To
this end, we used a short, self-administered tool based on dynamic
crowded visual stimulation to identify ADHD symptoms. Various
studies demonstrated the usefulness of crowded conditions for
measuring visual performance in aging adults and children.
Methods: Measurements using a prototype dynamic digital
assessment tool, currently developed by GlassesOff™, on
smartphones, which reliably measure functional near visual acuity
(VA), were compared between diagnosed-ADHD and control groups:
24 ADHD subjects (aged 16-28 years, with an ADHD diagnosis
performed by a neurologist or psychiatrist) and 18 controls (aged
20-30 years), all corrected to normal vision (worst binocular VA 0.04
logMAR). Stimuli consisted of matrices composed of 25 letters “E”
(5×5), each with a randomly chosen orientation having 4 options.
Two variations of inter-letter-spacing within the matrix were used
(0.4 and 1 letter size). Participants were requested to identify the
orientation of the central letter. VA thresholds were determined
using a staircase measuring the minimal detectable letter size, under
crowding conditions and the stimulus presentation ranged from 34 to
120 msec.
Results: Despite normal VA on the clinical static ETDRS chart, our
self-administered test showed a large and significant VA reduction
in ADHD subjects compared with controls: 62, 79, and 64% for 34,
60, and 120 msec, respectively, equivalent to about 2 ETDRS lines.
Similar results were obtained for 0.4-letter spacing.
Conclusions: Our self-administered dynamic digital tool may be
used for objective assessment of ADHD symptoms. We suggest that
under-development of visual functions, which is present in children
under regular conditions, persist in adults with ADHD symptoms
and that this becomes apparent under spatial and temporal loading
conditions.
Commercial Relationships: Oren Yehezkel, Eyekon ERD (E);
Anna Sterkin, Eyekon ERD Ltd (E); Maria Lev, Eyekon ERD Ltd
(E); Uri Polat, Eyekon ERD Ltd (P)
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
278 Idiopathic intracranial hypertension and papilledema
Monday, May 04, 2015 3:45 PM–5:30 PM
Exhibit Hall Poster Session
Program #/Board # Range: 2228–2239/B0081–B0092
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Contributing Section(s): Multidisciplinary Ophthalmic Imaging
Program Number: 2228 Poster Board Number: B0081
Presentation Time: 3:45 PM–5:30 PM
The relationship between the levonorgestrel-releasing
intrauterine system and idiopathic intracranial hypertension
Ruju Rai1, Brian Kirk1, Jessica Sanders2, Reuben Valenzuela1,
Subhashree Sundar1, Judith Warner1, Kathleen B. Digre1, Balamurali
Ambati1, Alison V. Crum1, Bradley J. Katz1. 1Ophthalmology & Visual
Sciences, John A. Moran Eye Center, University of Utah, Salt Lake
City, UT; 2Obstetrics and Gynecology, University of Utah, Salt Lake
City, UT.
Purpose: Unconfirmed reports have linked the levonorgestrelreleasing intrauterine system (LNG-IUS), a long-acting contraceptive,
to idiopathic intracranial hypertension (IIH). In this pilot case-control
study, we compared LNG-IUS exposure between a cohort of patients
with IIH and an analogous cohort of patients without IIH.
Methods: A retrospective series of 473 patients with ICD-9 codes
for pseudotumor cerebri (PTC) was screened for female gender, age
at onset of 18-55, diagnosis from 2008-2013, and non-idiopathic
etiologies. Of 176 eligible participants, 59 completed telephone
birth control histories of the 3 month timeframe preceding IIH onset.
Records were then queried for CPT codes for LNG-IUS insertion in
220,904 women without ICD-9 codes for PTC who were aged 18-55
and had at least one clinical encounter from 2008-2013. Descriptive
statistics and significance tests were performed, and odds ratios were
calculated.
Results: Exposure to an LNG-IUS was significantly associated with
the development of IIH (OR 7.7, 95% CI 3.2-16.4, p<0.001); the
prevalence of IIH was 0.18% in the LNG-IUS population (8/4408,
95% CI 0.07-0.35) versus 0.02% in the non-LNG-IUS population
(51/216555, 95% CI 0.01-0.03). Of those IIH patients not on an
LNG-IUS, 9 (15%) were on another contraceptive and 42 (71%) were
not on any contraceptives. All LNG-IUS users who developed IIH
manifested symptoms while the device was still in situ. There were
no significant differences between LNG-IUS users and non-users
in terms of age, body mass index, recent weight gain, or presenting
signs and symptoms.
Conclusions: Our findings suggest that LNG-IUS exposure does not
alter the clinical features of IIH; however, it is disproportionately
more common among IIH patients than non-IIH patients. Therefore,
although a causative role for LNG-IUS has not yet been established,
we recommend augmenting the routine evaluation of IIH with a birth
control history. IIH patients who are considering options for birth
control should be counseled about the possible connection between
LNG-IUS and IIH. While the preliminary evidence does not warrant
the removal of an LNG-IUS in a typical IIH patient, atypical IIH
patients (i.e. non-obese, having no other risk factors) with an LNGIUS may wish to switch to an alternative contraceptive.
Commercial Relationships: Ruju Rai, None; Brian Kirk, None;
Jessica Sanders, None; Reuben Valenzuela, None; Subhashree
Sundar, None; Judith Warner, None; Kathleen B. Digre, None;
Balamurali Ambati, None; Alison V. Crum, None; Bradley J.
Katz, None
Support: Supported in part by grants from the Center for Clinical
and Translational Sciences (8UL1TR000105) and the Research to
Prevent Blindness, Inc., New York, NY.
Program Number: 2229 Poster Board Number: B0082
Presentation Time: 3:45 PM–5:30 PM
Sixth nerve palsy in pediatric idiopathic or secondary
intracranial hypertension
Julia E. Reid1, Rachel E. Reem2, Shawn Aylward2, David Rogers2.
1
The Ohio State University, Columbus, OH; 2Nationwide Children’s
Hospital, Columbus, OH.
Purpose: To report the incidence and describe the characteristics
of sixth cranial nerve (CN VI) palsy in pediatric patients with
intracranial hypertension (IH).
Methods: A retrospective chart review of central Ohio children
diagnosed with IH over the 3-year period from 2010 to 2013 was
conducted. IH without identifiable cause was defined as idiopathic
intracranial hypertension (IIH), while IH with identifiable pathologic
etiology was deemed secondary intracranial hypertension (SIH). A
subset of patients with CN VI palsy was identified. Data collected
included patient age, gender, past medical history, etiology of SIH,
ophthalmic exam, lumbar puncture results, neuroimaging results, and
response to treatment.
Results: Seventy-nine children with intracranial hypertension were
included in the study. Ten (13%) children (4 males, 6 females; median
age 15, range 3-18) were found to have a unilateral (n=3) or bilateral
(n=7) CN VI palsy. Six children had IIH; the remaining four had SIH
from cerebral venous sinus thrombosis (n=3) and rocky mountain
spotted fever (n=1). The mean opening pressure for these patients
was 40 cm H20 (range: 21-65 cm H20). Papilledema was present
in 9/10 (90%) patients. One patient required a lumboperitoneal
shunt and two required optic nerve sheath fenestrations in addition
to medical management. All cases of CN VI palsy resolved with
treatment.
Conclusions: In our primary service area, the incidence of CN VI
palsy is 13% amongst pediatric IIH and SIH patients. The majority
of cases of CN VI palsy occur concurrently with papilledema and
commonly resolve with treatment of intracranial hypertension.
Commercial Relationships: Julia E. Reid, None; Rachel E. Reem,
None; Shawn Aylward, None; David Rogers, None
Support: The Ohio Lions Eye Research Foundation
Program Number: 2230 Poster Board Number: B0083
Presentation Time: 3:45 PM–5:30 PM
Structure function relationships in idiopathic intracranial
hypertension
Heather Moss, J Jason McAnany, Jason C. Park. Ophthalmology and
Visual Sciences, University of Illinois at Chicago, Chicago, IL.
Purpose: To establish the relationships between measures of
visual function (standard automated perimetry (SAP)), ganglion
cell function (the photopic negative response (PhNR)), ganglion
cell structure and optic nerve structure in idiopathic intracranial
hypertension (IIH).
Methods: Visual function was assessed using SAP mean deviation
(SAP-MD) scores in 10 subjects with IIH (3 untreated, 4 active,
3 treated). The PhNR of the photopic full-field, brief flash
electroretinogram, was recorded using standard stimulation and
recording techniques. Ganglion cell structure was assessed using
ganglion cell complex volume (GCCV) in a 3mm diameter region
centered on the macula, which was semi-automatically segmented
from OCT B-scans (Spectralis). Optic nerve structure was
categorized according to Frisén papilledema grading scale (FPG).
Associations within and between functional markers (SAP-MD,
PhNR) and structural markers (GCCV, FPG) were studied with
multiple linear regression (LR).
Results: Log PhNR amplitude and SAP-MD were modestly
correlated (Pearson correlation, r = 0.78, p= 0.008, LR). GCCV
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
and FPG were not associated (p=0.10, mann-whitney rank sum).
SAP-MD was associated with GCCV (r=0.72, p=0.019, LR).
Addition of FPG did not improve the LR model for SAP-MD. Log
PhNR amplitude was also associated with GCCV (r=0.77, p=0.009,
LR). Addition of FPG improved the LR model for PhNR (r=0.94,
p<0.0001, p(GCCV)<0.0001, p(FPG)=0.003, LR).
Conclusions: Though visual and ganglion cell functional markers
are modestly correlated, we find their individual correlations with
structural markers to differ. Both SAP-MD and PhNR are related to
ganglion cell atrophy, but only PhNR is also associated with degree
of acute optic nerve pathology. The observation that high-grade
papilledema is associated with PhNR decrease but not SAP-MD
severity supports literature implicating PhNR association with preperimetric optic nerve injury. Further studies are needed to determine
the clinical utility of PhNR as a marker for diagnosis and monitoring
of IIH.
Support: Unrestricted departmental grant from Research to Prevent
Blindness, Illinois Society for the Prevention of Blindness, NIH K23
EY-024345, NIH P30 EY-001792, R00 EY019510, K12 EY021475
Program Number: 2231 Poster Board Number: B0084
Presentation Time: 3:45 PM–5:30 PM
Correlation of opening pressure and Frisén grade of papilledema
in pediatric patients with intracranial hypertension
Laura L. Scott1, Shawn Aylward2, 3, David Rogers4, 5, Rachel E. Reem4,
5 1
. The Ohio State College of Medicine, Columbus, OH; 2Neurology,
Nationwide Children’s Hospital, Columbus, OH; 3Neurology, The
Ohio State University Wexner Medical Center, Columbus, OH;
4
Ophthalmology, Nationwide Children’s Hospital, Columbus, OH;
5
Ophthalmology, The Ohio State University Wexner Medical Center,
Columbus, OH.
Purpose: While clinicians are diagnosing idiopathic and secondary
intracranial hypertension in pediatric patients with increasing
frequency, a paucity of research regarding the diagnosis and clinical
features of these conditions exists. We performed a retrospective
chart review of pediatric patients with intracranial hypertension in
order to examine the relationship between lumbar puncture opening
pressure (LPOP) and the severity of papilledema grade utilizing the
Modified Frisén Scale (MFS).
Methods: 130 patients presenting between 2007 and 2013 with
lumbar puncture-confirmed intracranial hypertension were included
in the study. Demographic data and exam findings from initial exam
with an ophthalmologist were collected. The worse papilledema
grade between the two eyes on initial exam was compared to LPOP
using Spearman’s Rank Correlation Coefficient, “r.” A second reader
rated the subjects’ fundus photos and the inter-rater reliability was
calculated using Cohen’s chance-corrected kappa statistic, “k.”
Results: Of the 130 included patients, 78 were female and 52 were
male. The mean age of patients evaluated was 12.3 years old (range
3-18). 39 subjects were diagnosed with secondary intracranial
hypertension. Seventy four patients had their lumbar puncture
performed on the same day as their eye exam. A statistically
significant moderately positive correlation was found between LPOP
and Frisén grade of papilledema (r=0.426, p-value=0.000153). Even
including those whose LP and eye exam were performed on different
days, there was a weakly positive correlation between the LPOP and
papilledema grade (r=0.255, p-value of 0.003371). In addition, 236
optic disc photos of 119 patients were reviewed. The linear weighted
kappa value indicating inter-rater reliability indicated a good strength
of agreement (k=0.669).
Conclusions: In pediatric patients with intracranial hypertension, the
severity of papilledema correlates positively with lumbar puncture
opening pressure. This result confirms the findings of a recent
study in adult patients1 and may be helpful in guiding the clinical
management of patients afflicted with intracranial hypertension.
References
1. Kupersmith M. Baseline OCT Measurements in the Idiopathic
Intracranial Hypertension Treatment Trial: Part II. Correlations and
Relationship to Clinical Features. Investigative ophthalmology &
visual science. 2014-11-04.
Commercial Relationships: Laura L. Scott, None; Shawn
Aylward, None; David Rogers, None; Rachel E. Reem, None
Support: Ohio Lions Eye Research Foundation
Visual function (top) and Photopic negative response (bottom) as a
function of ganglion cell complex volume (line) and papilledema
grade (markers) in IIH subjects
Commercial Relationships: Heather Moss, None; J Jason
McAnany, None; Jason C. Park, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 2232 Poster Board Number: B0085
Presentation Time: 3:45 PM–5:30 PM
Changes in basement membrane opening displacement within
1 hour following intracranial pressure lowering in subjects with
and without idiopathic intracranial hypertension
Gautam Vangipuram, Heather Moss. University of Illinois, Chicago,
IL.
Purpose: Changes in basement membrane(BM) contour in the
region of the optic nerve head are a promising marker for intracranial
pressure(ICP) changes in idiopathic intracranial hypertension(IIH)
based on studies showing change following surgical and medical
treatment for elevated ICP. Rapid changes in BM configuration
associated with ICP lowering have yet to be studied. This study tests
the hypothesis that changes in BM opening(BMO) displacement, a
surrogate for BM contour, occur rapidly following ICP lowering via
lumbar puncture (LP).
Methods: Within 1 hour prior to and following LP in seven (27-60
yrs old, 11-24mL CSF drained) prospectively recruited subjects, 20o
OCT B-scan images centered on the right optic nerve head along
the nasal/temporal axis were acquired. The BM and inner limiting
membrane(ILM) were automatically segmented and manually
corrected. Optic nerve head maximum nasal, temporal and cup
thicknesses were calculated as the distance between the BM and ILM.
BMO displacement was calculated at the nasal and temporal margins
of the BMO referenced to a straight line between the outer nuclear
layer-inner segment junction 3 mm nasally and temporally from the
optic nerve head(fig.). Based on LP opening pressure(OP), subjects
were grouped as IIH (n=3, OP 28-55cm H2O, all with papilledema)
or non-IIH (n=4, OP 10-20cm H2O, none with papilledema).
Results: Across all subjects, BM displaced posteriorly following
LP (p=0.018 nasal, 0.063 temporal, Wilcoxan signed ranks(WSR)).
Optic nerve thicknesses and cup depth did not change following
LP (p=0.15, 0.87, 0.18, WSR). IIH subjects had greater optic nerve
thicknesses, shallower cup depth, and a more anterior BMO prior
to LP than non-IIH subjects (p=0.034 for all, Mann Whitney Rank
Sum). IIH and non-IIH subjects did not differ in the pre-post LP
change in BM displacement, optic nerve thickness or cup depth.
Groups did not differ by age or amount of CSF drained.
Conclusions: Changes in BMO displacement occur within 1 hour
of ICP lowering via LP in subjects with and without IIH. Changes in
optic nerve head contour do not occur within 1 hour of ICP lowering
in subjects with or without IIH. These observations align with reports
of BMO changes preceding optic nerve changes in treated IIH and
support the candidacy of BMO displacement as a non-invasive rapid
marker of ICP changes.
Program Number: 2233 Poster Board Number: B0086
Presentation Time: 3:45 PM–5:30 PM
Change in the Deflection of the Neural Canal Opening Over
Time with Acetazolamide Treatment in Idiopathic Intracranial
Hypertension
Jui-Kai Wang1, Patrick A. Sibony2, Randy H. Kardon4, 5, Mark
J. Kupersmith3, Mona K. Garvin5, 1. 1Department of Electrical
and Computer Engineering, The University of Iowa, Iowa City,
IA; 2Department of Ophthalmology, State University of NY at
Stony Brook/UHMC, Stony Brook, NY; 3Department of NeuroOphthalmology, Roosevelt Hospital and NYEE, New York, NY;
4
Department of Ophthalmology and Visual Sciences, The University
of Iowa, Iowa City, IA; 5Center for the Prevention and Treatment of
Visual Loss, Iowa City VA Health Care System, Iowa City, IA.
Purpose: In papilledema, Bruch’s membrane (BM) bordering the
neural canal opening is often deflected inward toward the vitreous
in contrast to normal eyes (Sibony et al., IOVS, 2011, 2014). We
prospectively compared OCT-derived changes in the BM shape with
acetazolamide (ACZ) plus diet compared to placebo plus diet in
the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).
A novel semi-automated method for quantifying the BM shape was
developed for this purpose.
Methods: For each of the 126 subjects enrolled in the OCT substudy
of the IIHTT (OCT Sub-Study Committee, IOVS, 2014), the central
slice from the Cirrus OCT high-definition (HD) 5-line raster scan at
baseline, 3 months, and 6 months (as available) was used to perform
the statistical shape analysis. After manually marking the two Bruch’s
membrane opening points in each slice, 9 landmark points were
automatically placed along Bruch’s membrane on each side of the
neural canal border, extending out radially for 2500 microns (Fig. 1).
Principal component analysis was used to create a shape model using
the landmark points at baseline. The second principal component
coefficient, reflecting the angle and direction of the neural canal
border, was then computed at each time point for study eyes in the
two treatment groups.
Results: In this analysis, 73 out of 126 subjects in IIHTT OCT
substudy had 5-line raster data available at all time points for the
study eye. In the ACZ plus diet group (n=39), the neural canal shape
measure became more positive (deflecting away from the vitreous
cavity, Fig. 2 left) over time and was significantly greater (p < 0.01)
than in the placebo plus diet group (n=34), as shown in Fig. 2. The
mean neural canal shape measure changes from baseline to 3 months
were 0.64 ± 1.10 in the ACZ group vs. -0.04 ± 0.93 in the placebo
group; from baseline to 6 months, the changes were 0.87 ± 1.26 in the
ACZ group vs. 0.03 ± 0.83 in the placebo group.
Conclusions: Displacement of the neural canal border at the optic
nerve head reflects the translaminar pressure differential between the
retrolaminar and intraocular fluid compartments and appears to be a
biomarker of successful treatment of raised intracranial pressure.
Commercial Relationships: Gautam Vangipuram, None; Heather
Moss, None
Support: Unrestricted departmental grant from Research to Prevent
Blindness, Illinois Society for the Prevention of Blindness, NIH K23
EY-024345, NIH P30 EY-001792
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Fig. 1. Semi-automated landmark placement
Fig. 2. Left: Neural canal shape model variations; Right: Shape
measure in ACZ/placebo group at baseline, 3 months and 6
months
Commercial Relationships: Jui-Kai Wang, None; Patrick A.
Sibony, None; Randy H. Kardon, Acorda (C), Department of
Veterans Affairs Research Foundation, Iowa City, IA (S), Fight for
Sight Inc (S), Novartis (C); Mark J. Kupersmith, None; Mona K.
Garvin, The University of Iowa (P)
Support: U10 EY017281-01A1, U10 EY017387-01A1,
3U10EY017281-01A1S1, R01 EY023279
Clinical Trial: NCT01003639
Program Number: 2234 Poster Board Number: B0087
Presentation Time: 3:45 PM–5:30 PM
Pointwise Visual Field Change in the Idiopathic Intracranial
Hypertension Treatment Trial
Michael Wall1, Gideon Zamba2. 1Neurology & Ophthalmology, Univ
of Iowa, Carver Coll of Med, Iowa City, IA; 2Biostatistics, University
of Iowa, Iowa City, IA.
Purpose: The Idiopathic Intracranial Hypertension Trial (IIHTT)
showed acetazolamide provided a modest but significant
improvement in global visual field function using mean deviation.
Here, we aim to further analyze 1) the rate and 2) the magnitude of
individual visual field test location change in the treatment groups
from baseline to primary end point (six months).
Methods: We evaluated 121 of the enrolled IIH subjects who had
visual field testing at baseline, six months and 3 of 4 interim visits.
At entry the SITA Standard 24-2 mean deviation was between -2 dB
and -7 dB in the worst eye (study eye). Subjects from multiple study
sites were randomized in a placebo-controlled trial of acetazolamide
with both treatment groups receiving a weight reduction program. We
used pointwise linear regression to classify each of the 52 visual field
test locations in the study eye as improving or not using the criterion
of a positive slope. In a separate analysis, differences in magnitude
in dB from baseline to final visit for the groups were computed and
ANOVA was used to determine the significance of differences at each
location.
Results: On average, subjects had 36 of 52 test locations with
improving visual thresholds over six months in the study eye. While
slopes of both groups improved, there were no significant differences
in slopes between the treatment groups. Thresholds improved across
the visual field with the magnitude of the change from baseline to
final visit in dB greatest and statistically significant around the blind
spot and the nasal area especially in the acetazolamide group. The
figure shows the difference in dB between the groups (effect size of
acetazolamide point by point).
Conclusions: While there were significant positive trends (slopes)
in visual thresholds over time for most participants there were no
significant differences between the groups. However, acetazolamide
treatment resulted in significant improvement in visual field function
with the magnitude of the changes greatest in the nasal and pericecal
areas; the latter is likely due to reduction in blind spot size related to
improvement in papilledema.
Point by point effect size in dB of acetazolamide found by subtracting
the average change from baseline of the placebo group from the
acetazolamide group.
Commercial Relationships: Michael Wall, None; Gideon Zamba,
None
Support: NORDIC 1U10EY017281-01A1
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Clinical Trial: NCT01003639
Program Number: 2235 Poster Board Number: B0088
Presentation Time: 3:45 PM–5:30 PM
Papilledema Outcome Evaluation in the OCT Substudy of the
Idiopathic Intracranial Hypertension Treatment Trial
Mark J. Kupersmith. 1Neuro-Ophthalmology, Roosevelt Hospital and
NYEE, New York, NY; 2Icahn School of Medicine at Mount Sinai,
New York City, NY.
Purpose: To demonstrate the effect of therapy on quantitative
imaging of papilledema in the Idiopathic Intracranial Hypertension
Treatment Trial (IIHTT). The IIHTT showed that acetazolamide
(ACZ) was efficacious in improving mild visual field loss in patients
with IIH. We showed that spectral domain optical coherence
tomography (SD-OCT) combined with custom 3-segmentation
analysis provides reliable continuous measurements of structural
changes in the optic nerve head and retina due to papilledema (OCT
Sub-Study Committee, IOVS in press).
Methods: Eighty-nine (43 ACZ, 46 placebo treated) IIHTT subjects
were evaluated at study entry and at 3 and 6 months with standard
automated perimetry, Frisén grading of photos, high and low contrast
visual acuity, and OCT imaging using the Cirrus SD-OCT. OCT
data were analyzed using custom 3-D segmentation algorithms to
calculate retinal nerve fiber layer (RNFL), total retinal thickness
(TRT), optic nerve volume (ONHV), and retinal ganglion cell layer
(GCL) measurements. Results for ‘study eyes’ (with worse perimetric
mean deviation, PMD, at baseline) were used for most analyses.
Results: At study entry, distributions of OCT measures were similar
in both treatment groups. At 6 months, ACZ group eyes showed
greater mean reductions in RNFL (175 mm vs. 89 mm, p=0.001),
TRT (220 mm vs. 113 mm, p=0.001), and ONHV (4.9 mm3 vs. 2.1
mm3, p=0.001) than placebo group eyes. For both treatment groups,
subjects with weight loss > 6% had greater mean reductions in RNFL
(156 mm vs. 103 mm, p=0.01), TRT (201 mm vs 127 mm, p=0.003),
and ONHV (4.3 mm3 vs. 2.6 mm3, p=0.002) than those with less
weight loss. GCL thinning was minor in the ACZ (3.6 mm) and
placebo (2.1 mm) groups. Interocular correlations were > 0.8 for all
3-D segmentation derived measurements. At 6 months, RNFL, TRT,
and ONHV correlated with Frisén grade (r=0.48-0.59, p<0.0001). At
6 months, the 21 eyes with GCL thickness <5th percentile of controls
had worse PMD (p=0.01) and both high (p=0.05) and low (p=0.01)
contrast acuity than for eyes with GCL > 5th percentile.
Conclusions: OCT measures of swelling due to papilledema in IIH
are effectively improved with ACZ and weight loss. In contrast to the
strong correlation at baseline (IOVS in press), 6 month RNFL, TRT,
and ONHV show only moderate correlations with papilledema grade.
Commercial Relationships: Mark J. Kupersmith, None
Support: U10 EY017281-01A1, U10 EY017387-01A1,
3U10EY017281-01A1S1
Clinical Trial: NCT01003639
Program Number: 2236 Poster Board Number: B0089
Presentation Time: 3:45 PM–5:30 PM
Ultramicroscopic study of the Optic Nerve Sheath in Patients
with Severe Vision Loss from Idiopathic Intracranial
Hypertension - Results
Marla Davis1, Joshua W. Evans1, Sachin Kedar2, Deepta Ghate3,
Peter Timoney1, Richard Kielar1, Bruce Maley5, William O’Connor4.
1
Ophthalmology, University of Kentucky, Lexington, KY;
2
Neurology, University of Nebraska, Omaha, NE; 3Ophthalmology,
University of Nebraska, Omaha, NE; 4Pathology, University of
Kentucky, Lexington, KY; 5Anatomy, University of Kentucky,
Lexington, KY.
Purpose: The objective of our study is to describe microscopic
changes in the optic nerve sheath (ONS) of patients with severe and/
or progressive vision loss from IIH.
Methods: ONS specimens were obtained at ONS fenestration in
IIH (cases) and enucleation for painful blind eye (controls). Both
procedures were performed by a single surgeon. After fixation
and staining, specimens were examined by masked experts using
light (LM), transmission electron (TEM) and polarization (PM)
microscopy for specimen quality and tissue anatomy (cellularity and
collagen structure).
Results: Of 12 specimens, 7 (6 cases, 1 control) met diagnostic
and quality criteria. For cases: Mean age was 31.25y; mean disease
duration 57 days; Mean CSF OP 40.25cm water. Papilledema grades
were II (3 eyes); III (1 eye); IV (2 eyes). 5/6 patients showed severe
visual field loss (MD> 15 dB); 3/6 had acuity worse than 20/40 and
2/6 had RAPD. All had normal CSF contents. Control ONS was
obtained from an enucleated eye of a 18y with childhood ocular
trauma.Collagen abnormalities on TEM: irregular arrangement
(all cases), collagen disruption and increased extracellular fluid
(5/6 cases) while control ONS showed regular, compact, normal
collagen. PM showed marked decrease in green yellow birefringence
(<20% in all cases with <5% in 4 cases) compared to control ONS
(75% birefringence) which confirmed abnormal collagen content
and arrangement in cases. All 6 cases showed increased cellularity
on LM and/or TEM with active fibroblasts (3/6 cases) and chronic
inflammatory cells (lymphocytes) in all 6 cases.
Conclusions: Disruption and disorganization of dural collagen in the
ONS from IIH points to significant shear forces on distal ONS from
raised ICP while increased cellularity indicates tissue repair. These
mechanical and inflammatory components could contribute to visual
loss in IIH. Early aggressive medical and/or surgical treatment may
be beneficial in IIH.
Commercial Relationships: Marla Davis, None; Joshua W. Evans,
None; Sachin Kedar, None; Deepta Ghate, None; Peter Timoney,
None; Richard Kielar, None; Bruce Maley, None; William
O’Connor, None
Support: Research to Prevent Blindness
Program Number: 2237 Poster Board Number: B0090
Presentation Time: 3:45 PM–5:30 PM
Ultramicroscopic study of the Optic Nerve Sheath in Patients
with Severe Vision Loss from Idiopathic Intracranial
Hypertension- Methodology
Joshua W. Evans1, Marla Davis1, Sachin Kedar2, Deepta
Ghate3, Peter Timoney1, Richard Kielar1, Bruce Maley4, William
O’Connor5. 1Ophthalmology, University of Kentucky, Lexington,
KY; 2Neurology, University of Nebraska Medical Center, Omaha,
NE; 3Ophthalmology, University of Nebraska Medical Center,
Omaha, NE; 4Anatomy and Neurobiology, University of Kentucky,
Lexington, KY; 5Pathology and Laboratory Medicine, University of
Kentucky, Lexington, KY.
Purpose: Very little is known about the anatomy and pathology of
the optic nerve sheath (ONS) in normal and diseased states. The
objective of our study is to explore microscopic changes in the ONS
in patients with severe and/or progressive vision loss from IIH.
Methods: ONS specimens were obtained from patients with IIH
after ONS fenestration (cases) and painful blind eye after enucleation
(controls). Both procedures were performed by a single surgeon.
A 2 x 1 mm ONS window was obtained, divided into 2 parts,
fixed and stained per following protocol.Light Microscopy (LM):
All specimens were formalin fixed, stained using HematoxylinEosin and examined at 10x and 40x magnification.Transmission
electron microscopy (TEM): All specimens were immediately
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
fixed (in Operating room) using 4% paraformaldehyde and 3.5%
glutaraldehyde on ice; washed in Cacodylate buffer; postfixed
using Osmium tetroxide/buffer mixture; dehydrated through graded
concentrations of ethanol washes; and resin embedded. Ultrathin
sections were obtained, stained and examined in Philips Tecnai
Biotwin 12 TEM at 2900X magnification.Polarization microscopy
(PM): All specimens were stained using Picrosirius red and examined
under polarization microscope using previously published methods.
(Junqueira et al., 1979) Masked experts in LM, TEM and PM
performed evaluations for specimen quality (desiccation, trauma and
staining) and tissue anatomy (cellularity and collagen arrangement).
Results: Of 13 subjects and 16 eyes enrolled, 7 specimens (6 cases
and 1 control) met inclusion and quality control criteria for analysis.
Tissue was not obtained in 4 eyes at surgery. 2 specimens were
excluded due to alternative diagnosis (meningioma, panophthalmitis).
3 specimens were excluded due to tissue desiccation resulting from
increased time interval from resection to tissue fixation.
Conclusions: Adequate quantity and quality ONS specimens were
obtained in patients undergoing ONS fenestration and enucleation.
Since ONS is susceptible to desiccation, tissue should be fixed
immediately in the operating room.
Commercial Relationships: Joshua W. Evans, None; Marla Davis,
None; Sachin Kedar, None; Deepta Ghate, None; Peter Timoney,
None; Richard Kielar, None; Bruce Maley, None; William
O’Connor, None
Support: Research to Prevent Blindness
Program Number: 2238 Poster Board Number: B0091
Presentation Time: 3:45 PM–5:30 PM
Multicolor imaging in the assessment and diagnosis of optic disc
swelling
Andy Malem, Stephanie West, Gabriella De Salvo. Southampton
General Hospital, Southampton, United Kingdom.
Purpose: To examine the use of the recently developed Multicolor
imaging (Heidelberg Spectralis) as an adjunct to traditional imaging
modalities in the assessment of patients with suspected optic disc
swelling, and to determine whether Multicolour (MC) can help
in the differential diagnosis between true optic disc swelling and
pseusopapilloedema.
Methods: Prospective consecutive study of 19 patients who
presented to our clinic with suspected bilateral optic disc swelling.
MC was performed on all patients in addition to fundoscopy, retinal
nerve fiber layer optical coherence tomography (OCT) and fundus
autofluorescence (FAF). MC combines three different wavelengths
to enhance different retinal layers: 488nm (blue), 536nm (green) and
786nm near infrared (NIR). All images were analyzed by a medical
retinal specialist.
Results: Of the 19 cases, 12 (63%) were female and 7 (37%) were
male, with an average age of 19. Diagnosis of true papilloedema
versus pseudopapilloedema was confirmed in all patients with a
multidisciplinary approach. In fact 17 (89%) patients had raised
intracranial pressure (ICP) confirmed by lumbar puncture opening
pressure or brain imaging, and 2 (11%) had optic disc drusen. In
those with true optic disc swelling secondary to raised ICP, MC
illustrated a green shift correlating to the thickened retinal nerve fiber
layer (RNFL) seen both clinically and on the optic disc OCT. The
disc margins were indistinguishable at the green reflectance and a
double ‘shadow’ was seen on the NIR reflectance. Unlike those with
raised ICP, the patients with optic disc drusen did not present a green
shift on the MC image and the disc margins were well delineated by
a ring of hyperreflectance seen at the green reflectance; no thickening
of the RNFL was detected.
Conclusions: Our results show that MC is a useful additional
imaging modality in the diagnosis of true swollen optic discs and
can provide additional information to help determine the underlying
diagnosis in true and pseudopapilloedema.
Commercial Relationships: Andy Malem, None; Stephanie West,
None; Gabriella De Salvo, None
Program Number: 2239 Poster Board Number: B0092
Presentation Time: 3:45 PM–5:30 PM
Papilledema Associated with Infantile Hypophosphatasia and
Craniosynostosis
Constance E. West2, 1, Robert B. Hufnagel3, 4, Howard M. Saal3, 4.
1
Department of Ophthalmology, University of Cincinnati, Cincinnati,
OH; 2Division of Pediatric Ophthalmology, Cincinnati Children’s
Hospital Medical Center, Cincinnati, OH; 3Division of Human
Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati,
OH; 4Department of Pediatrics, University of Cincinnati, Cincinnati,
OH.
Purpose: Hypophosphatasia (HPP) is a rare disease caused by
reduced activity of alkaline phosphatase (ALP), and is secondary
to mutations in ALPL, the gene encoding tissue-nonspecific ALP
(TNSALP). There are at least six clinical forms and the spectrum
of disease is wide, ranging from stillbirth to pathologic fractures
in adulthood. Craniosynostosis and papilledema may accompany
the infantile and childhood forms. There are six reported cases of
craniosynostosis and papilledema in HPP; however, none contain
ophthalmic follow-up. We report our experience with three patients
with infantile HPP, craniosynostosis, and papilledema.
Methods: Patients received comprehensive ophthalmic examination
and follow-up while receiving treatment for complications of
infantile HPP.
Results: A 5.5 month old girl was diagnosed with HPP (compound
heterozygote: c.1327G>T, p.Ala443Ser; c.1471G>A, p.Gly491Arg),
and with craniosynostosis at six months of age. On ophthalmic
examination, 3+ papilledema was found. Two and a half months
after cranial vault expansion, papilledema worsened, and a second
cranial vault expansion was performed. Four months after the second
procedure, the papilledema had resolved and the nerves were pink
and healthy with normal visual behavior for age. There has been
no recurrence 7 months postoperatively. A 27 month old male was
referred for management of complications of HPP (homozygous
c.293C>T, p.S98F). Craniosynostosis was found on clinical and
radiologic examination and ophthalmologic consultation showed
2+ disc swelling bilaterally; cranial vault expansion was performed.
Disc swelling resolved after 4.5 months, and 14 months after cranial
vault expansion, the nerves remain pink and healthy with normal
visual behavior. His sister (same mutation) was referred at 5.5 years.
Infantile HPP was diagnosed at 8 months and nystagmus was noted
at 3.5 years. On examination, she had craniosynostosis, bilateral
optic atrophy, roving nystagmus, and left exotropia. A cranial vault
expansion was performed. At 6.5 years old, acuity was 20/250 OD
and hand motions OS, a red green color vision defect, and constricted
fields. The nerves remain atrophic.
Conclusions: Untreated papilledema resulted in visual impairment,
but prompt treatment of elevated intracranial pressure associated
with craniosynostosis in HPP leads to resolution of papilledema over
several months’ time.
Commercial Relationships: Constance E. West, None; Robert B.
Hufnagel, None; Howard M. Saal, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
308 Optic nerve
Tuesday, May 05, 2015 8:30 AM–10:15 AM
4CD Mile High Blrm Paper Session
Program #/Board # Range: 2603–2609
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Program Number: 2603
Presentation Time: 8:30 AM–8:45 AM
TSH/M22 induces TNFα production in human fibrocytes:
mechanistic aspects
Shannon J. Shan, Tong Wu, Tunde Mester, Raymond Douglas.
Ophthalmology, University of Michigan, Ann Arbor, MI.
Purpose: Fibrocytes (FC) are bone marrow-derived progenitor
cells implicated in various conditions of inflammation and fibrosis.
In Graves disease (GD) and Graves orbitopathy (GO), circulating
FCs become more abundant and can infiltrate the thyroid and
orbit. FCs express high levels of thyrotropin receptor (TSHR) and
insulin growth factor-1 receptor (IGF-1R), two putative pathogenic
autoantigens in GO. The role of the FCs and these receptors in the
pathogenesis of GO remains to be fully delineated. Treatment of
FCs with thyroid stimulating hormone (TSH) or M22 (activating
TSHR antibody) induces the production of a multitude of cytokines,
including the key pro-inflammatory cytokine, tumor necrosis factor α
(TNFα). This study aims to characterize the molecular mechanisms
underlying TSH/M22-induced TNFα production in FCs.
Methods: Circulating and cultured FCs from healthy and GD
patients were treated with various combinations of TSH, M22,
MG132 and AKTi (inhibitors of NF-kB and Akt, respectively),
and teprotumumab (TMB, a human monoclonal IGF-1R blocking
antibody). Extracellular and intracellular TNFα protein production
was measured by Luminex and flow cytometry, respectively.
Messenger RNA expression was quantified by real time PCR.
Results: Treatment with TSH or M22 induced significant TNFα
protein and mRNA production by FCs. TSH-induced TNFα
protein production in cultured FCs was reduced by 53% and 81%
when pretreated with MG132 and AKTi, respectively (p<0.0001).
Similarly, TSH-induced TNFα mRNA expression was reduced from
93-fold to 16-fold expression with MG132 (p<0.001), and from 23fold to 1.3-fold expression with AKTi (p<0.0001). TMB decreased
TSH-induced TNFα protein production in circulating FCs from mean
fluorescent index (MFI) value of 2.92 to 1.91, and mRNA expression
in cultured FCs from 141- to 52-fold expression (p<0.0001). TMB
also decreased M22-induced TNFα protein production from MFI
of 1.67 to 1.12, and mRNA expression from 6- to 3-fold expression
(p<0.0001).
Conclusions: TSH/M22 stimulates FCs to produce TNFα. Both
steady state mRNA and protein levels are increased. This process
involves the transcription factor NF-kB and its regulator Akt. TMB
attenuates this activating effect of TSH/M22, suggesting that TSHR
downstream signaling may be partially dependent on IGF-1R
signaling. By modulating the proinflammatory properties of FC such
as TNFα production, TMB may be a promising therapeutic agent for
GO.
Commercial Relationships: Shannon J. Shan, None; Tong Wu,
None; Tunde Mester, None; Raymond Douglas, None
Support: EY008976, EY011708, DK063121, EY016339, EY021197,
EY007003 Eye Core Grant, an unrestricted grant from Research
to Prevent Blindness, a Research to Prevent Blindness Career
Development Award, Research to Prevent Blindness Lew Wasserman
Merit Award, and the Bell Charitable Foundation
Program Number: 2604
Presentation Time: 8:45 AM–9:00 AM
Mitochondrial DNA instability and dysregulated mitochondrial
quality control contribute to progressive retinal ganglion cell loss
in dominant optic atrophy
Patrick Yu-Wai-Man1, 2, Chunyan Liao3, 4, Neil Ashley3, 4, Padraig J.
Flannery1, Massimo Zeviani6, Anna K. Simon5, Patrick F. Chinnery1,
Joanna Poulton3, 4. 1Institute of Genetic Medicine, Newcastle
University, Newcastle Upon Tyne, United Kingdom; 2UCL Institute
of Ophthalmology, Moorfields Eye Hospital, London, United
Kingdom; 3Nuffield Department of Obstetrics and Gynaecology, The
Women’s Centre, University of Oxford, Oxford, United Kingdom;
4
Oxford Medical Genetics Laboratories, Churchill Hospital, Oxford,
United Kingdom; 5NIHR Translational Immunology Laboratory,
Nuffield Department of Medicine, University of Oxford, Oxford,
United Kingdom; 6MRC Mitochondrial Biology Unit, University of
Cambridge, Cambridge, United Kingdom.
Purpose: Autosomal dominant optic atrophy (DOA) is a
mitochondrial optic neuropathy caused by pathogenic mutations
within the OPA1 gene (3q28-q29), which encodes for an inner
mitochondrial membrane protein. The neuronal loss observed in
DOA represents an attractive monogenic disease model to dissect
the overlapping pathological pathways in more complex adult-onset
neurodegenerative disorders. However, the fundamental mechanisms
by which OPA1 mutations ultimately precipitate retinal ganglion cell
(RGC) loss have still not been clarified.
Methods: We made use of a comprehensive OPA1 tissue biobank
comprised of muscle biopsy specimens (n=30) and primary fibroblast
cell lines (n=40) established from patients with both isolated optic
atrophy and the more severe syndromic “DOA plus” phenotypes.
By using a series of validated experimental assays, the following
cellular parameters were assessed: (i) mitochondrial respiratory chain
integrity; (ii) mitochondrial DNA (mtDNA) instability with real-time
PCR and ultra-deep next generation sequencing; (iii) the kinetics
of mitochondrial genome replication following a period of mtDNA
depletion induced with ethidium bromide; and (iv) mitochondrial
quality control (mitophagy) using a high-throughput flow cytometry
protocol that allows rapid co-localisation of autophagosomes and
quantification of LC3-positive puncta.
Results: OPA1 mutations result in a significant mitochondrial
biochemical defect in both skeletal muscle and fibroblasts, and a
clear correlation was observed with clinical disease severity. An
accumulation of secondary mtDNA abnormalities was also observed,
implicating marked mitochondrial genome instability secondary to an
imbalance between mitochondrial fusion and fission. This impairment
in the cell’s mtDNA replication machinery was further exacerbated
following a period of mtDNA depletion induced with ethidium
bromide treatment. Importantly, there was a dramatic reduction in
the cell’s ability to handle exogenous pro-apoptotic stress due to the
inappropriate activation of mitophagic pathways in a compensatory
effort to eliminate dysfunctional mitochondria.
Conclusions: MtDNA instability and impaired mitochondrial quality
control are important synergistic mechanisms that contribute to
neuronal loss in DOA, and they represent attractive disease pathways
amenable to therapeutic intervention.
Commercial Relationships: Patrick Yu-Wai-Man, None;
Chunyan Liao, None; Neil Ashley, None; Padraig J. Flannery,
None; Massimo Zeviani, None; Anna K. Simon, None; Patrick F.
Chinnery, None; Joanna Poulton, None
Support: Medical Research Council (MRC, UK) Clinician Scientist
Fellowship (G1002570)
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 2605
Presentation Time: 9:00 AM–9:15 AM
Cecocentral Scotoma: A Neuro-Ophthalmic Revisionist Approach
Steven A. Newman. Ophthalmology, University of Virginia,
Charlottesville, VA.
Purpose: Although homonymous hemianopsia, bitemporal, and
arcuate visual field defects are by far the most common, the most
classic visual field defect in neuro-ophthalmology has been the
central scotoma. Literature from the mid-20th century emphasized
the unique nature of cecocentral scotomas seen in patients with
toxic and nutritional pathology. The fact that macular pathology can
produce central scotomas has also been recognized and the distinction
between retinal and neuro-ophthalmic disease has proved to be a
major clinical distinction.
Methods: A retrospective study of 193 patients referred to the NeuroOphthalmology Division at the University of Virginia and coded for
central and cecocentral scotomas. Patterns were analyzed. Foveal
sensitivity was available on all fields. Most patients were studied
with a 10-2 program as well as a 24-2 program. Some patients were
studied with a V size test object (dense defects or poor central vision).
Results: Twenty-nine charts were excluded for either transient
central scotomas, or what appeared to be arcuate or paracentral
defects. Fourteen charts were classified as unknown etiology. Of
the remaining 150 patients, 80 had evidence of macular pathology,
(67 having clear maculopathy and 13 with retinal vascular disease).
Of those with primary optic nerve pathology, optic neuritis and
compressive optic neuropathies (24 each) were the most common.
This was followed by anterior ischemic optic neuropathy (17 cases),
2 patients with neuroretinitis, 2 patients with neuromyelitis optica,
and 1 patient with traumatic optic neuropathy. The classical finding of
central scotomas was seen in 2 cases of Leber’s, 1 case of dominant
optic atrophy, 2 cases of nutritional optic neuropathy, and 1 case of
toxic optic neuropathy.
Conclusions: In spite of a selective referral bias, retinal disease was
the most common pathophysiology causing central and cecocentral
scotomas. The addition of OCT and anatomic studies helped to
distinguish these, although even when the macula looked normal,
functional studies such as multifocal ERG may be necessary. The
use of the 10-2 program and a V size test object is often necessary to
recognize the pattern of field defect. Even classical, toxic, metabolic,
and hereditary optic neuropathies may involve central fixation
without extension to the blind spot.
Commercial Relationships: Steven A. Newman, None
Program Number: 2606
Presentation Time: 9:15 AM–9:30 AM
Leber’s Hereditary Optic Neuropathy (LHON) Open Label
Clinical Study for EPI-743: 2015 update
Rustum Karanjia4, 1, Edward R. Chu1, Shellee Rockwell4, Matthew
Klein2, Guy Miller2, Fillipe Chicani3, Fred N. Ross-Cisneros1, Alfredo
A. Sadun4, 1. 1Doheny Eye Institute, Los Angeles, CA; 2Edison
Pharmaceuticals, Mountain View, CA; 3Ophthalmology, Universidade
Federal de São Paulo,, São Paulo,, Brazil; 4Ophthalmology,
University of California at Los Angeles, Los Angeles, CA.
Purpose: LHON is a maternally inherited disease characterized by
sudden and profound loss of central vision in both eyes. The purpose
of this study is to describe the 4 year results of treating LHON with
a novel experimental quinone, EPI-743, in 7 consecutively enrolled
patients all with the 11778 LHON mutation.
Methods: Seven of 11 affected LHON patients treated with EPI-743
as part of this clinical study have been on continuous therapy for 4
years. Outcome measurements of efficacy include visual acuity (VA)
(improvement if 2 or more lines of change or off to on chart), visual
fields (VF) (improvement if >5dB of changes in mean deviation),
OCT, and color vision (improvement if ≥ 2 plates in Ishihara plates,
or from 0 to 2 plate). Thirteen eyes of 7 patients were included (one
patient had retinal detachment in one eye) and two time points were
compared, 6 months post onset and their most recent visit between
36-48 months into therapy. After six months, the natural history for
affected patient with the 11778 LHON mutation is for vision to either
stabilize or slowly deteriorate. This information is presented and
discussed in a separate abstract submission.
Results: VA: Nine of 13 eyes improved (70%), one to 20/20 level
(from 20/300) and 8 from off chart to on chart. 4 eyes (30%) of 2
patients remained off chart. VF: 4 (30%) eyes improved, 8 (62%)
were unchanged and 1 (8%) was worse than the 6 month VF. Color:
3 eyes (24%) improved (one 3/14 to 7/14, rest 0/14 to 2/14), 5 eyes
(38%) were able to see only 1 color plate, and 5 eyes (38%) remained
unable to see any color plates. OCT: All patients presented with
progressive loss of fibers over time (25 to 50% of the normal values).
These improvements were favorable in comparison to the natural
history of 11778 LHON.
Conclusions: EPI-743 treatment improved vision by these criteria
in 56% of treated eyes. Visual improvement was noted up to 4
years following initiation of therapy suggesting that there is a
large therapeutic window for recovery with EPI-743. There were
no significant drug-related adverse events or clinical laboratory
abnormalities. EPI-743 is a safe and effective treatment for LHON
for most patients. This data is part of an ongoing compassionate use
study.
Commercial Relationships: Rustum Karanjia, None; Edward
R. Chu, Edison Pharmaceuticals (C), Edison Pharmaceuticals (F);
Shellee Rockwell, None; Matthew Klein, Edison Pharmaceuticals
(E); Guy Miller, Edison Pharmaceuticals (E); Fillipe Chicani,
Edison Pharmaceuticals (C); Fred N. Ross-Cisneros, Edison
Pharmaceuticals (F); Alfredo A. Sadun, Edison Pharmaceuticals (F)
Clinical Trial: NCT02300753
Program Number: 2607
Presentation Time: 9:30 AM–9:45 AM
Macular Retinal Sublayer Thickness Changes in Patients and
Carriers in the Natural History Phase of the Leber Hereditary
Optic Neuropathy G11778A Gene Therapy Clinical Trial
Byron L. Lam, Samuel P. Burke, Mindy X. Wang, Gloria A. Nadayil,
Giovanni Gregori, William J. Feuer, Potyra R. Rosa, Sophia
Cuprill-Nilson, Ruth Vandenbroucke, John Guy. Bascom Palmer Eye
Institute, University of Miami, Miami, FL.
Purpose: We determined macular retinal sublayer thickness changes
of patients and carriers with G11778A Leber hereditary optic
neuropathy (LHON) by utilizing data from the natural history phase
of the gene therapy trial where subjects underwent visual examination
every 6 months from 2008 to 2013.
Methods: Spectral-domain Cirrus OCT 512x128 macular cube
scans were segmented for the baseline examination. Segmented
retinal sublayers were the RNFL, GCL-IPL, INL-OPL, ONL-IS,
and OS. Poor quality scans that cannot be segmented accurately
were excluded. The thickness of the retinal sublayers of the LHON
affected subjects and asymptomatic carriers were compared to a
normal group.
Results: Segmented macular OCT data were available from
20 LHON affected subjects (age 31+14 years, range 10-61), 31
asymptomatic LHON carriers (age 38+18, 9-65), and 14 normal
subjects (age 39+13, 23-61). In general, parameters were not
significantly correlated with age in any of the groups. There were no
differences between carriers and normals for any sublayers but some
layers were thinner or thicker in LHON subjects. Layers showing
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
the most striking differences between LHON and the other two
groups included the RNFL, GCL-IPL, and OS (p-values from 0.046
to <0.001). LHON RNFL and GCL-IPL were thinner than carriers
and normals while LHON OS was thicker than carriers and normals.
Differences between groups were not significant in the INL+OPL.
The ONL+IS layer of the temporal and inferior quadrants (inner and
outer macular annular rings) was thicker in LHON (0.041≥p≥0.009).
Conclusions: LHON affected patients, compared to normal
subjects, have thickened photoreceptor outer segment layer and
some thickening of the ONL-IS in spite of having thinner RNFL and
GCL-IPL layers. Asymptomatic LHON carriers have retinal sublayer
thickness similar to normal subjects. The findings indicate optic nerve
degeneration in LHON also has an effect on the morphology of the
outer retinal layers of the macula.
Commercial Relationships: Byron L. Lam, None; Samuel P.
Burke, None; Mindy X. Wang, None; Gloria A. Nadayil, None;
Giovanni Gregori, None; William J. Feuer, None; Potyra R. Rosa,
None; Sophia Cuprill-Nilson, None; Ruth Vandenbroucke, None;
John Guy, None
Support: 1U10EY023558-01A1
Program Number: 2608
Presentation Time: 9:45 AM–10:00 AM
Leber Hereditary Optic Neuropathy Gene Therapy (LHON)
Clinical Trial: Initial Results
John Guy1, William J. Feuer1, Vittorio Porciatti1, William W.
Hauswirth2, Janet L. Davis1, Byron L. Lam1, Rajeshwari D.
Koilkonda1, Huijun Yuan1, Phillip Gonzalez1, Anil Lalwani1. 1Bascom
Palmer Eye Institute, Miami, FL; 2Ophthalmology, University of
Florida, Gainesville, FL.
Purpose: To determine the safety and tolerability of
AAV2(Y444,500,703F)-P1ND4v2 (a nuclear encoded version wildtype ND4 imported into the mitochondria with the addition of a
targeting sequence) in patients with LHON.
Methods: After obtaining informed consent for participation in
this open-label, unilateral single-dose, intravitreal injection of
AAV2(Y444,500,703F)-P1ND4v2 per subject in a dose-escalation
study designed to investigate the safety of three vector doses
(5x109 vg, 2.46x1010 vg and 1x1011 vg) in subjects with molecularly
confirmed G11778A-mutated mitochondrial DNA; two patients with
long-standing (>12 months) and bilateral acuity loss down to ≤ 35
ETDRS letters (20/200) received intravitreal injections of low dose
study drug (5x109 vg) into the eye with worse acuity. Clinical testing
included ETDRS visual acuity, Humphrey visual fields (30-2), OCT,
pattern ERG (PERG) and neuro-ophthalmic examinations. Blood
samples were screened for neutralizing antibodies (Nabs) to AAV2
prior and after intravitreal injection. Postinjection evaluations thus far
are 1 month in the first patient and one week in the second patient.
Results: Visual acuity of patient 1 was hand movements prior to
injection and remained at that level one day, one week and 1-2
months after injection. No haze, cells or inflammation was detected
in the vitreous or anterior chamber and retinal examination remained
normal showing only optic atrophy . RNFL was 54 mm prior to
injection and 56 mm after injection. HVF MD remained -32.8. PERG
amplitudes were 0.17 mV, within noise levels, prior to injection and
0.27 mV after injection . Visual acuity of patient 2 was counting
fingers prior to and one week after injection. PERG amplitudes were
0.45 -0.48 mV prior to injection and 0.57 mV 1 week postinjection.
Both patients had NAb titers of 1:20,480 prior to injection that did
not change after injection. Vector genomes were not detected in the
blood.
Conclusions: Thus far study drug appears to be safe and welltolerated. After the 3rd patient is injected we will evaluate the higher
doses in this chronic cohort then evaluate safety in subjects with a)
acute (<12 months) bilateral loss of visual acuity to < 35 ETDRS
letters and b) with acute (<12 months) unilateral loss of acuity to <35
ETDRS letters, but who have “good acuity” ≥ 70 letters (20/40) in the
contralateral eye with better acuity selected for injection.
Commercial Relationships: John Guy, None; William J. Feuer,
None; Vittorio Porciatti, None; William W. Hauswirth, AGTC
(F); Janet L. Davis, None; Byron L. Lam, None; Rajeshwari D.
Koilkonda, None; Huijun Yuan, None; Phillip Gonzalez, None;
Anil Lalwani, None
Support: 1U10EY023558-01A1
Clinical Trial: NCT02161380
Program Number: 2609
Presentation Time: 10:00 AM–10:15 AM
Chronic Optic Neuropathy Causes Decreases in both Inner
Retinal Blood Flow and Prelaminar Optic Nerve Blood Flow
Randy H. Kardon1, 2, Enrique Rivera1, Susan C. Anderson2, 1, Jan
M. Full2, 1, Michael Wall1, 2, Robert Mallery1, Matthew Thurtell1, 2.
1
Ophthalmology and Visual Sciences, University of Iowa, Iowa City,
IA; 2Research, Veterans Affairs Medical Center, Iowa City, IA.
Purpose: Our purpose was to determine in a prospective,
observational clinical study if optic neuropathy results in an
obligatory decrease in blood flow to the inner retina and optic nerve
due to decreased metabolic demand from non-functioning neurons.
Visual stimulation causes transient hyperemia, but it is unknown if
decreases in neuron activity cause reduced blood flow.
Methods: Laser speckle blood flowgraphy imaging (LSFG-NAVI;
Softcare Ltd, Fukuoka, Japan) was performed on a 25x20 degree
area of the fundus incorporating the optic nerve head. Blurring of the
laser speckle pattern by moving particles in the image plane was used
to simultaneously measure blood flow in the major circumpapillary
retinal arteries and veins, and below the surface of the optic nerve
head. Blood flow was determined in each eye of 19 patients
with unilateral optic neuropathy (ischemic=13, compressive=5,
inflammatory=1) in the chronic state. Inner retinal blood flow
and optic nerve head blood flow were compared between affected
and unaffected eyes. Retinal nerve fiber layer (RNFL) and retinal
ganglion cell layer complex (GCL) were compared to retinal and
optic nerve blood flow.
Results: There was a significant decrease in inner retinal blood
flow (supplied by branches of the central retinal artery) in eyes with
optic neuropathy compared to the fellow normal eye (P=0.002;
mean=69±17% of fellow eye). A significant decrease in optic nerve
head blood flow deep to the superficial retinal capillaries overlying
the optic nerve was also present (P<0.001; mean=65±22% of fellow
eye). There was also significant decrease in both RNFL (P=0.02;
mean=83±32% of fellow eye) and GCL thickness (P<0.001;
mean=71±11% of fellow eye), but no significant correlation between
the inter-ocular asymmetry of retinal or optic nerve blood flow and
RNFL or GCL thickness.
Conclusions: Chronic optic neuropathy results in decreased retinal
and optic nerve head blood flow, likely due to reduced metabolic
demand. Laser speckle blood flowgraphy allows non-invasive
simultaneous measurement of retinal, choroidal, and optic nerve
head blood flow, which may be proportional to metabolism and
neurovascular coupling.
Commercial Relationships: Randy H. Kardon, Department of
Veterans Affairs Research Foundation (S), Fight for Sight (S),
Novartis (F); Enrique Rivera, None; Susan C. Anderson, None;
Jan M. Full, None; Michael Wall, None; Robert Mallery, None;
Matthew Thurtell, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Support: NEI R009040554; R01 EY018853, VA Rehabilitation
Research and Development; C9251-C; 1I01RX000889-01A1,
Department of Defense; TATRC; W81XWH-10-1-0736;
W18XWH-10-1-0561, Novartis steering committee OCTiMS
318 Eye movements / Nystagmus / Central field loss
Tuesday, May 05, 2015 8:30 AM–10:15 AM
Exhibit Hall Poster Session
Program #/Board # Range: 2902–2929/D0001–D0028
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Contributing Section(s): Visual Psychophysics/Physiological
Optics, Visual Neuroscience
Program Number: 2902 Poster Board Number: D0001
Presentation Time: 8:30 AM–10:15 AM
Eye-hand reference frames misalign after central field loss
Terence L. Tyson1, Laura Walker1, 2, Anna Ma-Wyatt3, Donald C.
Fletcher4, 1. 1The Smith-Kettlewell Eye Research Institute, Daly City,
CA; 2Envision Inc., Wichita, KS; 3University of Adelaide, Adelaide,
SA, Australia; 4Frank Stein and Paul S. May Center for Low Vision
Rehabilitation, San Francisco, CA.
Purpose: When central vision is lost and a preferred retinal locus
(PRL) develops in the periphery, typical eye-hand coordination
may be disrupted. In cases of AMD, reach initiation is delayed
(Timberlake et al., 2011) and saccades can be misdirected (Renninger
et al., 2012). This work examines the degree to which the reach
trajectory is affected by central field loss (CFL).
Methods: Subjects with CFL and age-matched controls performed
a rapid reach to a high contrast dot on a touch sensitive screen. The
dot can occur in 1 of 8 locations surrounding fixation at varying
distances. Subjects received negative feedback if reach time or
touch endpoint error criteria was violated. Reach time limits were
determined for each subject during practice trials, and defined as
the critical reach duration in which accuracy began to decline.
Eye and hand movement trajectories were tracked (SR Eyelink
1000 and Polhemus Liberty Motion Tracker) and touch endpoints
were collected (ELO Touchscreen). Viewing was binocular, with
tracking of the dominant/better eye. Monocular scotoma and PRL
locations were measured with microperimetry. The foveal pit was
localized relative to the scotoma and PRL utilizing optical coherence
tomography (OCT/SLO by Optos). Reach trajectories were analyzed
for initiation time, peak velocity, total duration, tortuosity and
directional bias. Accuracy and precision of endpoint errors were also
analyzed.
Results: Reach initiation was delayed relative to age-matched healthy
controls, yet overall trajectories were smooth and exhibited ageappropriate dynamics. Eye movements tended to bring the fixational
PRL close to the target before onset of reach initiation. Directionality
of the reach toward the target exhibited more variability in CFL
subjects, yet endpoint precision was not worse than predicted given
PRL eccentricity (i.e., visual acuity). In several cases, PRL landing
was notably biased off of the target in a direction that pulled the
non-functioning fovea closer to the target, suggesting incomplete rereferencing of eye-hand coordination to the PRL.
Conclusions: In many cases of CFL, fixation is re-referenced to the
PRL. This “remapping” does not always extend completely to the
hand, resulting in an offset between PRL and reach endpoints. The
misalignment between the eye and hand may pose a problem for
dexterity, especially when moving under time pressure. Rehabilitation
that targets eye-hand realignment may provide a benefit.
Commercial Relationships: Terence L. Tyson, None; Laura
Walker, None; Anna Ma-Wyatt, None; Donald C. Fletcher, None
Support: NEI R01 Grant EY022156
Program Number: 2903 Poster Board Number: D0002
Presentation Time: 8:30 AM–10:15 AM
Characteristics of Monocular Smooth Pursuit in Central Field
Loss
Natela M. Shanidze, Elena Potapchuk, Giovanni Fusco, Stephen
Heinen, Preeti Verghese. Smith-Kettlewell Eye Research Institute,
San Francisco, CA.
Purpose: Currently, it is not well known how people with central
field loss (CFL) pursue moving targets, a behavior that has been
attributed to the fovea (Krauzlis 2003). Optimizing pursuit behavior
may be especially important for this population, as it can afford
additional time to visualize a moving object of interest. As the
position of the target changes during the task, it is important to assess
pursuit characteristics in the context of the target’s location relative to
a subject’s scotoma and preferred retinal loci (PRL). Here, we present
results describing monocular smooth pursuit in CFL patients using a
novel approach employing a scanning laser ophthalmoscope (SLO)
that allows for a direct visualization of the target on the damaged
retina.
Methods: Six (5 AMD, 1 JMD) individuals with differing degrees
of CFL were recruited. Monocular scotomas were assessed using
standard microperimetry in an SLO. Subsequent to mapping
each scotoma, observers pursued in a step ramp (Rashbass 1961)
paradigm. They first fixated a central target (1°) for 1 second.
The target then disappeared, and reappeared 6° away, moving at
a constant speed (~5°/s), in one of 8 possible directions (in 45°
increments), selected at random. Participants were asked to follow
the target with their eyes.
Results: CFL patients demonstrated reasonable pursuit of moving
targets, with pursuit velocity gain (0.16-1.79) dependent on whether
the target moved into or out of the scotoma. Gains were lowest for
targets moving toward the scotoma and highest for those moving out
of and away from it. Pursuit latencies mirrored gains. Fig 1 shows
pursuit of a target moving out of the scotoma for one observer.
A computed gain modulation index (MI) that characterized the
difference between maximum and minimum gains across target
trajectories correlated with scotoma size (Fig 2).
Conclusions: Despite absence of the fovea, CFL patients could
smoothly pursue moving targets during the majority of trials. Pursuit
gains were highest for targets moving out of the scotoma, suggesting
subjects were trying to catch up with the target. For targets starting
opposite the scotoma and moving towards it, our results are contrary
to the expectation that patients would pursue the target to avoid
having it disappear into the scotoma. One potential explanation is that
individuals have some knowledge of the scotoma and are unwilling to
pursue a target if it means obscuring the center of the visual field.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Commercial Relationships: Natela M. Shanidze, None; Elena
Potapchuk, None; Giovanni Fusco, None; Stephen Heinen, None;
Preeti Verghese, None
Support: R01 EY022394, NIH; Rachel C. Atkinson & C.V. Starr
Postdoctoral Fellowship, Smith-Kettlewell Eye Research Institute
Program Number: 2904 Poster Board Number: D0003
Presentation Time: 8:30 AM–10:15 AM
Compensatory strategies for independent binocular scotomas in
simulated CFL
Concetta F. Alberti1, Peter J. Bex2. 1Schepens Eye Research Institute,
Boston, MA; 2Department of Psychology, Northeastern University,
Boston, MA.
Purpose: People with central field loss (CFL) can learn to use a
Preferred Retinal Locus (PRL) in peripheral vision as a substitute
fovea. The location of the PRL is generally measured monocularly,
however people with CFL typically have asymmetric monocular
scotomata forming a compound binocular scotoma. We simulate
CFL with independent monocular scotomata in each eye of
normally sighted observers to examine binocular visual function and
oculomotor control with asymmetric vision loss.
Methods: Gaze contingent binocular scotomata were simulated in 11
normally sighted participants using an Eyelink 1000Hz eye tracker
and 3D stereoscopic shutter glasses. A Gaussian (σ=1°, 2°, 4° or 8°
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
in different sessions) windowed patch of 100% contrast pink noise
was positioned at the point of gaze of each eye on a 144Hz computer
display (Lmean=25 cd/m2). In each session, observers were instructed
to freely-view the screen and to identify a sequence of 50 black (0.1
cd/m2) SLOAN letters presented at the screen centre. Each letter was
presented until the observer responded and its size was under control
of an adaptive staircase. Binocular eye positions were recorded
throughout each session so that retinal position of the target, fixation
stability and vergence could be determined.
Results: As the scotoma size increased, fixation shifted to a greater
eccentricity (p<0.05) and fixation instability increased (p<0.05), in
line with previous studies of monocular PRL behaviour, however
visual acuity did not significantly worsen with scotoma size (p=0.07).
In addition, spontaneous binocular fixation patterns differed for
different scotoma sizes: for the 2 smaller scotomata, observers made
vergence eye movements that brought the target onto a ‘disjunctive
PRL’ (p<0.05); for the 2 larger scotomata, observers made conjugate
eye movements that brought the target onto a ‘conjunctive PRL’.
Conclusions: Simulation of independent binocular CFL reveals
strategic oculomotor behaviour that cannot be predicted from studies
of real or simulated monocular CFL.
Observers spontaneously adopt a PRL that under some conditions is
in a correlated location in each eye – conjunctive PRL. However, for
small scotomata the PRL may be in uncorrelated locations in each
eye – disjunctive PRL – which suggests that they may use binocular
vergence eye movements to bring a target into a sighted area of their
3D visual field.
Commercial Relationships: Concetta F. Alberti, None; Peter J.
Bex, None
Program Number: 2905 Poster Board Number: D0004
Presentation Time: 8:30 AM–10:15 AM
Adaptation to optically induced simultaneous bifocal vision
Aiswaryah Radhakrishnan, Carlos Dorronsoro, Susana Marcos.
Instituto de Optica, CSIC, Madrid, Spain.
Purpose: To evaluate in subjects neural adaptation to optically
induced simultaneous vision corrections in presence of their natural
aberrations.
Methods: A modified Simultaneous Vision simulator was used to
produce pure bifocal images. The shift in Perceived Best Focus (PBF,
i.e. amount of blur that is perceived as neutral) following adaptation
to bifocal images was measured in four normal subjects. Adapting
images were real bifocal images of different additions (achieved
by combining two Badal channels focused for distance and near:
0.5D, 1.5D, and 3D) and proportions of near/far energy (produced
by a spatial light modulator: 100%Blur (B)/0%Sharp (S), 75B/25S,
50B/50S, 25B/75S, 0B/100S). A total of 9 bifocal blur patterns, 3
pure defocus, 1 sharp, and 1 gray adaptation conditions were tested.
Test images were 301 pure defocus images, simulated by convolution
with 0 to 3D spherical blur of a face (subtending 2 deg at retina). The
PBF was obtained with a blur detection task in a QUEST paradigm
(subject responded for each test image whether it was sharp or
blurred). The PBF shift was calculated as the difference between
the PBF following every adapting image and the PBF following
gray adaptation. All measurements were performed under paralyzed
accommodation and a 5-mm pupil diameter artificial pupil.
Results: The average PBF across subjects was 0.63±0.17D following
gray adaptation and 0.51±0.1D following sharp adaptation (natural
viewing), with no statistically significant differences (p=0.08)
between these conditions. A high statistical significant correlation
between the blur level of the adapting images and the shift in PBF
(r=0.77, p=0.003). The largest shift in PBF occurred following
adaptation to pure defocus (100B/0S: 0.32D±0.02D) and to the
bifocal pattern with the largest blur component (75B/25S: 0.19D±
0.05D) for 3 D addition. Adaptation to a 50B/50S bifocal pattern
produced the largest PBF shift (0.13D± 0.05D) for a 1.5 D addition.
None except one subject experienced significant after-effects
following adaptation to25B/75S bifocal pattern.
Conclusions: Our results suggest that subjects can adapt, to a certain
extent, to the image degradation produced by simultaneous vision
pattern, particularly to patterns with 50%Near/50%Far or 75%/25%Near or Far. A simultaneous vision simulator is a useful tool to assess
potential adaptation effects to bifocal corrections.
Figure 1: Adaptation to optical simultaneous vision blur
Commercial Relationships: Aiswaryah Radhakrishnan, None;
Carlos Dorronsoro, OEPM P201331436 (P); Susana Marcos,
OEPM P201331436 (P)
Support: FIS2011-25637; ERC-2011-AdG-294099; EU Marie Curie
FP7-PEOPLE-2010-ITN #26405
Program Number: 2906 Poster Board Number: D0005
Presentation Time: 8:30 AM–10:15 AM
Eye movements in children with delayed reading skills
Valldeflors Vinuela-Navarro1, Cathy Williams2, Jonathan T. Erichsen1,
Joy Margaret Woodhouse1. 1School of Optometry and Vision
Sciences, Cardiff University, Cardiff, United Kingdom; 2School of
Social and Community Medicine, University of Bristol, Bristol,
United Kingdom.
Purpose: Vision can be considered the primary sensory input for
development and learning, and any condition that impairs vision,
including eye movement anomalies, may reduce performance in
learning and recreational environments. The purpose of this study
is to evaluate differences in oculomotor behaviour between children
who are good/average readers and children with delayed reading
skills.
Methods: Binocular eye movement recordings were obtained from
163 children (4-11 years) using a Tobii TX300 eye tracker. A 2°
customised animated stimulus moving horizontally and vertically
at 6°/s and 12°/s was used to study smooth pursuit. A 2° cartoon
character was presented horizontally from -20° to +20° in steps
of 5° to study saccades. Velocity and position gains, the number
of saccades throughout the smooth pursuit, and the saccadic main
sequence were obtained for each participant. The children who had
delayed reading skills (n=43) were unmasked after data collection
was completed. Means and standard deviations were calculated for
children with and without delayed reading skills in each age group.
Confidence intervals for the parameters measured were obtained from
the good/average readers. Contingency tables were produced showing
the proportion of children with and without delayed reading skills
with eye movement parameters outside the established confidence
intervals.
Results: Paired t-tests showed no significant differences in the means
of any eye movement parameter studied between good/average
readers and those with delayed reading skills for any age group
(p>0.05). In contrast, the eye movement parameters of children with
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
delayed readings skills were more frequently outside the confidence
intervals for their age (smooth pursuit: 23.2%; saccades: 34.9%)
than was the case for good/average readers (8.3% and 18.3%,
respectively). Chi-square tests revealed an association between
delayed reading and parameters for horizontal smooth pursuit
(x2=6.55; p=0.01) and saccades (x2=4.94, p=0.02) that were outside
the confidence intervals.
Conclusions: Children with delayed reading skills have a two-fold
increased risk of having their eye movement properties outside
the confidence intervals for their age. Hence, there is evidence to
support an association between delayed reading and eye movements,
suggesting that some of these children may have significantly
different eye movements or their eye movements have not developed
at the same rate as typical children.
Commercial Relationships: Valldeflors Vinuela-Navarro, None;
Cathy Williams, None; Jonathan T. Erichsen, None; Joy Margaret
Woodhouse, None
Support: The College of Optometrists Postgraduate Scholarship
Program Number: 2907 Poster Board Number: D0006
Presentation Time: 8:30 AM–10:15 AM
The effect of anisometropic amblyopia on initiation of smooth
pursuit eye movements
Ivy Ziqian Liu1, Rana Arham Raashid1, Alan Blakeman3, Agnes
M. Wong2, 3. 1Department of Neurosciences and Mental Health,
Hospital for Sick Children, Toronto, ON, Canada; 2Department of
Ophthalmology and Vision Sciences, Hospital for Sick Children,
Toronto, ON, Canada; 3Department of Ophthalmology and Vision
Sciences, University of Toronto, Toronto, ON, Canada.
Purpose: Amblyopia is a spatiotemporal visual impairment caused
by abnormal visual experience early in development. Recent studies
have shown that amblyopia affects visuomotor behaviors in addition
to impairing sensory functions. Here we investigate the effects
of anisometropic amblyopia on smooth pursuit eye movements
responsible for maintaining visual acuity and stabilizing the image of
moving objects on the fovea. We hypothesized that given the visual
processing delays in amblyopia, there will be a significant delay in
the initiation of pursuit in patients during amblyopic eye viewing
Methods: Fourteen visually normal controls and 9 people with
anisometropic amblyopia were instructed to follow a red laser dot
moving at ±15/s horizontally for approximately one second for a
total of 40 trials. The experiment was repeated for each participant
under three viewing conditions in the given order: 1) amblyopic/
nondominant eye, 2) binocular, and 3) fellow/dominant eye viewing.
Outcome measures were pursuit initiation latency, open-loop gain
(eye/target velocity ratio 100 ms post-onset), and steady state gain
(eye/target velocity ratio throughout movement).
Results: As predicted, when viewing monocularly with the
amblyopic eye, participants with anisometropic amblyopia took
longer to initiate pursuit movements (203±20 ms) compared to
controls viewing with their nondominant eye (183±17 ms, p=0.004).
The pursuit latency in patients during binocular (168±17 ms) and
monocular fellow eye (176±22 ms) viewings was comparable
to controls (binocular: 172±19 ms; dominant eye: 169±15 ms
respectively). Mean open-loop gains and steady state gains did not
differ significantly between the two groups.
Conclusions: This study provides novel evidence of delayed pursuit
initiation in people with anisometropic amblyopia with the amblyopic
eye viewing. A comparable observation was made previously
in a study involving saccadic eye movements in anisometropic
amblyopia. Our findings suggest that longer initiation latencies may
be due to a delay in visual processing of target motion in amblyopia.
However, after smooth pursuit has been initiated, pursuit accuracy in
amblyopia was equivalent to that seen in visually normal participants.
Commercial Relationships: Ivy Ziqian Liu, None; Rana Arham
Raashid, None; Alan Blakeman, None; Agnes M. Wong, None
Support: CIHR MOP 106663, Leaders Opportunity Fund from the
Canada Foundation for Innovation (CFI), the John and Melinda
Thompson Endowment Fund in Vision Neurosciences, and the
Department of Ophthalmology and Vision Sciences at The Hospital
for Sick Children.
Program Number: 2908 Poster Board Number: D0007
Presentation Time: 8:30 AM–10:15 AM
Eye movement reaction times and visual task performance in
congenital nystagmus in the presence of mental load
Marzieh Salehi Fadardi, Larry A. Abel. Optometry and Vision
Science, University of Melbourne, Melbourne, VIC, Australia.
Purpose: Longer visual recognition time and latencies of target
acquisition (Lt) and saccades (Ls) have been measured in congenital
nystagmus (CN). Visually demanding tasks in the presence of
stress have been said to make CN worse. We have investigated task
performance, Lt and Ls in saccade tasks with low and high mental
load in CN and controls.
Methods: Eye movements and heart rate (HR) were recorded in 15
CN and 25 normal subjects who were required to respond manually
to saccade targets randomly presented. The task was done with low
mental load (by itself) and high mental load (with time restriction
and mental arithmetic). We compared manual response time (RT),
HR, Lt and Ls within subjects and across groups using 2-way mixed
ANOVA.
Results: High mental load was evidenced by significantly increased
in HR at both groups. The percentage of the trials with saccades
towards target did not change across tasks in CN. Eye movement
reaction times were significantly longer in CN than normals (Ls:
f(1,38)=26.3, p<.001, Lt: f(1,38)=23.12, p<.001) and also at the task
with high mental load Ls:f(1,38)=34.7, p<.001, Lt: f(1,38)=7.20,
p=.011). The interaction between task and group was not significant
for Ls (Mean ± SEM for CN: 254.6±9.9 ms at low and 221±7.4 at
high load; for normals: 216.2±6.1 at low and 180.8±4.2 at high load).
Similarly, no significant interaction was found between task and
group for Lt for CN: 539.7±47.4 at low and 489.8±20.6 at high load;
for normal: 375.6±5.8 at low and 413.1±9.3 at high load). There was
a significant main effect on manual RT only for group (f(1,38)=9.9,
p=.003). The interaction between task and group was significant for
RT; CN subjects showed longer RT than normals with high load (for
CN: 873.3±47.3 at low and 968.7±32.7 at high load; for normals:
770±25 at low and 801.1±36.6 at high load, f(1,38)=5.02, p=.03).
Conclusions: Both Ls and Lt are prolonged in CN. Task performance
degraded in CN with mental load. Possible interactions between task
demands and internal state may have affected CN and may have
changed the exposure time required to see a target. Further studies are
required to investigate the underlying motor and sensory mechanisms
involved in both being slow to get on the target and slow to recognize
it.
Commercial Relationships: Marzieh Salehi Fadardi, None; Larry
A. Abel, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 2909 Poster Board Number: D0008
Presentation Time: 8:30 AM–10:15 AM
Saccadic and optocollic head movements in homing pigeon
(Columba livia)
Jonathan T. Erichsen1, Christopher M. Dillingham1, John A. Barnes1,
Turgut Meydan2, Tomasz Kutrowski2, Noor Aldoumani2. 1Optom and
Vis Sciences, Cardiff University, Cardiff, United Kingdom; 2Wolfson
Centre for Magnetics, Cardiff University, Cardiff, United Kingdom.
Purpose: Quantitative measurement of the dynamical properties
of visuomotor movements provides useful information about the
interrelationship between the sensory capabilities of the visual system
and the control of motor responses in people and other animals. The
purposes of this study in pigeon were: 1) to define the main sequence
of saccadic head movements, and 2) characterise the nature and
thresholds of the reflexive optocollic response to an OKN stimulus.
Methods: To investigate saccadic head movements, 17 birds were
placed in a Perspex box with a transparent lid, and the angular
position of their heads was recorded with a high-speed video camera
(500fps). Both spontaneous movements and those in response to a
non-localisable auditory stimulus were measured. A second group
of birds (n=9) were gently restrained and placed in the centre of
an arena comprising 6 LCD monitors on which could be displayed
a vertical square wave (0.16 cycles/°) OKN stimulus moving at
different velocities. Head position was recorded with a digital camera
(60fps). In both experiments, horizontal head angle was determined
frame by frame with purpose-designed software using LabView.
The OKN stimuli were presented either: a) using stepped increases
(2, 4, 6, 8 or 10°/s) of velocity from 2 to 60°/s with each step lasting
10 or 20s, or b) at randomly chosen velocities (1-100°/s) that lasted
60s.
Results: The slope of the approximately linear relationship between
the peak velocity and amplitude of the pigeons’ head movements
was considerably higher for movements in response to an auditory
stimulus. Similar to humans, the duration of head movements over
a range of 7° to 70° is relatively constant and shorter in response to
sound (110ms vs 150ms). In response to the stepped OKN stimulus,
slow phases of the pigeons’ head responses had a gain close to 1 up
to a velocity of 50-60°/s, above which the gain decreased to below
0.5. In contrast, random presentation resulted in a drop in gain above
30°/s. Responses were only recruited above a velocity threshold of
5°/s. At higher velocities, attaining a gain of 1 took progressively
longer.
Conclusions: Saccadic head movements in pigeons reveal a main
sequence similar to that of head movements in humans. Ramping up
the speed of the OKN stimulus at least doubles the velocity at which
the bird achieves a gain of 1, suggesting only a limited range of
visual velocities are capable of recruiting the optocollic response.
Commercial Relationships: Jonathan T. Erichsen, None;
Christopher M. Dillingham, None; John A. Barnes, None; Turgut
Meydan, None; Tomasz Kutrowski, None; Noor Aldoumani, None
Support: Leverhulme Trust (UK)
Program Number: 2910 Poster Board Number: D0009
Presentation Time: 8:30 AM–10:15 AM
“Face” stimulus eliminates pro and anti saccade differences
Ari Z. Zivotofsky, Liran Zeligman. Brain Science, Bar Ilan University,
Ramat Gan, Israel.
Purpose: Two classic ocular motor paradigms are the pro- and
anti-saccade tasks. In the former, the subject is required to make a
saccade towards an appearing target while in the later he looks in the
opposite direction. Classically, anti-saccades result in more erroneous
saccades and longer latency saccades. We hypothesize that if the
standard symbolic cue is replaced with a “smiley” like face-drawing
rather than a typical symbolic icon it will increase the difficulty in
disengaging from fixation and eliminate those differences.
Methods: Subjects provided written, informed consent. Trials began
with a 2000 ms fixation target in the center of the screen that also
serves to indicate the saccade type: a plus sign for pro and a circle for
anti. The cue then appears (with equal probability) left or right for
600 ms. Participants are required to direct their gaze, as quickly as
possible, ‘‘TOWARDS’’ the cue (pro-saccade task) or ‘‘AWAY’’ from
the cue (anti-saccade task). Pro and anti saccades were run either
in blocks or randomly interleaved. In the drawn-face variation the
symbolic stimulus is replaced with a “smiley” like face-drawing that
signals task type and target direction.
Monocular eye movements were recorded at 120 Hz using the
ISCAN ETL-400 (ISCAN Inc., Woburn, MA) video system.
Results: 21 right-handed undergraduate students between the ages of
20 and 22 (8 males) participated in this experiment. Mean error rates
were significantly lower for pro than anti in both block (0.05 vs 0.22)
and random (0.12 vs 0.42) in symbolic conditions. No such difference
was found in face trials. A similar result was found for saccadic
latency. Mean latencies were significantly lower (p<.001) for pro
than anti in both block (249 ms vs 329) and random (260 vs 320) in
symbolic conditions. No such difference was found in face trials.
Conclusions: The seemingly ubiquitous difference between pro
and anti saccades is usually attributed to the “difficulty” inherent in
suppressing a reflexive saccade and then producing the anti saccade.
Our data, in which the pro advantage disappears in the face-type
trials points not to a typical handicap in anti- but a speeding up in
pro. When presented with face stimuli subjects have more trouble
disengaging resulting in the pro- trials showing results similar to a
typical anti- trial.
Commercial Relationships: Ari Z. Zivotofsky, None; Liran
Zeligman, None
Program Number: 2911 Poster Board Number: D0010
Presentation Time: 8:30 AM–10:15 AM
Anti-saccades in early stages of multiple sclerosis
Antonio F. Macedo5, Marisa B. Ferreira5, 3, Marta G. Parreira3, Inês
Sousa6, José Figueiredo4, João J. Cerqueira1, 2, Paulo S. Pereira6.
1
Neurosciences Domain; Life and Health Sciences Research Institute,
School of Health Sciences and ICVS/3B’s Associate Laboratory,
University of Minho, Braga, Portugal; 2Clinical Academic Centre
(CCA), Hospital de Braga, Braga, Portugal; 3TEM-All with the
Mutiple Sclerosis, Braga, Portugal; 4Department of Neurology,
Private Hospital of Braga, Braga, Portugal; 5Vision Rehabilitation
Lab.; Centre/Department of Physics and Optometry, Universty
of Minho, Braga, Portugal; 6Department of Mathematics and
Applications, University of Minho, Braga, Portugal.
Purpose: Eye movements disability is common finding in multiple
sclerosis (MS) but the exact stage at which changes are visible is not
clear. The aim of study was to assess if anti-saccade (AS) planning
and execution are altered at early stages of the disease.
Methods: A total of 48 participants with MS selected by a
neurologist (JJC) at Hospital de Braga and 52 controls participated
in this study. Inclusion criteria: relapsing-remitting course, EDSS≤3,
1 month or more without MS crisis, and normal or corrected visual
acuity. Exclusion criteria (MS and Control): cognitive impairment,
traumatic brain injury or stroke. The mean age in the MS group was
37y and 33y in the control group. Eye movements were monitored
using a binocular infrared eyetracker running at 250Hz(RED250,
SMI Gmb Germany), precision <0.4deg, stimuli were presented in a
22 monitor (Dell P2210). Code for running the experiment and data
analysis was written using the Matlab (Mathworks Inc). Participants
were seated in a room dim light at 74cm from the monitor and head
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
movements were minimized by a headband. The task was to fixate,
after a variable period between steady fixation and the stimulus of
1250ms or 1600ms, participants looked as quickly as possible for the
opposite direction where the target (a 30x30mm cross) was presented
(anti-saccade movement). Each subject performed 40 trails.
Results: The main results were the proportion of the directional
errors (wherein the participant voluntarily looked for the wrong
side), and latencies for: i) anti-saccades, ii) pro-saccades (movement
in the same direction of the stimulus) and iii) correction (reaction
time that the participant takes from the error fixation until to start
the movement). The mean number of errors was 28%(SD=19) in
MS group and 16%(SD=11) in the control group, mean difference
12%, t(74)=3.83, p<.001. Anti-saccades latency was 330msec
(SD=61) in the MS group and 294ms(SD=59) in the control group,
mean difference 36ms, F(1,98)=10.99, p<.05. The mean of the
correction latency value was 178ms(SD=111) in the MS group and
129ms(SD=107) in the control group with a mean difference of 49ms,
F(1,98)=6, p<.05. No statistically significant differences were found
in accuracy and pro-saccade latency between groups.
Conclusions: This study shows that anti-saccades latency and errors
are increased at early stages of multiple sclerosis. Anti-saccades
might be a sensitive tool to assess functional status in people with this
condition.
Commercial Relationships: Antonio F. Macedo, None; Marisa
B. Ferreira, None; Marta G. Parreira, None; Inês Sousa, None;
José Figueiredo, None; João J. Cerqueira, None; Paulo S. Pereira,
None
Support: This study was supported by the Multiple sclerosis
Association “Todos com a Esclerose Multipla (TEM)”. The Lab. of
Vision Reabilitation receives support from Shamir Portugal, FCT and
APLO
Program Number: 2912 Poster Board Number: D0011
Presentation Time: 8:30 AM–10:15 AM
Objective optokinetic nystagmus measurement in children from
consumer grade video
Jason Turuwhenua1, Mehrdad Sangi1, Benjamin Thompson2.
1
Auckland Bioengineering Institute, University of Auckland,
Auckland, New Zealand; 2Department of Optometry and Vision
Science, University of Auckland, Auckland, New Zealand.
Purpose: Accurate clinical assessment of visual function in young
children is challenging. Optokinetic Nystagmus (OKN) may allow for
objective measurement of visual function in children if appropriate
child-friendly eye tracking techniques are available.
Methods: We developed software tools to analyze video footage
of children (n = 5 children, n = 20 individual trials) freely viewing
dynamic random dot stimuli designed to elicit OKN (250 dots,
0.5° diameter, drifting at 8°/second). The videos were recorded
using an off-the-shelf video recorder (SONY digital high definition
camera HDRCX7EK, Sony Corporation, Tokyo, Japan). A novel
head stabilization technique based on tracking random features of
the face was applied to the videos to obtain a stable visualization of
the head area. This was followed by extraction of the eye velocity
in the stabilized eye region. Finally, the presence of OKN was
detected using a method in which quick phases fitting heuristic
criteria were averaged and thresholded. The outputs of our technique
were compared with the observations of two observers masked
to the results of the method. Firstly, the quick phases observed by
an experienced observer were compared to those detected by the
automated method. Secondly, the overall computer determined
assessment as to the presence of OKN in each trial was compared
with judgements made by a clinical assessor.
Results: The sensitivity and specificity of our eye movement
detection was 89.1% and 98.9% respectively across all trials, with
an experienced observer as a baseline. The positive predictive and
negative predictive values were 72.6% and 99.5% respectively. Our
OKN detection method predicted the clinical assesor’s results in 17
of 20 (85%) of the trials.
Conclusions: We developed tools that improved the visualization
of the eye, and facilitated the measurement of OKN related eye
movements from videos of children. The results suggest that
consumer grade equipment can be used for the assessment of eye
movements in children, which may help in the diagnosis of visual
disorders.
The workflow we implemented for the semi-automated detection of
optokinetic nystagmus
Commercial Relationships: Jason Turuwhenua, #60259 (P);
Mehrdad Sangi, #60259 (P); Benjamin Thompson, #60259 (P)
Support: University of Auckland Faculty Research Development
Fund
Program Number: 2913 Poster Board Number: D0012
Presentation Time: 8:30 AM–10:15 AM
Infantile Nystagmus and Abnormalities of Conjugate Eye
Movements in Down Syndrome: A Corollary of Cerebellar
Maldevelopment
Avery H. Weiss1, 2, James O. Phillips1, 3, John P. Kelly1, 2. 1Ophthal,
Roger Johnson Vis Lab, Seattle Children’s Hosp/W-7729, Seattle,
WA; 2Ophthalmology, University of Washington, Seattle, WA;
3
Otolaryngology, University of Washington, Seattle, WA.
Purpose: Anatomic and neuroimaging evidence of abnormal
cerebellar development in humans and a mouse model of DS
prompted us to study the eye movements of DS patients with CN.
Methods: Gaze-holding in primary gaze and at eccentricities of 15
degrees, saccades to horizontal or vertical target steps ranging from
5 to 25 deg, smooth pursuit of targets drifted at 10, 20 & 30s/s and
optokinetic nystagmus(OKN) in response to horizontally-oriented
square wave gratings (0.1cpd) drifted at 15,30 and 45s/s were
recorded with binocular video-oculography (SMI, Interacoustics).
Results: All patients demonstrated one or a combination of the
following gaze holding instabilities: 1) Conjugate, horizontal,
constant velocity, jerk nystagmus; 2) Conjugate, horizontal
symmetric or asymmetric pendular nystagmus; 3) Intermittent
saccadic oscillations that could be larger in one eye, or symmetric
in both eye; 4) saccadic oscilations superimposed upon nystagmus
types 1 or 2. Gains for horizontal saccades to target steps of more
than 5 deg were uniformly hypometric (Gains = 0.50-0.78 compared
to >0.80 for age-matched norms). The relationship between peak
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
saccadic velocity and saccade amplitude followed the main sequence.
Gains for vertical OKN were asymmetric in a subset of children.
Conclusions: The nystagmus and abnormalities of conjugate
eye movements observed in children with DS are consistent with
functional abnormalities of the cerebellum. The findings of dysmetric
saccades that follow the main sequence localize the underlying
abnormality to the cerebellum and exclude brainstem structures.
Sonic Hedgehog has been shown to mediate the proliferation and
anatomical organization of cerebellar granule neuronal precursor
cells. Deregulation of Sonic Hedgehog in DS may account for the
cerebellar abnormalities that underlie the congenital nystagmus and
ocular motor abnormalities.
Commercial Relationships: Avery H. Weiss, None; James O.
Phillips, None; John P. Kelly, None
Support: upported by an unrestricted grant from grant from the Peter
LeHaye, Barbara Anderson, and William O. Rogers Endowment
Funds
Program Number: 2914 Poster Board Number: D0013
Presentation Time: 8:30 AM–10:15 AM
Two dimensional analysis of horizontal and vertical pursuit
performance in infantile nystagmus
Lee Mcilreavy1, Tom C. Freeman2, Jonathan T. Erichsen1. 1School of
Optometry and Vision Sciences, Cardiff University, Cardiff, United
Kingdom; 2School of Psychology, Cardiff University, Cardiff, United
Kingdom.
Purpose: Previous studies of pursuit in infantile nystagmus (IN)
have generally overlooked the ability to pursue targets moving
vertically, presumably because the oscillation accompanying IN
is predominantly horizontal. We compared horizontal and vertical
pursuit in IN and controls, in each case analysing both the horizontal
and vertical components of the eye movements in order to obtain 2D
performance measures.
Methods: Fifteen adult participants with IN completed a monocular
pursuit task, with normally sighted age-matched participants as
a control. Horizontal and vertical pursuit was to a 0.2° green dot
moving through primary position with a total excursion of 16°
or 32° at velocities of either 8°/s or 16°/s. Eye movements were
recorded at 1000Hz (EyeLink 1000) and analysed offline. After
removing saccades and fast phases (IN), eye velocity relative to the
pursuit target was used to obtain 2D probability density functions.
Isocontours bounding 68% of the highest probability densities
estimated velocity matching. Accuracy was defined as isocontour
centre of mass, while precision was defined as isocontour area.
Principal component analysis of isocontour bounded data yielded
major and minor axes of the area and its shape.
Results: Results to date indicate pursuit precision was significantly
lower along both orientations for IN compared to controls (vertical
p<0.001, horizontal p<0.001). While the IN group showed large
variation, especially for accuracy, horizontal pursuit precision
was significantly greater than vertical (p<0.001) for IN, with no
significant difference in controls. Isocontour area was significantly
more circular for vertical than horizontal pursuit (p<0.001) for both
IN and controls. Further analyses of IN data may reveal the influence
of the null zone, if any, on velocity matching during pursuit as well as
the role of fast phases in re-establishing pursuit.
Conclusions: We present a novel method for investigating IN slow
phase velocity matching to a pursuit target. Our results suggest
that pursuit performance in IN is neither accurate nor precise when
compared with controls, with significant impairment for vertical
pursuit compared with horizontal.
Instantaneous eye velocities, relative to the pursuit target, for a
participant with IN. Superimposed upon the 2D scatter plot is the
corresponding probability density function of eye velocity, with
colour coding of the velocity probabilities.
Commercial Relationships: Lee Mcilreavy, None; Tom C.
Freeman, None; Jonathan T. Erichsen, None
Support: BBSRC (UK)
Program Number: 2915 Poster Board Number: D0014
Presentation Time: 8:30 AM–10:15 AM
Onset of low-frequency, upgaze-evoked and high-frequency,
horizontal nystagmus in infant with night-blindness associated,
transient, tonic downgaze (NATTD)
Huibert J. Simonsz1, 2, M. Kooiker3, J. J. Pel3, M. M. van Genderen4,
Ralf Florijn2, L.S. Smit5, Maarten Kamermans2, J. van der Steen3.
1
Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands;
2
Netherlands Institute for Neuroscience, Amsterdam, Netherlands;
3
Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands;
4
Bartiméus Institute for the Visually Impaired, Zeist, Netherlands;
5
Pediatric Neurology, Erasmus Medical Center, Rotterdam,
Netherlands.
Purpose: In 1994 we described infants who presented at age
2-4 months with tonic downgaze, chin-up head posture and lowfrequency, upgaze-evoked nystagmus that disappeared at age 2,
accompanied by high-frequency, horizontal nystagmus that persisted.
In most of these, abnormal ERGs and CACNA1F, NYX or GPR179
mutations confirming CSNB were found. As the proteins affected by
these mutations reside on either side of the rod-ON-bipolar synapse,
and this pathway carries a motion signal, this specific combination
of horizontal and vertical nystagmus may have a retinal cause. Early
diagnosis of NATTD now permits longitudinal recording of the onset
of upgaze-evoked and horizontal nystagmus.
Methods: A 4-months-old male infant, born prematurely (34 weeks,
2100g) presented with tonic downgaze and chin-up head posture.
Eye movements were recorded with a Tobii X60 video eye tracker.
Recording was repeated every 2 weeks from onset, later every 4-6
weeks. ERG was made in the months after.
Results: A hemizygote mutation c.1784G>A; p.(Arg595His) was
found in the CACNA1F gene. At 4 months (corrected age 11 weeks)
the eyes were continuously in downgaze. Upper eyelid retraction
occurred periodically without upward saccades. Slow horizontal
pendular eye movements, disjugate and more pronounced in the
right eye (Fig. 1), were accompanied by convergence spasms. At 4,5
months (corrected age 13 weeks) the horizontal pendular nystagmus
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
had become more rapid with less convergence spasms. At 5,5 months
(corrected age 17 weeks) horizontal eye movements had become
more conjugate (Fig. 2); convergence spasms were rare. The infant
occasionally tried to look ahead resulting in upward jerks with
subsequent slow phases with deceleration back to downgaze, and
eyelid retraction.
Conclusions: Tonic downgaze, accompanied by chin-up head
posture, occurred as the primary event. The horizontal pendular
nystagmus started with a minimal, hardly noticeable, pendular eye
movement. A few weeks later upgaze-evoked nystagmus started
when the infant tried to look ahead. In previous NATTD cases the
upgaze-evoked nystagmus disappeared at around 2 years, in one case
before 8 months. Interestingly, two of these were operated at age 10
for chin-down head posture, with the nulzone of the rapid horizontal
nystagmus in upgaze.
Eye movements at 11 weeks corrected age
Eye movements at 17 weeks corrected age
Commercial Relationships: Huibert J. Simonsz, None; M.
Kooiker, None; J. J. Pel, None; M. M. van Genderen, None; Ralf
Florijn, None; L.S. Smit, None; Maarten Kamermans, None; J.
van der Steen, None
Support: Foundation ODAS
Program Number: 2916 Poster Board Number: D0015
Presentation Time: 8:30 AM–10:15 AM
Dramatic Fixation Instability in Peripheral Vestibulopathies
without Visual Feedback Compared with Central
Vestibulopathies
Jaclyn Hwang, Yaping J. Liao. Ophthalmology, Stanford, Stanford,
CA.
Purpose: Eye movement abnormalities are common in central
and peripheral vestibulopathies, and characterization of eye
movements can help teach us important ways to localize the lesion.
Eye movement characterization has also been used to triage dizzy
patients in the acute setting to determine if this may be an emergency
requiring brain imaging (Kattah, Stroke, 2009). In this study, we
compared and contrasted eye movement findings during a simple
fixation task in patients with central and peripheral vestibulopathies.
Methods: We performed detailed neuro-ophthalmic examination
in 10 patients with peripheral and 10 patients with central
vestibulopathies. We assessed visual fixation with and without visual
feedback using 60-Hz binocular 3D infrared oculography. Fixation
target at distance in the light was displayed using a custom-made
LED board. Fixation target in the dark was displayed within the
infrared recording goggle and turned on and off to assess rapid
changes in eye position.
Results: In patients with peripheral vestibulopathies, such as
acoustic neuromas or vestibular neuronitis, visual fixation of a
distant target was typically good, with rare, small amplitude square
wave jerks that were also found in normals. Once fixation target was
removed, however, patients’ fixation often rapidly decompensated,
exhibiting deviations of eye positions, often in square wave jerk
waveform that may be accompanied by a torsional nystagmus. The
fixation instability pattern was different in patients with central
vestibulopathies, such as Wallenberg syndrome or brainstem
cavernous malformations. With visual feedback, patients typically
exhibited uni- or multi-directional oscillations initiated by a slow
phase. Once fixation target was removed, patients exhibited relatively
less change in eye movement waveforms during fixation.
Conclusions: We confirmed previously reported unmasking of
fixation instability in the dark without visual feedback in peripheral
vestibulopathies (Hirvonen, Eur Arch Otorhinolaryngol, 2012) and
showed that fixation in central vestibulopathies was less affected by
visual feedback, consistent with failure of fixation suppression in
central causes. We propose that a useful test to distinguish peripheral
and central vestibulopathies is to observe patient eye movement
behavior during fixation with and without visual feedback, ideally in
the dark.
Commercial Relationships: Jaclyn Hwang, None; Yaping J. Liao,
None
Support: Burroughs Wellcome Foundation
Program Number: 2917 Poster Board Number: D0016
Presentation Time: 8:30 AM–10:15 AM
Study of fusional convergence using eye tracking: preliminary
results on subjects with normal binocular vision
Michela Fresina1, Laura Cercenelli2, Cecilia Benedetti1, Emilio C.
Campos1, Barbara Bortolani2, Brunella Merante2, Piera Versura1,
Emanuela Marcelli2. 1DIMES, Ophthalmology Service, Bologna,
Italy; 2DIMES, Laboratory of Bioengineering, Bologna, Italy.
Purpose: In the field of ophthalmology, vision researchers use eye
tracking to study oculomotor behavior, cognitive visual function and
vision deficiencies. Fusional vergence is a disjunctive movement
of the eyes that is made in order to obtain single vision with two
eyes. Fusional vergence disorders are often associated with the
most common forms of strabismus. The aim of the study was to
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
characterize fusional convergence response in subjects with normal
binocular viewing by using an eye tracking system.
Methods: Base-out horizontal prisms of 4 and 6 diopters were
used to elicit fusional convergence of the right eye in 11 subjects
with normal binocular vision. Eye movements were continuously
recorded using the Viewpoint infrared video eye tracker (Arrington
Research, Scottsdale, AZ, USA) and custom software was developed
to automatically analyze off-line the saccadic response (gaze angle
and angular velocity). The Fusional Convergence Amplitude (FCA)
was calculated by subtracting the baseline position of the right eye
(i.e. before the introduction of the prism) from the maximum saccadic
excursion of the right eye during the disconjugate eye movements in
the vergence phase (Figure 1.a).
Results: The typical eye-movement response in subjects achieving
the fusional convergence was a preliminary saccadic movement of
both eyes (version phase) followed by a convergence movement
with the eyes moving towards each other to achieve single vision
(vergence phase) (Figure 1). Eye tracking recordings showed that
2 patients were not able to achieve fusion with neither 4 nor 6
diopters prisms. Fusion was achieved in 8 subjects when using the 4
diopters prism and only in 6 subjects when using 6 diopters prism.
One patient was excluded from the analysis because the saccadic
movements were highly affected by blink artifacts. The FCA varied
from 2.2°±0.2 to 3.0°±0.2 when increasing prism diopters from 4 to 6
(Figure 2).
Conclusions: The fusional convergence can be accurately studied
and evaluated using an eye tracking system. Preliminary results on
subjects with normal vision showed that when increasing the prism
diopters the fusional convergence ability decreases.
Commercial Relationships: Michela Fresina, None; Laura
Cercenelli, None; Cecilia Benedetti, None; Emilio C. Campos,
None; Barbara Bortolani, None; Brunella Merante, None; Piera
Versura, None; Emanuela Marcelli, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 2918 Poster Board Number: D0017
Presentation Time: 8:30 AM–10:15 AM
Influence of textured backgrounds on fusional vergence:
preliminary results using an eye tracker
Cecilia Benedetti1, Emanuela Marcelli2, Michela Fresina1, Emilio
C. Campos1, Barbara Bortolani2, Guido Tiberi2, Piera Versura1,
Laura Cercenelli2. 1DIMES, Ophthalmology Service, Bologna, Italy;
2
DIMES, Laboratory of Bioengineering, Bologna, Italy.
Purpose: The vergences ensure and maintain binocular fixation
and binocular vision. The amplitude of vergences depends on
many factors, one of which is the amount of fusible material on
the binocular field of vision. In casual seeing the whole surface of
the two retinas is exposed to similar stimuli and the conditions for
motor fusion should be optimal. The retinal periphery is a powerful
factor in production of fusional movements and makes an important
contribution to stabilization of relative position of the eyes.
The purpose of the study was to evaluate whether the presence of
a textured background in the visual stimulus may influence the
convergence fusional response.
Methods: Eleven subjects with normal binocular vision underwent
fusional disparity stimuli: a base-out prism of 6 diopters was placed
in front of the right eye to elicit disparity. Eye movements were
continuously recorded using the Viewpoint infrared video eye tracker
(Arrington Research, Scottsdale, AZ, USA) and a custom software
was developed to automatically analyze off-line the saccadic response
(gaze angle). Each subject was examined twice, once by presenting
the visual stimulus (black dot) on a white background, then by
presenting the same stimulus on a textured background (Figure 1).
The order of presentation of the two tests was randomly chosen.
Results: Eye tracking recordings showed a typical pattern for the
fusional behavior: a preliminary saccadic movement of both eyes
(version phase) and a following convergence movement with the eyes
moving towards each other to achieve single vision (vergence phase)
(Figure 2.a).
When presenting the stimulus on the white background only
6 subjects (54%) achieved fusional convergence. This number
increased up to 9 subjects (82%) when presenting the same stimulus
on the textured background (Figure 2.b).
Conclusions: The fusional vergence response can be accurately
studied and evaluated using an eye tracker. In subjects with normal
binocular vision the presence of a textured background seems to
facilitate the fusional convergence ability.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
was still visible, prompting a button press. Eye-tracking data were
obtained from the left eye while 205-channel, 512-Hz scalp EEG data
were recorded. We studied event-related potentials (ERPs) timelocked to saccade events for the time courses of 650 localizable ICs
assigned to 16 clusters.
Results: Mean response accuracy was 92% (SD: 5%) with mean
false positive rate 6% (SD: 4%). Mean reaction time was 1579 ms
(SD: 235 ms). After excluding 3 frontal EOG clusters comprising
240 ICs, the major (90 ms) lambda response peak in the fixationonset locked ERPs was dominated by 3 occipital IC clusters (100
ICs, 92% of the peak scalp map accounted for) (Figure 1). ERPs time
locked to saccade onsets contained a pre-saccadic spike peaking at
-12 ms. Three far frontal clusters dominated this spike (260 ICs, 95%
variance accounted) (Figure 2 left). However, after removing all 5
EOG and far frontal clusters (314 ICs) and 1 temporal scalp muscle
(EMG) cluster (26 ICs), 4 posterior clusters (114 ICs) contributed
82% of the remaining (positive-going) pre-saccadic spike (Figure 2
right).
Conclusions: ICA clustering analysis revealed multiple sources
of the lambda response and pre-saccadic spikes. Posterior cortical
contributions to the pre-saccadic spike might index corollary
suppression of visual cortex during saccades. We plan to use this task
to investigate functional vision in glaucoma patients.
Commercial Relationships: Cecilia Benedetti, None; Emanuela
Marcelli, None; Michela Fresina, None; Emilio C. Campos, None;
Barbara Bortolani, None; Guido Tiberi, None; Piera Versura,
None; Laura Cercenelli, None
Program Number: 2919 Poster Board Number: D0018
Presentation Time: 8:30 AM–10:15 AM
Source-resolved EEG analysis of human saccade-event related
potentials
Makoto Miyakoshi1, Scott Makeig1, Carolina Gracitelli3, 4, Ricardo
Y. Abe3, 2, Alberto Diniz-Filho3, 5, Saif Baig3, Felipe A. Medeiros3.
1
SCCN, Inc, University of California San Diego, La Jolla, CA;
2
Ophthalmology, University of Campinas, Campinas, Brazil;
3
Visual Performance Laboratory, Department of Ophthalmology,,
University of California San Diego, La Jolla, CA; 4Ophthalmology,
Federal University of São Paulo, São Paulo, Brazil; 5Department
of Ophthalmology and Otorhinolaryngology, Federal University of
Minas Gerais, Belo Horizonte, Brazil.
Purpose: We developed an active visual search task in which
participants saccade freely across an evolving display of Gabor
patches. Here we report the results from the EEG analyses of
saccade-related brain/muscle potentials using independent component
analysis (ICA) and independent component (IC) clustering.
Methods: Participants were 16 healthy young adults (8 female, mean
20.8 years, SD 2.8, range 18-26). Five Gabor patches were always
present on a gray background (20-inch LCD monitor at 60 cm ). A
sequence of 1200 patches were pseudo-randomly selected from four
patch sizes and five orientations (SOA 2 sec, duration 5 sec). The
task was to detect infrequent (15%) instances in which the size and
orientation of the newest patch matched those of another patch that
Figure 1. Lambda response. Occipital IC source clusters of the
lambda response following fixation onsets.
Figure 2. Pre-saccadic spike. Left, EOG/far frontal source
contributions are dominant. Right, posterior brain source
contributions remaining after removing EOG and EMG ICs.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Commercial Relationships: Makoto Miyakoshi, None; Scott
Makeig, None; Carolina Gracitelli, None; Ricardo Y. Abe, None;
Alberto Diniz-Filho, None; Saif Baig, None; Felipe A. Medeiros,
Alcon Laboratories Inc (F), Alcon Laboratories Inc (R), Allergan Inc
(C), Allergan Inc (F), Allergan Inc (R), Bausch & Lomb (F), Carl
Zeiss Meditec Inc (C), Carl Zeiss Meditec Inc (F), Carl Zeiss Meditec
Inc (R), Heidelberg Engineering Inc (F), Merck Inc (F), National
Eye Institute (F), Novartis (C), Reichert Inc (F), Reichert Inc (R),
Sensimed (F), Topcon Inc (F)
Program Number: 2920 Poster Board Number: D0019
Presentation Time: 8:30 AM–10:15 AM
Tactile acuity determined with vibration motors for use in a
sensory substitution device for the blind
H. Christiaan Stronks1, 2, Daniel J. Parker1, Nick M. Barnes1, 3.
1
Computer Vision, NICTA Canberra Research Laboratory, Canberra,
ACT, Australia; 2Neuroscience, Australian National University,
Canberra, ACT, Australia; 3College of Engineering and Computer
Science, Australian National University, Canberra, ACT, Australia.
Purpose: We aim to construct a back-worn tactile substitution device
for the blind that redirects camera images to a vibrotactile display. To
establish a feasible between-motor distance we have determined the
vibrotactile acuity on the lower back. In addition, we have established
what the impact of experience is on tactile acuity using an active
learning procedure.
Methods: This study included 15 healthy subjects. Vibrational
stimuli (100-ms stimulations) were delivered by coin motors
(Precision Microdrives, LLC) with a diameter of 12 mm (Stronks et
al., Artif Organs. in press). The motors were mounted on a carrier of
urethane at various between-motor spacings (Fig. 1). Tactile acuities
were determined with an adaptive, 2-alternative forced choice
task using various offsets (0 – 200 ms) between two successive
motor activations (n= 12). Training effects (n= 3) were tested at a
stimulation offset of 0 ms. Subjects received 30 minutes of practice
with feedback after each trial. Acuity tests were done before, during
and after training.
Results: Average tactile acuities varied from 36 to 63 mm center-tocenter, dependent on stimulus offset. The least favorable acuities were
found when the vibrational stimuli were presented simultaneously
(offset 0 msec). Acuities at the longest offset tested (200 ms)
significantly differed from those at 0 ms and were 41 mm on average
(RM ANOVA and Tukey’s post hoc test; P< 0.05). Acuities at
intermediate offsets (50 - 175 ms) did not differ significantly from
those obtained at 0 and 200 ms. The correlation between acuity and
offset time approached significance (linear regression and F-test,
P= 0.07). After practice, two subjects improved by 30% and 90%,
respectively, while one subject performed 10% worse. The average
improvement was 35%.
Conclusions: Based on the regression analysis, the interpolated
tactile acuity at 200 ms stimulus offset was 42 mm center-to-center.
Preliminary results showed that subjects improved after practice. This
suggests that after training motor spacings of 32 mm may be effective
for use in a vibrotactile display, provided that adjacent motors are
stimulated with an offset of 200 ms.
Fig. 1. Experimental setup. (A) Subject with mounted motors. (B)
Urethane carrier with motors. (C) Schematic showing between-motor
distances. (D) Circuit board driving the motors. (E) Available motor
spacings.
Commercial Relationships: H. Christiaan Stronks, None; Daniel
J. Parker, None; Nick M. Barnes, None
Program Number: 2921 Poster Board Number: D0020
Presentation Time: 8:30 AM–10:15 AM
The Dobson Card: An electronic display for forced-choice
preferential looking (FPL) assessment of infant and toddler visual
acuity
Joseph M. Miller1, 2, Howard P. Apple1, 3, Tina K. Green1, Deborah
Apple3, Erin M. Harvey1. 1Ophthal & Vision Science, University of
Arizona, Tucson, AZ; 2College of Optical Sciences and College of
Public Health, University of Arizona, Tucson, AZ; 3Apple Medical
Incubator, Winter Park, FL.
Purpose: To determine if the looking behavior of infants and toddlers
during Acuity Card Procedure (ACP) testing using electronic stimuli
is similar to the behavior observed when printed stimuli are used.
Methods: A trained and experienced Teller Acuity Card tester
measured binocular grating acuity in 8 subjects aged 9 to 45 months.
Stimuli were presented using The Dobson Card (DC), a hand-held
matt-black plexiglass frame (10”x22”) that flush-mounts 2 Google
Nexus-7 (N7) tablet computers to the right and left of a center
peephole. One tablet displays a square wave grating (1/2 octave
steps), the other a luminance-matched gray patch. Stimuli were
generated using Java language. An experimenter luminance matched
the 2 tablet gray patches, then matched gratings to the paired gray
patch. The gray patch and paired grating had a luminance of 92 lux,
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
and widest white stripe 170 lux (Dr Meter LX1330B photometer). An
assistant controlled the tablet displays via Bluetooth to preserve tester
masking of grating location and permit standard ACP testing. The DC
was presented in a ACP stage (Vistech Consultants).
Results: All subjects looked at the gratings in a manner similar to
TAC. However, observed acuities were low normal/below normal
when compared to published norms obtained with the printed Teller
Acuity Cards (Vistech Consultants, Inc., TAC II now manufactured
by StereoOptical). Acuity ranged from 2.4 to 18.2 Cy/Deg (cpd),
median 5.65 cpd, mode 4.8 cpd.
Conclusions: Children exhibit interest in viewing patterns of black
and white stripes over gray control stimuli presented using tablet
computers set against a black background in a manner similar to
printed gratings against a gray background. The tasks differ, as
the tablet requires comparison and cards detection. Acuities were
below those expected for children of the same age using printed
stimuli. Further work is required to determine the optimum stimulus
luminance and background illumination, and normative data for
DC acuity will need to be generated. Previous work has shown
that even different versions of printed acuity cards yield different
norms (Vistech vs Stereo Optical cards, Haynes et al., ARVO 2004).
While static square wave gratings are used in this initial evaluation,
the Dobson Card can be used for the display of a variety of stimuli
such as alternating checkerboards or displays of coherent motion vs
random motion.
Commercial Relationships: Joseph M. Miller, None; Howard P.
Apple, None; Tina K. Green, None; Deborah Apple, None; Erin
M. Harvey, None
Support: NEI/NIH EY13153 (EMH), Research to Prevent Blindness
(RPB) Career Development Award (EMH), RPB Center Award
(JMM)
Program Number: 2922 Poster Board Number: D0021
Presentation Time: 8:30 AM–10:15 AM
Enhancing tolerance of image motion through perceptual
learning: Static and dynamic bisection acuity
Kenneth D. Tran1, Charlie Ngo1, John Bui1, Esther Yang1, Dennis
M. Levi1, 2, Roger W. Li1, 2. 1School of Optometry, University of
California-Berkeley, Berkeley, CA; 2Helen Wills Neuroscience
Institute, University of California-Berkeley, Berkeley, CA.
Purpose: Our previous findings show that practice can substantially
improve dynamic bisection acuity. However, since the stimulus
exposure time (300 ms) was longer than the latency for saccadic eye
movements, the improved acuity could have been merely the result
of improved tracking eye movements. In the present experiment,
we used a shorter stimulus duration (150 ms) in order to isolate the
effects of perceptual learning on motion processing.
Methods: The bisection stimulus comprised of three briefly presented
black square dots (duration 150ms) separated by 5 arcmin. The
observer’s task was to localize the position of the central dot relative
to the adjacent dots. On day 1, the pre-training session consisted of 5
stimulus conditions: [1] static horizontal orientation, [2] static oblique
(45 deg) orientation [3] oblique stimulus moving in an orthogonal
direction (135 deg) at 1.33 deg/s, and [4-5] oblique stimulus moving
along a 45 degree trajectory at two different speeds (1.33 & 2 deg/s).
Observers practiced the task with the static oblique stimulus from
day 2 to 8, subsequently with the moving oblique stimulus (2 deg/
sec) from day 10 to 16. Performance for all five conditions was reevaluated in two post-training sessions on days 9 and 17.
Results: Bisection acuity improved dramatically (35%) after
practicing with the static oblique stimulus. Learning transferred
substantially to the untrained static horizontal stimulus (26%
improvement) and the three untrained moving oblique stimuli
(1.33 deg/s along 135 deg, 34% improvement; 1.33 deg/s along 45
deg, 31% improvement; 2 deg/s along 45 deg, 17% improvement).
Subsequent practice with the oblique stimulus in motion (2 deg/s)
resulted in a further 37% improvement in dynamic bisection acuity
(a total of 47% from day 1), and the performance for lower speed
stimuli improved as well.
Conclusions: Our findings suggest that perceptual learning enhances
tolerance of image motion. We characterized the specificity of
learning a bisection acuity task and showed that the learning
generalizes substantially, but not completely, from static to moving
stimuli, and across different stimulus speeds and orientations.
Commercial Relationships: Kenneth D. Tran, None; Charlie Ngo,
None; John Bui, None; Esther Yang, None; Dennis M. Levi, None;
Roger W. Li, None
Support: NH Grant R01EY01728
Program Number: 2923 Poster Board Number: D0022
Presentation Time: 8:30 AM–10:15 AM
Effect of crowding on postural control
Guillaume L. Giraudet2, 1, Marion Grun1, Jocelyn Faubert1.
1
Psychophysics & Visual Perception Lab, Universite de Montreal,
Montreal, QC, Canada; 2R&D, Essilor Canada, Montreal, QC,
Canada.
Purpose: The aim of the current study was to determine the effect
of foveal crowding on postural stability in young adults and elderly.
Crowding describes the deleterious influence of neighboring objects
(flankers) on the recognition of a central target.
Methods: Thirty-three subjects participated in the experiment: 20
young adults and 13 elderly. They stood, barefoot and arms crossed,
in front of a projection screen. Optical motion sensors, located on a
helmet, and 6 IR cameras (Optotrak system) were used to track and
register head movements during trials. Each trial lasted 64s. The
stimulus displayed on the screen was a black and white checkerboard
with an empty grey area (5° of visual angle) in front of the subject’s
eyes. This peripheral checkerboard could be either static or in motion.
Four different tasks, proposed in different orders, were considered:
i) subjects were instructed to look at a fixation point, located in the
middle of the central empty area; ii) subjects had to find target letters
within RSVP sequences of letters; iii) and iv) both last tasks were
the same as the second one but with flankers in the periphery, far
from (task 3 – low crowding) or close to (task 4 – high crowding)
the central letters. Each trial was repeated 3 times. We calculated
the Velocity Root Mean Square (VRMS) of head movements based
on the signal provided by the optical sensors. VRMS represented
a measure of postural instability induced by the various visual
conditions and tasks.
Results: Results showed that subjects were more stable when they
had to fixate the central point (task1) than when they were instructed
to find target letters within RSVP sequences (tasks 2, 3 and 4).
However, the change of postural behavior as a function of the task
was significantly different between both young adults and elderly
groups. While the former maintained the same level of stability for
the 4 tasks, the latter was significantly affected by the RSVP tasks
and crowding.
Conclusions: Some previous studies showed that visual crowding
increased with age, older people being more disrupted than young
adults when the target to be recognized is surrounded by flankers
(Scialfia et al, 2012 for review). Our experiment also showed that
the effect of letter recognition and crowding on postural stability was
higher for the elderly. The attentionnal load needed to perform letter
recognition tasks, leaving fewer resources for the good control of
postural stability, might explain this result.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Commercial Relationships: Guillaume L. Giraudet, Essilor
Canada (E); Marion Grun, None; Jocelyn Faubert, None
Support: NSERC-ESSILOR Industrial Chair
Program Number: 2924 Poster Board Number: D0023
Presentation Time: 8:30 AM–10:15 AM
The Effect of Room Length on Perceived Egocentric Distance in
Darkness
Susan A. Kelly. Basic Science, Illinois College of Optometry,
Chicago, IL.
Purpose: In the dark the perceived egocentric distance of a selfilluminated target has been reported to be underestimated by a
number of laboratories. This underestimation is of about the same
magnitude whether perceived distance is measured using a verbal
magnitude estimation task or a blind-walking motor task. We have
investigated the effect of the room dimensions on the perceived
egocentric distance and found this variable to be significantly affected
by room length.
Methods: Two groups of visually normal subjects were tested, all of
whom had an eye exam within the past year. One group was tested in
a room 3.8m wide and 8m long (n=20). The other group was tested
in a room 11m wide and 9m long (n=15). Subjects clearly viewed the
testing space prior to the testing session.
After obtaining informed consent, subjects were instructed to
monocularly observe the perceived distance and height of a small,
self-illuminated, red target placed on the floor of an otherwise dark
room. The target was randomly located at 4 distances between 1.5
and 7.5m. When ready subjects occluded their eye and blind-walked
to the remembered target location. They indicated with the tip of their
index finger the perceived target height.
Results: A two-way analysis of variance (mixed design) was used
to compare the perceived distances for the two testing spaces (IBM
SPSS). The interaction effect of Distance*Room was significant
(F=7.48, p<0.000). Independent t tests with Bonferroni correction
indicated that perceived target distances varied significantly between
testing spaces except at 1.5m. The best-fit power function exponents
for the two spaces are listed below, along with those obtained from
previously published data (width x length in m):1) Philbeck and
Loomis (1997) 4.3x7.3; 0.54 2) Kelly (2014) 3.8x8; 0.67 3) Kelly
(2014) 11x9; 0.89 4) Philbeck and Loomis (1997) 1.8x18; 0.89.
Conclusions:
1. The perceived distance is significantly foreshortened when
measured in a shorter room than in a longer testing space.
2. The perceived height of self-illuminated target is significantly
higher in a shorter room than in a longer testing space.
3. The exponent for perceived distance is smaller the shorter the
testing space, indicating spatial compression occurs more in short
rooms.
4. There are a number of potential explanations for this effect which
will be discussed.
Commercial Relationships: Susan A. Kelly, None
Program Number: 2925 Poster Board Number: D0024
Presentation Time: 8:30 AM–10:15 AM
A Novel Testing Paradigm for Assessing Eye Movements during a
Visual Task
Timo Melman1, 2, Alberto Diniz-Filho1, 3, Erwin R. Boer1, 2, Ricardo Y.
Abe1, 4, Carolina Gracitelli1, 5, Saif Baig1, Felipe A. Medeiros1. 1Visual
Performance Laboratory, Department of Ophthalmology, University
of California San Diego, La Jolla, CA; 2Department of Mechanical
Engineering, Delft University of Technology, Delft, Netherlands;
3
Department of Ophthalmology and Otorhinolaryngology, Federal
University of Minas Gerais, Belo Horizonte, Brazil; 4Department
of Ophthalmology, University of Campinas, Campinas, Brazil;
5
Department of Ophthalmology, Federal University of São Paulo, São
Paulo, Brazil.
Purpose: To evaluate a new test paradigm for saccadic and smooth
pursuit eye movement performance during an attentional and visual
performance-based task.
Methods: Subjects underwent three tests to assess saccadic and
smooth pursuit eye performance. In each test the subject performed
20 saccades. In each trial a square with 3 possible different levels of
contrast was presented in the middle of a LCD screen. Saccadic eye
movements were induced by new squares appearing randomly every
3-6 seconds around the initial square. Subjects were instructed to
fixate the new target as quickly as possible. If a successful fixation
was observed the square disappeared. In the first test one new target
appeared each time. In the second test two targets of different sizes
appeared and the subject was instructed to move the eyes towards
the smaller target as quickly as possible. In the third test, two equal
sized squares appeared, but one of the two squares was displayed
with a 0.1 second delay. The eye movements were synchronized
with the test dynamics during each performance test using the SMI
Eye Tracking Glasses (SensoMotoric Instruments GmbH, Teltow,
Germany). Free head movements were allowed in order to establish
natural movements of the eye-head complex. The influence of
different contrast levels on the latency of saccadic eye movement was
assessed. Reaction time, maximum saccade velocity, number of initial
direction errors, and settling time were used as metrics.
Results: Five healthy subjects with mean age of 39.8 ± 18.4 years
(range: 18 – 60 years) were included. There was a strong and positive
correlation between mean reaction time and age (P = 0.002). The
results also showed a significant negative correlation for age and
number of initial direction errors (P = 0.050).
Conclusions: These preliminary results showed an age-relateddegradation in saccadic reaction in response to a visual task and
in number of initial direction errors in normal participants. An
explanation could be that older subjects use a more top down method
to perform the experiment, where younger people use the faster
bottom up method instead. The proposed paradigm with free head
movements may help integrate the study of eye movements and
visual performance for evaluation of diseases such as glaucoma.
Commercial Relationships: Timo Melman, None; Alberto
Diniz-Filho, None; Erwin R. Boer, None; Ricardo Y. Abe, None;
Carolina Gracitelli, None; Saif Baig, None; Felipe A. Medeiros,
Alcon Inc (F), Alcon Inc (R), Allergan (F), Allergan (R), Bausch &
Lomb (F), Carl Zeiss Meditec Inc (C), Carl Zeiss Meditec Inc (F),
Carl Zeiss Meditec Inc (R), Heidelberg Engineering Inc (F), Merck
Inc (F), National Eye Institute (F), Novartis (C), Reichert Inc (F),
Reichert Inc (R), Sensimed (F), Topcon Inc (F)
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 2926 Poster Board Number: D0025
Presentation Time: 8:30 AM–10:15 AM
Action game training only modifies game-related visual search
strategies
Elham Azizi, Matthew Stainer, Larry A. Abel. Optometry and Vision
Scineces, University of Melbourne, Melbourne, VIC, Australia.
Purpose: Action video game playing has been shown to modify
several parameters of cognitive processing. One key question is how
changes that are often measured with abstracted paradigms relate
to visual behavior outside the laboratory. We investigated the effect
of action game training on visual search in abstract, naturalistic
(counting the number of people in city street photos) and gamerelated search tasks, to examine how changes extend beyond gamerelevant tasks.
Methods: 40 non-gamers (20 female, 17-35 years old) were trained
for 10 hours on an action game (first person shooter) or a computerbased card game (control group). Eye movements were recorded
pre- and post-training in 5 different visual search tasks: conjunctive
search for a singleton, counting people in city photos, counting
soldiers in action game photos and finding a gabor patch embedded
in the city and action game photos. Repeated measures ANOVAs
were conducted for each task with the game type (action or card)
as between and session (pre or post) as within-group independent
variables, and saccade amplitude, fixation duration, distribution of
fixations and search time as dependent variables.
Results: There was no main effect of session, game type and no
interaction for saccade amplitude or fixation duration in any of the
tasks; however, there was a main effect of game type (F1, 73 = 4.86,
p=0.046) in the vertical distribution of fixations, but only in the
soldier counting task. Action gamers showed a significant reduction
in their vertical distribution of fixations after training, but there
was no main effect of session (p=0.16) and no interaction (p=0.1).
Repeated measures ANOVA on search time showed a significant
main effect of session (F1, 74 =4.43, p=0.03) and game type (F1,
= 6.152, p=0.01) of finding the gabor in game and city photos
74
respectively.
Conclusions: After 10 hours of action gaming, participants learned
to search game images differently, with the vertical distribution of
fixations approaching that in the natural scenes. However, there
was no effect of training on searching the naturalistic scenes. Faster
detection of gabor patches in game and city scenes can be attributed
to a test-retest effect rather than training effect, as it happened in both
groups. A crucial direction for future research is to better understand
how skills enhanced in gaming can also be improved in natural
settings.
Commercial Relationships: Elham Azizi, None; Matthew Stainer,
None; Larry A. Abel, None
Program Number: 2927 Poster Board Number: D0026
Presentation Time: 8:30 AM–10:15 AM
Validation of the King-Devick Test Using 500-Hz Binocular
Infrared Oculography
M Ali Shariati1, Ming-Hui Sun2, 1, Yaping J. Liao1. 1Ophthalmology,
Stanford School of Medicine, Palo Alto, CA; 2Ophthalmology, Chang
Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan.
Purpose: Eye movement abnormalities are common in different
neuro-ophthalmic conditions. Many eye movement measures use
saccades and smooth pursuit tasks are used as markers of head
trauma, and the King-Devick Test has been well used in studying
head trauma in football, hockey, and other sports. In this study, we
used 500-Hz infrared eye tracker to validate the hand-held KingDevick Test.
Methods: We performed the hand-held or computer King-Devick
test using 500-Hz binocular 2D infrared oculography and used time
to perform each tests (1-3) as outcome measure. For eye movement
study, we analysed the fixations, saccades, and blinks.
Results: In normal individuals, mean duration of the King-Devick
Test was shorter using the hand-held test (test-1: 13.5±6.5 s; test-2:
12.9±4.1 s; test-3: 13.3±6.7 s; N=9) than the computer test (test1: 15.9±0.8, P=0.04; test-2: 15.7±0.6 P=0.001; test-3: 16.5±0.7,
P=0.008; N=10). In normals, there was no significant difference in
the time from test-1 to test-3 (P=0.5-0.9), although test-1 was the
easiest test (guiding lines, generous spacing) and the test-3 was the
hardest test (no guiding lines, smallest spacing). Although each test
only had 40 fixation targets (5 numbers per line, 8 lines total), eye
tracking revealed that each subject made 104±5.9 (range 62-132)
fixations, which is more than twice the number needed. The number
of saccades was 161±38 (range 97-466), which is on average more
than twice more fixations. The average saccade amplitudes were
test-1: 4.8±0.1, test-2: 4.9±0.3, test-3 5.0±0.4 deg), with saccade
latencies of test-1: 194.0±24.8 ms, test-2: 197.5±28.1 ms, test-3:
213.6±21.0 and average saccade velocities test-1: 98.7± deg/s, test-2:
99.6±6.6, test-3: 104.8±5.0. The subjects that took the longest time to
perform the task had the most number of saccades, likely because of
backtracking.
Conclusions: We used 500-Hz binocular 2D infrared oculography
to analyze eye movement behaviour during the King-Devick Test.
Although there were 40 fixation targets per test, all subjects made
at least twice as many fixation attempts. Shorter test time correlated
with fewer saccades, blinks, and higher saccade amplitudes. The
King-Devick saccade-based task is a useful test to assess eye
movement abnormality in head trauma and various neuro-ophthalmic
conditions, in order to assess why different subject populations
perform differently.
Commercial Relationships: M Ali Shariati, None; Ming-Hui Sun,
None; Yaping J. Liao, None
Support: Burroughs Wellcome Foundation
Program Number: 2928 Poster Board Number: D0027
Presentation Time: 8:30 AM–10:15 AM
Motion Sharpening of Looming Vertical Bars
Shannon Moore, Glen L. McCormack. Vision Science, New England
College of Optometry, Boston, MA.
Purpose: Our lab previously showed, at ARVO ‘14, that nonfixated
blurred vertical bars moving in stereoscopic depth appear sharper
than when stationary. This sharpening exceeded that of conjugate
lateral motion having the same retinal image velocities. The purpose
of this study was to determine whether nonfixated blurred vertical
bars appearing to loom within a monocular optical flow field would
also be sharpened more than bars appearing to move laterally.
Methods: 15 normally binocular young adults monocularly viewed
four 30 minarc-wide vertical bars drawn on a monitor 40cm from the
eyes. All bars appeared simultaneously for 0.5 sec about a 5 minarc
white fixation spot. Two of the bars (above or below fixation) loomed
toward (or away) from the subject with horizontal velocities of 1.75,
3.5, or 7∆/sec, while the other two bars were static. The edges of the
bars were blurred by cosine luminance profiles, which were fixed at
25 minarc for the moving bars and adjusted by an adaptive staircase
procedure for the static bars to match the blur of the moving bars.
Looming bars underwent horizontal separation, vertical size change,
and vertical position change commensurate with looming. In the
horizontal motion control condition the two moving bars laterally
separated from each other, without vertical size or position change.
In the vertical motion control condition the moving bars grew and
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
moved vertically in a manner commensurate with looming, but
without a horizontal position change.
Results: A mixed ANOVA evaluated the effects of motion type
(looming, horizontal, or vertical), subject, and velocity (1.75, 3.5,
or 7) on sharpening. Motion sharpening increased significantly with
velocity (f=156, p≈0.0), and differed significantly between subjects
(f=4.56, p≈0), like we found previously. At the highest velocity, the
looming bar edges were subjectively sharpened by 13% of their base
blur of 25 minarc. Motion sharpening differed between motion types
(f=20.7, p≈0), but this difference was mostly between the vertical
condition and the other two conditions. Sharpening during looming
was only 3% greater than during lateral motion (insignificant).
Conclusions: While motion sharpening was clearly evident in the
looming and lateral motion conditions, the trivial difference between
them argues that the appearance of motion in depth by way of
looming does not add to motion sharpening.
Commercial Relationships: Shannon Moore, None; Glen L.
McCormack, None
Program Number: 2929 Poster Board Number: D0028
Presentation Time: 8:30 AM–10:15 AM
Induced Audio/Visual Cortical Remapping via Looming Stimulus
Mark H. Myers1, Daniel Albarran1, Ally Dobbins1, Charlotte Joure1,
Aaron Canales2, Gavin Bidelman3. 1Ophthalmology, University
of Tennessee Health Science Center, Memphis, TN; 2Psychology,
University of Memphis, Memphis, TN; 3School of Communication
Sciences & Disorders, University of Memphis, Memphis, TN.
Purpose: Induced audio/visual integration in non-synesthetes will
demonstrate similar intraparietal (IPL) behavior which has been
found to elicit signature neural activity found in as individuals who
have the condition known as synesthesia. The parietal activations
might reflect involvement of a “multisensory nexus” that, via
disinhibition, lead to synesthetic experiences. Measurement of audio/
visual integration will be accomplished via electroencephalography
(EEG) signal neuro-markers.
Methods: Our studies demonstrate Audio/Visual (AV) integration
through the application of looming audio and visual stimuli on nonsynesthetes. Participants were subjected to a combination of looming,
receding or static audio and visual stimuli during EEG recordings.
AV stimuli were presented as audio-looming (AL), visual looming
(VL), or audio-looming/visual looming (ALVL). Audio looms start at
a low intensity and quickly increase by ~10 dB over 1000 ms (AL),
while images would start small and quickly enlarge into the visual
area (VL), or stimuli may occur simultaneously as ALVL. Individuals
were required to rapidly judge whether stimuli was looming or
receding. Behavioral responses to AV stimuli were programmatically
coupled to EEG recordings so that stimuli could be later associated to
cortical responses.
Results: Distributed current source density analysis using low
resolution electromagnetic tomography (LORETA) is applied to the
EEGs of n=4 subjects. Auditory looming (AL) stimuli containing
only auditory cues primarily recruit cortical areas associated with
auditory sensory encoding including Heschl’s Gyrus (HG) in the
superior temporal plane. Similarly, visual-only looms activate
primary visual centers situated in lateral occipital (LO) cortex. In
contrast, looming stimuli combining both auditory and visual cues
(ALVL) engage multimodal area in intraparietal (IPL) cortex. These
preliminary findings indicate that our novel stimulus paradigm
induces cross-modal “hyperbinding” and the integration of AV neural
activity patterns as observed in actual synesthetes.
Conclusions: These preliminary findings demonstrate feasibility
of the proposed stimulus paradigm and perceptual and
neurophysiological correlates of cross-modal “hyperbinding”.
Commercial Relationships: Mark H. Myers, None; Daniel
Albarran, None; Ally Dobbins, None; Charlotte Joure, None;
Aaron Canales, None; Gavin Bidelman, None
334 Amblyopia
Tuesday, May 05, 2015 11:00 AM–12:45 PM
4CD Mile High Blrm Paper Session
Program #/Board # Range: 3190–3196
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Program Number: 3190
Presentation Time: 11:00 AM–11:15 AM
Increased ‘noise’ in V2 neurons of amblyopic monkeys
Bin Zhang1, 2, Xiaofeng Tao2, Janice M. Wensveen2, Earl L. Smith2,
Yuzo M. Chino2. 1College of Optometry, Nova Southeastern
University, Plantation, FL; 2University of Houston, College of
Optometry, Houston, TX.
Purpose: Experiencing early strabismus or chronic monocular
defocus due to anisometropia often causes amblyopia unless treated
early. Besides reduced acuity and contrast sensitivity, a broad range
of more complex spatial and temporal vision deficits have been
reported in amblyopes. Increased neural noise in their visual brain
has been proposed as one of the sources for reduced visual functions
(Levi, 2013). Here we investigated the possible origin of increased
internal noise in non-human primates with anisometropic amblyopia.
Methods: We recorded from multiple nearby neurons in Visual Area
V2 of adult monkeys reared with monocular defocus between 3
weeks and 3 months of age and developed moderate ansiometropic
amblyopia. Stimuli were drifting gratings (3.1 Hz) that were
optimized for orientation, spatial frequency, and size for each neuron
and were presented at low (25%) and high (80%) contrast for 100
times. For individual neurons, the variance of inter-spike intervals
and variance to mean ratio (VMR) of spike counts were calculated.
For multiple neurons recorded at the same site, noise correlation was
computed.
Results: 1) There was no difference in variance of inter-spike interval
among neurons driven by the amblyopic eye, those driven by the
fellow eye, and normal V2 neurons. 2) With low contrast stimuli,
the VMR (trial-to-trial fluctuation) was significantly elevated in V2
neurons driven by both the amblyopic and fellow eyes compared
to that in normal monkeys. With high contrast gratings, there was
no difference. 3) Noise correlation in amblyopic monkeys was
significantly higher than that in normal monkeys at both low and high
contrasts.
Conclusions: Our results suggest that the more variable (noisy)
responses of individual neurons and the elevated noise correlation
in V2 of amblyopic monkeys, combined with abnormal response
dynamics and disorganized subfield structures of V2 neurons, may
affect signal processing down stream, which in turn may limit their
visual performance.
Commercial Relationships: Bin Zhang, None; Xiaofeng Tao,
None; Janice M. Wensveen, None; Earl L. Smith, None; Yuzo M.
Chino, None
Support: EY-008128, EY-003611, P30 EY-007551
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 3191
Presentation Time: 11:15 AM–11:30 AM
Binocular combination in children with deprivation amblyopia
Lisa M. Hamm1, Zidong Chen2, Joanna Black1, Jinrong Li2, Shuan
Dai3, 4, Minbin Yu2, Benjamin Thompson1, 5. 1Optometry and Vision
Science, University of Auckland, Auckland, New Zealand; 2State
Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center,
Sun Yat-sen University, Guangzhou, China; 3Starship Children’s
Hospital, Auckland District Health Board, Auckland, New Zealand;
4
Ophthalmology, University of Auckland, Auckland, New Zealand;
5
Optometry and Vision Science, University of Waterloo, Waterloo,
ON, Canada.
Purpose: Binocular combination is possible in many patients with
strabismic, anisometropic or mixed amblyopia when contrast is
appropriately balanced between the eyes. We tested the hypothesis
that children with deprivation amblyopia, due to a history of early
childhood cataract, are also capable of binocular combination.
Methods: Thirty-six children (mean age 9±2years) with a history
of early bilateral cataract (n=9), early unilateral cataract (n=8),
anisometropic amblyopia (n=9) or normal vision (n=10) were
recruited. Binocular combination was assessed using an established
dichoptic global motion paradigm, whereby high contrast signal
elements are presented to the amblyopic or non-dominant eye
and noise elements are shown to the fellow or dominant eye with
varied contrast. A measurable motion coherence threshold indicates
binocular combination of the signal and noise elements.
Results: Binocular combination could be measured for 7 of 9
bilateral deprivation cases, 5 of 8 unilateral deprivation cases, and
all participants with anisometropic amblyopia or normal vision.
Children with bilateral or unilateral deprivation amblyopia required
significantly larger interocular contrast differences for binocular
combination than children with anisometropic amblyopia or normal
vision (p < 0.05).
Conclusions: It was possible for the majority of children with
deprivation amblyopia to combine information from both eyes when
contrast was appropriately balanced, although large interocular
contrast differences were required. This suggests that treatments
targeting binocular function may be effective in some cases of
deprivation amblyopia.
Commercial Relationships: Lisa M. Hamm, None; Zidong
Chen, None; Joanna Black, None; Jinrong Li, None; Shuan Dai,
None; Minbin Yu, None; Benjamin Thompson, US12528934 (P),
US8006372 B2 (P)
Support: Neurological Foundation Small Project Grant
Program Number: 3192
Presentation Time: 11:30 AM–11:45 AM
Disparity vergence in infantile esotropia reveals a congenital
deficit for disparity sensitivity
Krista R. Kelly1, Joost Felius2, 3, Santoshi Ramachandran2, Blesson
John2, Reed M. Jost1, Eileen E. Birch1, 3. 1Crystal Charity Ball
Pediatric Vision Evaluation Center, Retina Foundation of the
Southwest, Dallas, TX; 2Laboratory for Visual Disorders and Eye
Movements, Retina Foundation of the Southwest, Dallas, TX;
3
Department of Ophthalmology, University of Texas Southwestern
Medical Center, Dallas, TX.
Purpose: Impaired disparity sensitivity (e.g., decreased stereoacuity)
in children with infantile esotropia (ET) is thought to be a result of
prolonged abnormal visual experience during an early critical period
of visuomotor maturation. Even with early treatment, a stereodeficit
persists in children with infantile ET. Thus, it is unclear whether the
stereodeficit is entirely a consequence of abnormal visual experience
or whether, at least in part, the deficit is congenital. Here, we sought
to answer this question by examining disparity vergence in nonamblyopic, orthotropic children with infantile ET who experienced a
short or long duration of constant misalignment.
Methods: We tested three age-matched groups of children (7.8±2.8
y); 15 controls with a history of normal visual development,
10 infantile ET with a short duration (≤3 months) of constant
misalignment, and 8 infantile ET with a long duration (>3 months) of
constant misalignment. Disparity vergence was recorded using a 500
Hz remote-video binocular eye tracker (EyeLink 1000; SR Research)
following binocular calibration. The child initially fixated on an LED
located on midline at 80 cm, which was extinguished and replaced by
an LED on midline at 30 cm, requiring a vergence response. A total
of 10 vergence responses were recorded and at least 3 artifact-free
responses were required for analyses. Mean response gain (vergence
angle/vergence demand) was calculated.
Results: Compared with controls, short and long duration of infantile
ET resulted in a 22% and 54% decrease in disparity vergence gain,
respectively (p ≤ 0.009). Even those with 0 months duration of
constant misalignment (i.e., infantile accommodative intermittent
ET) exhibited a 20% decrease in vergence (p = 0.012) compared
with controls. Further, long duration of infantile ET resulted in a
decrease of 41% compared with short duration (p = 0.037). While
14/15 controls showed smooth disparity vergence, 5/10 short duration
ET and 7/8 long duration ET children exhibited pure saccades, a
combination of saccades and vergence, or vergence combined with
saccadic oscillations or nystagmus.
Conclusions: Impaired disparity vergence following zero and short
duration of constant misalignment indicates that a congenital deficit
in disparity sensitivity is present in children with infantile ET,
which can be exacerbated by prolonged abnormal binocular visual
experience.
Commercial Relationships: Krista R. Kelly, None; Joost Felius,
None; Santoshi Ramachandran, None; Blesson John, None; Reed
M. Jost, None; Eileen E. Birch, None
Support: National Eye Institute EY022313
Program Number: 3193
Presentation Time: 11:45 AM–12:00 PM
Disconjugacy of eye alignment is greater with near fixation
during binocular viewing in amblyopia
Howard S. Ying, Vivian Xu, Robert B. Geary, Boris I. Gramatikov,
David L. Guyton, Kristina Irsch. Ophthalmology, Johns Hopkins
University, Baltimore, MD.
Purpose: To determine whether ocular disconjugacy in amblyopic
subjects is dependent on viewing condition.
Methods: Binocular eye movements were recorded at 500 Hz using
the EyeLink 1000 eye tracker (SR Research Ltd., Ontario, Canada).
Twenty subjects (nine normal and eleven amblyopic; age: 8-45 years)
were asked to fixate on a blue cross subtending 0.5° at a near distance
of 57 cm or at a far distance of 4 m for 20-second epochs of binocular
or monocular viewing. Disconjugacy of eye alignment was estimated
by 1) the area of the 68% bivariate contour ellipse (BCEA) for the
difference between right and left eye positions, 2) the percentage
of fixation time within a 0.1°x 0.1° range, and 3) microsaccade
characteristics. Mean ± standard error of the mean were calculate,
log(BCEA) was used to normalize the distributions, and significance
testing was performed with the Student’s t-test.
Results: Normal subjects during binocular viewing showed a 68%
BCEA of 0.75 deg2 ± 0.09 deg2 with near fixation and 0.81 deg2 ± 0.14
deg2 with far fixation (P=0.69) while subjects with amblyopia during
binocular viewing showed a 68% BCEA of 5.60 deg2 ± 0.78 deg2 with
near fixation and 3.08 deg2 ± 0.31 deg2 with far fixation (P=0.01).
Mean percentage of conjugate fixation time for normal subjects
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
was 99.5% ± 0.3% for near fixation and 99.6% ± 0.1 for far fixation
(P=0.66), and for amblyopic subjects was 98.4% ± 0.2% for near
fixation and 99.2% ± 0.1% for far fixation (P=0.02). Disconjugacy
was associated with more microsaccades and more square wave jerks.
Monocular viewing trials showed more disconjugacy than binocular
trials for normal subjects but not for amblyopic subjects.
Conclusions: Disconjugacy increases with near fixation for
amblyopic subjects during binocular viewing due to increased slow
drift and microsaccades. Further research is required to determine
which metrics have greater diagnostic utility in amblyopia.
Commercial Relationships: Howard S. Ying, Johns Hopkins
University (P); Vivian Xu, None; Robert B. Geary, Johns Hopkins
University (P); Boris I. Gramatikov, Johns Hopkins University (P);
David L. Guyton, Johns Hopkins University (P); Kristina Irsch,
Johns Hopkins University (P)
Support: NIH Grant EY 19347, Research to Prevent Blindness
Disney Award, William Cross Foundation
Program Number: 3194
Presentation Time: 12:00 PM–12:15 PM
Fixational Eye Movements in Amblyopia: The Effect of Reduced
Visual Feedback
Joost Felius1, 2, Santoshi Ramachandran1, Reed M. Jost1, Krista
R. Kelly1, Eileen E. Birch1, 2, Angie De La Cruz1, Blesson John1.
1
Retina Foundation of the Southwest, Dallas, TX; 2Ophthalmology,
University of Texas Southwestern Medical Center, Dallas, TX.
Purpose: In attempts to better understand the effects of visual
feedback on fixation stability in amblyopes, previous studies have
included an ‘open loop’ test condition, in which the eye movements
of the non-viewing (covered) eye were assessed. But interpretation
of the results has been hampered by the incomplete knowledge of the
link between eye movements of the two eyes. Here we study fixation
stability in a ‘pseudo-open loop’ condition with reduced visual
feedback to the viewing eye(s).
Methods: Seventeen children with amblyopia (age 5-15 years;
visual acuity 0.2-1.2 logMAR) and 10 age-similar normal controls
participated. Fixational eye movements were recorded at 500
Hz under monocular (amblyopic eye) and binocular viewing
conditions using two fixation targets: a small 0.3°-diameter dot and
a 2-dimensional Gaussian profile (σ=1.25°), the latter appearing
as a blurred disk providing only minimal visual feedback. Fixation
stability was studied in terms of the bivariate contour ellipse area
(BCEA) and the mean amplitude and rate of microsaccades.
Results: In controls, fixation stability was best when binocularly
viewing the dot (BCEA, -0.52±0.71 log deg2) and poorest when
monocularly viewing the Gaussian profile (+0.60±1.09 log deg2).
Similarly, in the amblyopic children, fixation stability was best when
binocularly viewing the dot (BCEA, -0.17±0.53 log deg2) and poorest
when viewing the Gaussian profile with only the amblyopic eye
(+0.44±0.47 log deg2). However, the deterioration of fixation stability
under reduced visual feedback was smallest in the amblyopes when
viewing with the amblyopic eye. Group differences in BCEA were
larger when viewing the dot than when viewing the Gaussian profile
(2-way ANOVA, P<0.03). For both controls and amblyopes, the
deterioration of fixation stability under reduced visual feedback was
associated with increases in amplitude but not rate of microsaccades
(P<0.016).
Conclusions: Amblyopes showed a smaller-than-normal decrease in
fixation stability when visual feedback was reduced in the ‘pseudoopen loop’ condition, consistent with a weakened input of visual
feedback into the fixation control mechanism. This effect may hold
promise as an objective ocular motor measure for the detection of
amblyopia.
Commercial Relationships: Joost Felius, None; Santoshi
Ramachandran, None; Reed M. Jost, None; Krista R. Kelly,
None; Eileen E. Birch, None; Angie De La Cruz, None; Blesson
John, None
Support: Orix Foundation; NIH EY022313
Program Number: 3195
Presentation Time: 12:15 PM–12:30 PM
Dichoptic Movie Treatment of Childhood Amblyopia
Simone L. Li1, Alexandre Reynaud2, Robert F. Hess2, Yi-Zhong
Wang1, 3, Reed M. Jost1, Sarah E. Morale1, Angie De La Cruz1,
Lori Dao4, David Stager4, Eileen E. Birch1, 3. 1Retina Foundation
of the Southwest, Dallas, TX; 2Ophthalmology, McGill University,
Montréal, QC, Canada; 3Ophthalmology, UT Southwestern Medical
Center, Dallas, TX; 4Pediatric Ophthalmology & Adult Strabismus,
Plano, TX.
Purpose: Contrast-balanced dichoptic experience with perceptuallearning tasks, games, or both has been shown to improve visual
acuity in amblyopia. We previously demonstrated that repeated
binocular experience via at-home binocular iPad game play with
reduced fellow-eye contrast was effective in treating childhood
amblyopia1,2 and that visual acuity was maintained for ≥12 months3.
However, these tasks are intensive and repetitive and up to 40%
of patients are noncompliant.1,2,4 Here we investigated the efficacy
of a potentially more engaging movie method to provide contrastbalanced binocular experience via complementary dichoptic
stimulation.
Methods: Seven amblyopic children (4-10y; 0.5-1.2 logMAR or
20/63-20/320) were enrolled in a prospective cohort study to watch
3 dichoptic movies per week for 2 weeks on a passive 3D display.
Dichoptic versions of 18 popular animated feature films were created.
A patterned image mask of irregularly shaped blobs was multiplied
with the movie images seen by the amblyopic eye and an inverse
pattern mask was multiplied with the images seen by the fellow eye.
Fellow-eye contrast was initially set for each amblyopic child at a
reduced level that allowed binocular vision and was incremented
by 10% at each visit. At the baseline and 2-week outcome visits,
BCVA, random dot stereoacuity, interocular suppression, and fixation
stability were measured. None of the children had any concurrent
amblyopia treatment during this study.
Results: After watching 6 dichoptic movies during a two-week
period (9.3±0.8 hours), mean (±SE) amblyopic eye BCVA improved
from 0.71±0.10 logMAR at baseline to 0.54±0.10 logMAR (p=
0.006); i.e. 1.7 lines. Three children with 0.5 logMAR baseline
BCVA improved 0.1 logMAR (1 line); three children with 0.7-0.8
logMAR baseline BCVA improved 0.2-0.4 logMAR (2-4 lines), and
one child with 1.2 logMAR baseline BCVA improved 0.1 logMAR
(1 line). Fellow-eye BCVA did not change significantly during the
study (p=0.19). No significant change in random dot stereoacuity,
interocular suppression, or fixation stability was found.
Conclusions: Repeated contrast-balanced binocular visual experience
significantly improved amblyopic-eye visual acuity. Contrastbalanced dichoptic feature films may result in better compliance
than repetitive perceptual-learning tasks or games. 1. Li et al Eye
2014; 28:1246-53. 2. Birch et al J AAPOS in press. 3. Li et al JAMA
Ophthal in press.
4. Levi et al JOV 2014; 14:959
Commercial Relationships: Simone L. Li, None; Alexandre
Reynaud, McGill University (P); Robert F. Hess, McGill University
(P); Yi-Zhong Wang, None; Reed M. Jost, None; Sarah E. Morale,
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
None; Angie De La Cruz, None; Lori Dao, None; David Stager,
None; Eileen E. Birch, None
Support: NEI Grant EY022313
Program Number: 3196
Presentation Time: 12:30 PM–12:45 PM
Evaluation of a Novel Digital Infant Acuity Test
Laura A. Butler1, Esther Misanjo2, Duncan Middleton3, Iain
Livingstone4, Petros Kayange2. 1Care of the Elderly, NHS Lothian,
Edinburgh, United Kingdom; 2Ophthalmology, Queen Elizabeth
Central Hospital, Blantyre, Malawi; 3Clinical Physics and
Bioengineering, NHS Greater Glasgow and Clyde, Glasgow, United
Kingdom; 4Ophthalmology, NHS Greater Glasgow and Clyde,
Glasgow, United Kingdom.
Purpose: The testing of infant acuity is vital in treatment and
prevention of amblyopia. Current card-based clinical standards
encounter a number of problems including expense, wear and tear
issues, portability and child engagement; digital devices provide the
potential to resolve many of these limitations but have not yet been
validated. The purpose of this study was to assess the validity of a
novel digital tablet-based touchscreen high-frequency grating acuity
test in Blantyre, Malawi.
Methods: Children aged 6 to 60 months who presented to the Eye
Unit were eligible. Acuity was measured using “gold standard”
Keeler cards and the Peekaboo digital test (see Figure 1) for right,
left, and both eyes. Following a minimum interval of 20 minutes,
patients were re-tested by the same assessor. In addition to age and
LogMAR acuity, child engagement was recorded using a compliance
score (CS) of 0-2 (0 = no engagement, 2 = perfect compliance).
Statistical methods described by Bland and Altman were used to
compare the two modalities.
Results: A total of 58 patients were recruited with mean age of 33
months. The average difference in acuity between modalities was
-0.1 (95% lower and upper LoA -0.69, +0.49 respectively). Subset
analysis of children with CS of 2 for all tests (see Figure 2) revealed
a difference of +0.02 (95 % LoA of -0.33 and +0.36 respectively).
CS averaged 1.5 for the digital test, compared to 1.3 with Keeler
(p<0.001). On test-retest analysis, the digital test showed an average
difference of +0.007 (95% LoA -0.385 to 0.370) between first and
second tests compared to Keeler which demonstrated a difference of
-0.04 (95% LoA -0.683 to 0.674). The digital test demonstrated 95%
repeatability coefficient of 0.29, compared with 0.38 for Keeler.
Conclusions: The present study demonstrates good levels of
agreement between digital and card-based methods, with 95% LoA
within appropriate limits for the young test population. The digital
test outperformed Keeler in terms of child engagement and reliability.
Digital high-frequency grating acuity testing represents a promising
advance for assessing vision in the very young. Additionally, due to
it’s lower cost compared to current modalities, it has the potential for
use in low to middle income countires, such as Malawi.
Figure 1A. Keeler Acuity Test (Keeler ltd). 1B. Peekaboo Digital
Acuity test on iPad 3 (Apple inc).
Bland Altman plot for Keeler vs Digital - subset of children with CS
of 2 for all tests
Commercial Relationships: Laura A. Butler, None; Esther
Misanjo, None; Duncan Middleton, None; Iain Livingstone, None;
Petros Kayange, None
Support: Funding from Fiona’s Eye Fund - registered UK charity
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
381 Leber’s Hereditary Optic Neuropathy / Clinical testing
Tuesday, May 05, 2015 3:45 PM–5:30 PM
Exhibit Hall Poster Session
Program #/Board # Range: 3856–3886/C0261–C0291
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Contributing Section(s): Biochemistry/Molecular Biology,
Multidisciplinary Ophthalmic Imaging, Retina, Visual Psychophysics/
Physiological Optics
Program Number: 3856 Poster Board Number: C0261
Presentation Time: 3:45 PM–5:30 PM
Clinically-Significant Cardiac Pathology in Leber’s Hereditary
Optic Neuropathy
Starleen E. Frousiakis6, Rustum Karanjia2, Jeffrey S. Tran1,
Andrew E. Pouw1, Chiara La Morgia4, Milton Moraes3, Solange
R. Salomao5, Peter Quiros2, Valerio Carelli4, Alfredo A. Sadun2.
1
Ophthalmology, University of Southern California, Woodland
Hills, CA; 2Ophthalmology, UCLA, Los Angeles, CA; 3Instituto de
Olhos de Colatina, Colatina, Brazil; 4Department of Ophthalmology,
University of Bologna, Bologna, Italy; 5Federal University of Sao
Paulo, Sao Paulo, Brazil; 6Ophthalmology, Univeristy of Southern
California, Los Angeles, CA.
Purpose: To determine the association of clinically-significant
cardiac pathology with status as a carrier or affected subject, and to
compare previous findings on cardiac conduction in affected patients
with Leber’s hereditary optic neuropathy (LHON), 11778 mutation,
to a distinct pedigree.
Methods: Cardiac pathology was defined by past history of stroke,
myocardial infarction, angina, and/or palpitations. Subjects were
compared based on LHON status: control, carrier, or affected. A
logistic regression model was constructed, controlling for age and
body mass index (BMI). Data from a previously published cohort of
affected Brazilian patients (n1=23) and newly-acquired values from a
distinct Italian cohort (n2=21) were compared to a database of healthy
controls (n2=87). Each population underwent ECG testing, performed
by a cardiologist, with measurement of PR interval and QTc duration.
An unpaired student’s t-test was performed to determine if there was
a difference between affected populations and controls.
Results: The final regression model indicates that LHON status is
not correlated with an increased prevalence of cardiac pathology in
the sample population. Age is a significant predictor, but interaction
between age and status did not yield a significant difference between
groups. BMI was not found to be a significant predictor of cardiac
pathology. Mean PR intervals and standard deviations in the Italian
pedigree, Brazilian pedigree and control population were 140.6±20.6,
127.2±26.1 and 136.9±9.1, respectively. There was no significant
difference detected in mean PR interval between the Italian pedigree
and healthy controls, thereby validating the previously-published
findings in the Brazilian population. However, this study similarly
demonstrated a subgroup of patients within the Italian pedigree
who had a shortened PR interval (n=2). There was no significant
difference in QTc duration between affected and control populations
in either pedigree.
Conclusions: Carrier and affected populations of LHON do not
demonstrate increased prevalence of clinically-significant cardiac
pathology. This study validated the previously published findings
of a non-significant difference in PR interval and QTc duration in
affected patients with LHON and controls. A subgroup of subjects
with shortened cardiac conduction may be indicative of patients at
increased risk for conduction defects.
Commercial Relationships: Starleen E. Frousiakis, None;
Rustum Karanjia, None; Jeffrey S. Tran, None; Andrew E. Pouw,
None; Chiara La Morgia, None; Milton Moraes, None; Solange
R. Salomao, None; Peter Quiros, None; Valerio Carelli, None;
Alfredo A. Sadun, None
Program Number: 3857 Poster Board Number: C0262
Presentation Time: 3:45 PM–5:30 PM
Phenotypic Variability in a Pedigree with Leber Hereditary Optic
Neuropathy (LHON)
Sherry J. Bass1, Daniel Epshtein1, Sanjeev Nath2, Jerome Sherman1,
2 1
. Clinical Sciences, SUNY College of Optometry, New York, NY;
2
The Eye Institute, New York, NY.
Purpose: To report typical and atypical serial findings in three
members of a LHON pedigree with an mt3460 mutation
Methods: Three siblings born of a mother with acute onset LHON
at age 20, an mt3460 genotype and 20/1000 VA were examined and
followed over a 5 year period. The 300-year pedigree was noted for a
history of profound vision loss, surprisingly preferential to females.
The youngest sibling studied was a 7 year-old male with an initial
best-corrected visual acuity (BCVA) of 20/20 OD and 20/25 OS.
The second sibling studied was a 14 year-old female with BCVA
20/20 OD/OS. The third sibling was a 16 year-old male with BCVA
20/20 OD/OS. In addition to visual acuity, testing included fundus
examination with fundus photography, OCT of the retinal nerve fiber
layer (RNFL) and ganglion cell analysis (GCA).
Results: The 7 year-old male had an atypical finding of pale discs
OU. RNFL Analysis (Zeiss Cirrus) revealed RNFL loss superiorly,
temporally, and inferiorly in both eyes. GCA revealed a profound
loss of ganglion cells in the macula. Examination of the 14 year-old
female revealed a hyperemic disc with peripapillary telangiectatic
microangiopathy. The RNFL was thickened nasally in both eyes.
GCA was statistically normal. Examination of the 16 year-old
brother revealed mild peripapillary telangiectatic microangiopathy in
both eyes. The right eye’s RNFL was normal but superior temporal
thinning was seen in the left eye. Diffuse GCA thinning was seen
in both eyes with denser loss inferiorly OD and temporally OS.
Examination at 5 year follow-up revealed no change in any of
the above findings in any of the two siblings with peripapillary
telangiectatic microangiopathy. However, in the youngest sibling
with pale discs, there was a one line reduction in visual acuity in both
eyes but no additional changes in the examination findings.
Conclusions: The rare presentation of early onset progressive LHON
has only been reported in mt17778 pedigrees. This pedigree, with a
mutation in the mt3460 locus, presents with characteristic findings of
both typical LHON and rare atypical early-onset progressive LHON.
Fundus photography, GCA, and RNFL analysis reveal varying stages
of optic nerve appearance and optic neuropathy. This pedigree also
reveals the existence of atypical early onset progressive LHON with
good vision and an mt3460 mutation previously (to the authors’ best
knowledge) unreported in the world’s literature.
Commercial Relationships: Sherry J. Bass, None; Daniel
Epshtein, None; Sanjeev Nath, None; Jerome Sherman, None
Program Number: 3858 Poster Board Number: C0263
Presentation Time: 3:45 PM–5:30 PM
Leber’s hereditary Optic Neuropathy: cellular pathophysiology,
potential animal model, and cell-based drug screens for potential
therapeutics
Gino Cortopassi, Alfred K. Yu, Lanying Song, Karl Murray.
Molecular Biosciences, University of California, Davis, Davis, CA.
Purpose: Leber’s hereditary Optic Neuropathy (LHON) is
an inherited mitochondrial disease, resulting from mutations
in mitochondrial complex 1, which cause degeneration of
retinal ganglion cells, for which there is no cure. We analyzed
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
pathomechanism in LHON cells, implicating the mitochondrial
complex I defect, and ATF4 and CHOP and inflammatory
markers. We show the ndufs4 complex 1 knockout mouse
has significant depletion of RGC function, and RGC loss,
coincident with a strong rise in multiple inflammatory markers.
We have designed and improved cell-based screening assays
of 6 mitochondrial functions in cybrids bearing the LHON
mutation, and screened through 1600 FDA-approved drugs
to identify those which rescue LHON-specific defects. The
studies of pathomechanism support a model of LHON in which
primary mutations drive complex I structural changes that cause an
inflammatory response and RGC functional loss and death, and the
drug screening studies identify potential therapeutics.
Methods: Microarrays were carried out as published previously.
RNASeq and MicroElectrode Array (MEA) analysis of retinas of
Ndufs4 KO and wild type controls were carried out using standard
procedures.
Results: Cell-based pathomechanism. Results include the
mitochondrial complex-1 dependent induction of ATF4 and CHOP
and potential inflammatory markers. LHON animal model. The
ndufs4 KO mouse has loss of RGC function and RGC cell death as in
human LHON, and a substantial induction of inflammatory markers
in the retina, coincident with RGC functional loss by MEA. Drug
based screening. Partial poisoning of complex I uncovers a LHON
mutation-specific defect in complex I-driven ATP synthesis that can
be screened for drugs that protect from this defect. Such drugs fall
in particular structural and functional categories. Drug secondaries
and mechanistic understanding. Secondary screening is in progress
for hit confirmation, and mechanism of protective effect is being
generated for particular hits. Testing in animal model of LHON.
Top hits are entering animal testing, and preliminary results are likely
to be available by the meeting time.
Conclusions: We have identified a mechanism of LHON, an animal
model of LHON, and are screening therapeutics of potential benefit
in LHON cells.
Commercial Relationships: Gino Cortopassi, None; Alfred K. Yu,
None; Lanying Song, None; Karl Murray, None
Support: R01 EY012245
Program Number: 3859 Poster Board Number: C0264
Presentation Time: 3:45 PM–5:30 PM
Evaluation of visual field metrics in patients with central
scotomas from LHON
Alexander F. Chen1, Amitha Ganti1, Youning Zhang1, Tiffany
Hwang1, Adriana Berezovsky2, Milton Moraes2, 3, Jeffrey S.
Tran1, Tana Wagschal5, Rustum Karanjia4, Alfredo A. Sadun4.
1
Ophthalmology, University of Southern California, Los Angeles,
CA; 2Ophthalmology, Universidade Federal de Sao Paulo, Sao Paulo,
Brazil; 3Centro Universitario do Espirito Santo, Colatina, Brazil;
4
Doheny Eye Institute, Pasadena, CA; 5Visual Field Reading Center,
University of Iowa, Coralville, IA.
Purpose: Patients with large and dense central scotomas may be
unable to reliably complete Stimulus size III (Stim III) Humphrey
Visual Fields (HVF). These patients, however, do considerably better
with Stimulus size V (Stim V) HVF. In Leber’s Hereditary Optic
Neuropathy (LHON) the reliability of the HVF varies over the course
of the disease. The purpose of this study was to determine if Stim
III and Stim V mean deviation (MD) calculations are equivalent in
patients with central scotomas from LHON.
Methods: 10 patients with LHON were administered Stim III and
Stim V HVF tests on the same day during multiple patient visits. Stim
III MD values were obtained from the HVF algorithm. In addition,
separate Stim III and Stim V MD values were obtained from an
investigative algorithm (IA). This IA, developed by the University of
Iowa Visual Field Reading Center, was used to derive patients’ MD
from Stim III and Stim V HVF raw numerical data. The MD values
from the HVF and IA were compared using a Pearson’s productmoment correlation coefficient.
Results: A total of 72 observations, 10 patients and 18 eyes were
analyzed. Stim III HVF and IA: r^2=0.99, HVF mean MD=-26.1 with
standard deviation (STD)=+/-6.72. IA mean MD=24.1 with STD=+/6.30. Mean absolute difference between HVF and IA =1.98 with
STD=+/-0.769. IA Stim III MD and Stim V MD: r^2=0.415, Stim
V mean MD=-21.2 with STD=+/-5.52. Mean absolute difference
between IA Stim III and Stim V MD=1.98 with STD=+/-2.97.
Conclusions: There was near perfect correlation of Stim III MD
between HVF and IA, validating the algorithm. MD values for Stim
III and Stim V, however, were not interchangeable. This may reflect
the variability that comes from visualizing the smaller stimulus in
subjects with a dense central scotoma.
Commercial Relationships: Alexander F. Chen, None; Amitha
Ganti, None; Youning Zhang, None; Tiffany Hwang, None;
Adriana Berezovsky, None; Milton Moraes, None; Jeffrey S. Tran,
None; Tana Wagschal, None; Rustum Karanjia, None; Alfredo A.
Sadun, Edison Pharmaceuticals (F)
Program Number: 3860 Poster Board Number: C0265
Presentation Time: 3:45 PM–5:30 PM
Functional Visual Outcome of 1st vs 2nd Affected Eye in Treated
LHON Patients at 1 Year
Michael Ammar1, Jasdeep S. Chahal1, Amitha Ganti1, Jeffrey S.
Tran1, Edward R. Chu3, Alexander F. Chen1, Tiffany Hwang1, Rustum
Karanjia2, 3, Alfredo A. Sadun2, 3. 1USC Eye Institute, University of
Southern California, Los Angeles, CA; 2Ophthalmology, University
of California at Los Angeles, Los Angeles, CA; 3Doheny Eye
Institute, Los Angeles, CA.
Purpose: Leber’s Hereditary Optic Neuropathy (LHON) is
a mitochondrial optic neuropathy with no definitive therapy.
Involvement of the first eye is usually followed by the second eye
within a few months. Thus, the second eye is exposed to systemic
treatment, such as quinone therapy, earlier relative to its onset. We
carried out a retrospective chart review to test our hypothesis that
functional visual outcome is better in the 2nd affected eye at 1 year in
treated LHON patients.
Methods: Charts from 2009 to 2014 were analyzed at a university
affiliated eye institute. Patients were diagnosed with LHON, and
were seen at 1 year ± 2 months after conversion for the 2nd eye. 20
patients were identified and all were given quinone therapy for the
duration of the year. 14 began treatment after both eyes were affected
(hence earlier for 2nd eye) and 6 began after one eye was affected
(hence before visual loss in the 2nd eye). Average time to treatment
after involvement of the 1st eye was 172 days. LogMAR visual acuity
(VA), retinal nerve fiber layer (RNFL) thickness, and mean deviation
(MD) were recorded for 1st and 2nd eyes affected. A two-tailed
Student’s t-test was used for statistical analysis.
Results: At 1 year in the 1st affected eye, patients treated after both
eyes were affected had an average VA of 1.73 ± 1.67, an average
MD of -21.44 ± 7.39, and an average RNFL thickness of 64.75 ±
13.25. In the 2nd affected eye, they had an average VA of 1.78 ± 1.77,
an average MD of -15.82 ± 11.93, and an average RNFL thickness
of 66.13 ± 10.97. At 1 year in patients treated after both eyes were
affected, P values for the 1st vs 2nd affected eye were 0.4546 for VA,
0.1768 for MD, and 0.5342 for RNFL thickness. At 1 year in the 1st
affected eye, patients treated between affected eyes had an average
VA of 2.00 ± 2.08, an average MD of -29.08 ± 3.17, and an average
RNFL thickness of 65.60 ± 11.01. In the 2nd affected eye, they had an
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
average VA of 1.93 ± 2.10, an average MD of -24.22 ± 4.99, and an
average RNFL thickness of 60.20 ± 9.73. At 1 year in patients treated
between affected eyes, P values for the 1st vs 2nd affected eye were
0.1620 for VA, 0.1556 for MD, and 0.1540 for RNFL thickness.
Conclusions: In this LHON cohort, there was a trend but no
statistically significant difference in visual outcome between the 1st
and 2nd affected eye at 1 year. Hence, the timing of quinone therapy
does not appear to be critical.
Commercial Relationships: Michael Ammar, None; Jasdeep
S. Chahal, None; Amitha Ganti, None; Jeffrey S. Tran, None;
Edward R. Chu, None; Alexander F. Chen, None; Tiffany Hwang,
None; Rustum Karanjia, None; Alfredo A. Sadun, None
Program Number: 3861 Poster Board Number: C0266
Presentation Time: 3:45 PM–5:30 PM
Mitochondria haplogroups in patients with dominant optic
atrophy
Isao Nakata, Eric D. Gaier, Daniel Navarro-Gomez, John S.
Borchert, Xiaowu Gai, Louis R. Pasquale, Simmons Lessell, Dean
M. Cestari, Joseph F. Rizzo, Janey L. Wiggs. Ophthalmology,
Massachusetts Eye and Ear Infirmary, Boston, MA.
Purpose: The most common inherited optic neuropathies are
dominant optic atrophy (DOA) caused by mutations in OPA1 and
Leber hereditary optic neuropathy (LHON) caused by mutations in
mitochondrial DNA (mtDNA). Previous studies have suggested that
background mtDNA haplogroups may affect LHON pathogenicity
and expressivity, however, the role of mtDNA halogroups in DOA
remains unexplored. This study aims to identify mtDNA haplogroups
in OPA1-related optic atrophy patients and to investigate the impact
of the haplogroups on the clinical phenotype.
Methods: Fifty-nine patients with the clinical diagnosis of primary
optic atrophy were studied. Genomic DNA was evaluated by next
generation sequencing using the Genetic Eye Disease (GEDi)
diagnostic panel that covers 234 genes (including OPA1) as
well as the entire mitochondrial genome. Patients with apparent
homozygosity based on consecutive single nucleotide polymorphisms
were also evaluated for copy number variation (CNV) using
Multiplex Ligation-dependent Probe Amplification (MLPA)
analysis. The mitochondrial haplogroup was determined using our
custom halplogroup-defining tool Phy-Mer (Navarro-Gomez et al.,
submitted). The difference in clinical phenotype (both ocular and
nonocular) among mtDNA haplogroups was tested with the ANOVA
test for continuous data and with the chi-square test for categorical
data.
Results: In the 59 optic atrophy cases, mtDNA haplogroup analysis
identified 19 cases (32.2%) with haplogroup H, 10 cases (16.9%)
with haplogroup U, and 8 cases (13.6%) with haplogroup J. Next
generation sequencing and CNV analysis identified 21 patients
(35.6%) with OPA1 disease-causing mutations and one patient (1.7%)
with a primary LHON mutation (m.11778G>A). In the overall group
(both with and without OPA1 mutations), significant differences
in age of onset, visual acuity, and visual field among haplogroups
was not observed (P > 0.05) although extra-ophthalmological
abnormalities such as hearing loss and peripheral neuropathy
tended to be more frequent in haplogroup J (42.9%) compared
with haplogroups U/H (16.0%, P = 0.157). In the cases with OPA1
mutations (n = 21), we found significantly more extra-ocular
abnormalities in haplogroup J cases (75.0%) compared to haplogroup
U/H cases (0.0%, P = 0.0140).
Conclusions: This study showed a potential association between
mtDNA haplogroup and extra-ocular findings in DOA with OPA1
mutation.
Commercial Relationships: Isao Nakata, None; Eric D. Gaier,
None; Daniel Navarro-Gomez, None; John S. Borchert, None;
Xiaowu Gai, None; Louis R. Pasquale, None; Simmons Lessell,
None; Dean M. Cestari, None; Joseph F. Rizzo, None; Janey L.
Wiggs, None
Support: JSPS Postdoctoral Fellowships for Research Abroad (IN),
Alcon Research Institute Award (JLW)
Program Number: 3862 Poster Board Number: C0267
Presentation Time: 3:45 PM–5:30 PM
Improvements on a Method for Recognizing Colorblind
Malingering
Andrew E. Pouw1, Rustum Karanjia2, Alfredo A. Sadun2. 1Keck
School of Medicine, University of Southern California, Los Angeles,
CA; 2Ophthalmology, Doheny Eye Institute, University of California
Los Angeles, Los Angeles, CA.
Purpose: Standard tests of colorblindness screen for organic disease.
We have developed a method that attempts to recognize malingerers
of colorblindness. The purpose of this study is to validate this test in a
sample population.
Methods: An online survey was distributed to 84 self-reported and
verified colorblind participants and 131 participants instructed to
simulate colorblind malingering. The survey contained three sets of
twelve color-adjusted versions of the standard Ishihara color plates,
as well as one set of twelve unmodified plates. Participants were
asked to identify numbers on these 48 plates. Two tests were then
created, each using six unique plates. A “balanced test” emphasizing
both sensitivity and specificity was assembled by prioritizing test
plates that colorblind participants most often correctly identified, as
well as those test plates which malingering simulators most often
incorrectly identified. A second set of six test plates comprised the
“specific test,” which maximized test specificity. This was assembled
by prioritizing only those plates that colorblind participants most
often correctly identified. Statistical measures of both the “balanced
test” and “specific test” (sensitivity, specificity, and Youden indexes)
were assessed at each possible cut-off threshold, and a receiver
operating characteristic (ROC) function with its area under the curve
(AUC) charted.
Results: For the “balanced test,” colorblind and colorblind simulating
participants had a difference of means of 60.1% (CI: 53.6% to
66.5%). Statistical measures showed an optimal cut-off of at least
1 missed “balanced test” plate to recognize a colorblind malingerer
(Youden index: 0.81, sensitivity: 88.6%, specificity: 92.9%), with
an AUC of the ROC of 0.93. For the “specific test,” colorblind and
colorblind simulating participants had a difference of means of
41.6% (CI: 34.8% to 48.4%). Statistical measures showed a cut-off
of at least 2 missed “specific test” plates to identify a colorblind
malingerer with 100% specificity (sensitivity 51.9%, Youden index
0.52, AUC of 0.85).
Conclusions: Our method for recognizing colorblind malingering
demonstrates a high degree of reliability in a large population, and
can be used to both screen for colorblind malingerers and to identify
them with 100% specificity.
Commercial Relationships: Andrew E. Pouw, None; Rustum
Karanjia, None; Alfredo A. Sadun, None
Program Number: 3863 Poster Board Number: C0268
Presentation Time: 3:45 PM–5:30 PM
Clinical Value of Electrophysiology in Determining the Diagnosis
of Visual Dysfunction in Neuro-Ophthalmology Patients
GH Yap1, LY Chen2, R Png2, Loo JL2, Tow S2, Mathur Ranjana2, Chia
A2. 1Singapore General Hospital, Singapore, Singapore; 2Singapore
National Eye Center, Singapore, Singapore.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Purpose: Neuro-ophthalmologists often refer patients for
electrophysiology to distinguish between retinal and post-retinal
pathology, and to aid in diagnosis. We performed a retrospective
review to assess clinical value of visual electrophysiology in
identifying causes of visual dysfunction in patients referred from
neuro-ophthalmology clinics.
Methods: A retrospective review of 410 subjects (0.3 – 88 years,
mean 43.6 +/- SD 20.0) referred for visual electrophysiology from
various neuro-ophthalmologists between 2009-2013 was performed.
Most underwent pattern, full-field and multifocal electroretinography
and pattern visual evoked potential (VEP) tests. Flash and multifocal
VEP were included where indicated. Main outcome measures were
the site of pathology and sensitivities for each test.
Results: 158 were referred for poor vision for investigation, 102
for unexplained visual field defects, 97 for miscellaneous visual
symptoms and 53 for other reasons. Most subjects referred for
poor vision for investigation had electrophysiology findings of
retinopathy (37%) or post-retinal pathology (34%), and those with
vision poorer than 6/24 more likely having abnormal findings (86%
vs 62%, p=0.0020). Among those with unexplained visual field
defects, findings of retinopathy, post-retinal pathology and normality
were noted in 31%, 24% and 28%, respectively. Most subjects with
miscellaneous visual symptoms had normal findings (69%). Among
the tests, multifocal ERG was most sensitive for retinopathy (96%)
and maculopathy (95%) and pattern VEP was most sensitive for postretinal pathology (94%). An indeterminate result was noted in 9%.
Conclusions: Electrophysiology was effective in allowing
differentiation between retinopathy, optic neuropathy and
electrophysiologic normality in 91% of subjects. Pre-testing
provisional diagnoses of retinopathy and post-retinal pathology were
revised in 30% and 42% respectively as a result of electrophysiologic
testing. A clear understanding of the characteristics of each test used
in correlation with the clinical picture and interpretation of all results
in totality are important in localising the site of pathology.
Commercial Relationships: GH Yap, None; LY Chen, None; R
Png, None; Loo JL, None; Tow S, None; Mathur Ranjana, None;
Chia A, None
Program Number: 3864 Poster Board Number: C0269
Presentation Time: 3:45 PM–5:30 PM
Factors Predicting King-Devick Test Performance in Adults and
Adolescents
Yi Pang1, Robert J. Steinmetz2, Danielle F. Leong3, 2, Leonard V.
Messner1, Sherry Audycki4, James Fanelli5, Dan McGehee6, Wendy
Stone1, Katherine Lynch1, Heather Moss7. 1Illinois Coll of Optom,
Chicago, IL; 2SoLo Eye Care, Chicago, IL; 3King-Devick Test,
LLC, Oakbrook Terrace, IL; 4Advanced Eye Center, Bedford, MA;
5
Cape Fear Eye Institute, Wilmington, NC; 6Swagel Wootton Hiatt
Eye Center, Mesa, AZ; 7Department of Ophthalmology and Visual
Sciences and Department of Neurology & Rehabilitation, University
of Illinois at Chicago School of Medicine, Chicago, IL.
Purpose: The King-Devick (K-D) test is a rapid number naming test
that has been studied extensively as a marker of neurological disease
and concussion. Potentially confounding variables have not been
studied in a large sample. The purpose of this study was to determine
important confounding variables that are associated with K-D test
performance.
Methods: In this cross-sectional, multi-center study, subjects ≥15yrs
old with binocular near visual acuity < 20/30 completed two trials of
the K-D test protocol. Exclusion criteria included concussion within
3-months, post-concussion syndrome, dyslexia or neuro-degenerative
disorders. History of concussion, amblyopia, strabismus as well
as demographic variables of education, race/ethnicity, gender and
age were assessed by subject interview. Multiple linear regression
analysis was performed. Independent variables were modeled as
categorical (age (< or > 40 years), race/ethnicity, gender, education,
concussion, amblyopia, strabismus) and continuous (age in years
greater than 40 years) terms.
Results: Subjects (n=691, age 39.8±17.7 years) were enrolled across
5 sites. The average best K-D time was 41.2±8.2s. Table 1 shows the
results of multiple regression analysis. The final multiple regression
model included age beyond 40 years, education, black race and
Hispanic race. With other variables held constant, the K-D test time
worsened by 0.27s for each year in age above 40, improved by 1.94s
for each category of higher education level achieved, worsened by
3.67s for black race and improved by 2.38s for Hispanic ethnicity.
Gender, White race, Asian race, amblyopia, strabismus, or history of
concussion was not associated with K-D test performance.
Conclusions: Age greater than 40 years, education, black race
and Hispanic ethnicity were significantly associated with K-D test
performance. Knowledge of these confounding variables is important
for applications of K-D test in neurologically diseased populations
and its development as a clinical measurement tool.
Commercial Relationships: Yi Pang, None; Robert J. Steinmetz,
None; Danielle F. Leong, King-Devick Test, LLC (E); Leonard V.
Messner, None; Sherry Audycki, None; James Fanelli, None; Dan
McGehee, None; Wendy Stone, None; Katherine Lynch, None;
Heather Moss, None
Program Number: 3865 Poster Board Number: C0270
Presentation Time: 3:45 PM–5:30 PM
THE MULTIPLE RAREBIT TEST (DIGITSTEP):
FEASIBITILY STUDY IN A PEDIATRIC POPULATION
Danielle Coury1, Julie Racine2, David Rogers1, 2. 1Ophthalmology,
The Ohio State University, Columbus, OH; 2Ophthalmology,
Nationwide Childrens Hospital, Columbus, OH.
Purpose: PURPOSE:
In adult patients, assessment of vision is often measured by visual
acuity alone. Although suitable to detect optical defect, visual acuity
may fail to detect anomalies of the retina and/or the optic nerve.
Alternative tests such as the Humphrey visual field (HVF) and the
contrast sensitivity test (CST) have been used to address the above.
More recently, a new technique was developed, the multiple rarebit
test, to quickly address neuronal damage in patients with optic nerve
anomalies. The multiple rarebit test has been used in adults with
success, but has not been used in pediatric populations. Therefore,
the purpose of this study was to 1- assess the feasibility of this new
method in a pediatric population and 2- to compare the results with
other methods such as the VF and the CST.
Methods: METHODS:
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Ten subjects aged between 5 and 10 years of age with no known
ophthalmic pathology were recruited from the Nationwide Children’s
Hospital eye clinic to participate. Four tests were obtained for
all participants: Snellen visual acuity (VA), Humphrey visual
field (HVF), contrast sensitivity (CST) and multiple rarebit test
(Digitstep). All tests were performed monocularly and both eyes were
tested in the same session. Time to complete the test, ‘likeliness’ of
the test and the efforts needed to perform the test were compiled.
Results: RESULTS:
All subjects were able to perform all four tests. The VA, CST and the
Digitstep were well performed by subjects. Each test took less than 5
minutes to complete and subjects enjoyed the tests. On the other hand
HVF was very difficult to perform in younger patients (≤ 6y.o) and it
was time-consuming.
Conclusions: CONCLUSION:
The multiple rarebit test in a pediatric population is feasible. It is
easier for a child to perform the multiple rarebit test than to perform
the HVF. It is a quick test that children enjoyed. We noticed two
downsides of the test, first being the speed at which the numbers
are presented is fixed and can be sometimes too fast for the younger
subjects (≤6 years old) and second the digital numbers 2 and 5 are
similar in morphology and are often mistaken one another in children
younger than 6 years of age. In the future, the multiple rarebit test
could be use to asses the utility of the multiple rarebit test in children
affected with retinal or optic nerve damage.
Commercial Relationships: Danielle Coury, None; Julie Racine,
None; David Rogers, None
Support: The Ohio Lions Eye Research Foundation 319712
Program Number: 3866 Poster Board Number: C0271
Presentation Time: 3:45 PM–5:30 PM
Proper ordering and interpretation of studies to avoid diagnostic
delay in optic nerve sheath meningioma
Thomas Ableman, Steven A. Newman. Ophthalmology, University of
Virginia, Charlottesville, VA.
Purpose: Optic nerve sheath meningiomas are often discovered
after substantial delay. The fact that fractionated radiation therapy
may substantially improve the prognosis underlies the importance
of timely diagnosis and treatment. We performed a retrospective
analysis of 7 cases of optic nerve sheath meningiomas with
substantial diagnostic delay to identify the circumstances and pitfalls
which led to the delay.
Methods: Retrospective analysis of 7 cases of optic nerve sheath
meningiomas with substantial diagnostic delay including records,
imaging, and diagnostic studies
Results: In several cases significant progressive visual loss occurred
during the 1-10 year delay in diagnosis. Some of these reversed
with radiation therapy after definitive diagnosis and referral to the
interventional radiology service. : Four potentially preventable
problems resulting in diagnostic delay were identified:
1. Lack of ordering imaging studies often due to an alternative
diagnosis such as AION or papillitis.
2. Lack of appropriately directed imaging (head scans instead of
orbital scans, the lack of employment of fat sat and gadolinium).
3. Miss-reading requiring reinterpretation.
4. Misinterpretation of OCT data because blocked axonal transport
masks development of optic atrophy.
Conclusions: Advances in technology have improved our ability
to identify potentially treatable optic nerve sheath meningiomas.
However, it remains incumbent on the evaluating ophthalmologist
to be familiar with appropriate ordering and interpretation of such
studies to avoid diagnostic delay.
Commercial Relationships: Thomas Ableman, None; Steven A.
Newman, None
Program Number: 3867 Poster Board Number: C0272
Presentation Time: 3:45 PM–5:30 PM
Eye movement enhancement in Parkinson’s disease as a result of
CN-NINM intervention: a case study
Yakov Verbny, Kimberly Skinner, Mitchell Tyler, Kurt Kaczmarek, Yuri
Danilov. Biomedical Engineering, University of Wisconsin-Madison,
Madison, WI.
Purpose: The neurorehabilitation of sensory and motor functions
in Parkinson’s disease (PD) patients is undeveloped, and recovery
of eye-movement control is largely unexplored. There are very few
methods that show the possibility of rehabilitation of eye movements
affected by PD. The goal of this research was to investigate how well
cranial-nerve non-invasive neuromodulation (CN-NINM) can reduce
the effects of PD-induced impairments of oculomotor function and
help to recover eye movement control.
Methods: We completed a 4-month intervention with a 66-yearold male 6 years after he was diagnosed with PD symptoms. This
individual demonstrated abnormal gait, poor posture and balance,
occasional tremor and noticeable impairment of oculomotor function.
The CN-NINM intervention used a combination of both physical and
cognitive exercises with electrotactile stimulation to the tongue using
a Portable Neuromodulation Stimulator (PoNStm). Assessment of
oculomotor function was performed before and after the CN-NINM
intervention using special 4-channel binocular eye tracking goggles
(VisualEyes, Micromedical Inc). To evaluate the state of subject’s
eye movements we used three static nystagmus tests (vertical and
horizontal gaze, and spontaneous nystagmus) and three dynamic tests
(random saccade, smooth pursuit and optokinetic). All of the tests
were performed without tongue stimulation.
Results: The CN-NINM intervention resulted in the gradual
enhancement of patient eye movement control in all 6 tests. We
observed improvement of eye fixation, accuracy and stability in
nystagmus and gaze tests, increased eye movement accuracy and
precision, improved gain and velocity of target tracking, and changes
in both smoothness and synchronization of binocular movement
control in oculomotor tests. The most significant improvements in
eye movement control were found during performance of smooth
pursuit and random saccade testing. We also observed improvement
in his gait, posture and balance.
Conclusions: Our study establishes a proof of concept and
effectiveness of a new non-invasive neuromodulation therapy.
The improvements of eye movement control demonstrated by this
individual suggest that rehabilitation using a combination of exercise
and tongue-based neurostimulation may benefit people affected by
PD and would offer a novel treatment option for this disease.
Commercial Relationships: Yakov Verbny, None; Kimberly
Skinner, None; Mitchell Tyler, Advanced Neurorehabilitation
LLC,Madison,WI (I), Advanced Neurorehabilitation
LLC,Madison,WI (P), Advanced Neurorehabilitation
LLC,Madison,WI (S), Helius Medical Technologies, Newtown,
PA (I), Helius Medical Technologies, Newtown, PA (P), Helius
Medical Technologies, Newtown, PA (S), NeuroHabilitation Corp.,
Newtown, PA (P), NeuroHabilitation Corp., Newtown, PA (R); Kurt
Kaczmarek, Advanced Neurorehabilitation LLC,Madison,WI (I),
Advanced Neurorehabilitation LLC,Madison,WI (P), Advanced
Neurorehabilitation LLC,Madison,WI (S), Helius Medical
Technologies, Newtown, PA (I), Helius Medical Technologies,
Newtown, PA (P), NeuroHabilitation Corp., Newtown, PA (C),
NeuroHabilitation Corp., Newtown, PA (P), NeuroHabilitation Corp.,
Newtown, PA (R); Yuri Danilov, Advanced Neurorehabilitation
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
LLC,Madison,WI (I), Advanced Neurorehabilitation
LLC,Madison,WI (P), Advanced Neurorehabilitation
LLC,Madison,WI (S), Helius Medical Technologies, Newtown,
PA (I), Helius Medical Technologies, Newtown, PA (P), Helius
Medical Technologies, Newtown, PA (S), NeuroHabilitation Corp.,
Newtown, PA (C), NeuroHabilitation Corp., Newtown, PA (P),
NeuroHabilitation Corp., Newtown, PA (R)
Support: University of Wisconsin Foundation and the Jane Bradley
Pettit Foundation
Program Number: 3868 Poster Board Number: C0273
Presentation Time: 3:45 PM–5:30 PM
Higher prevalence of visual symptomatology in individuals with
Parkinson’s disease
Helene Kergoat1, 4, Estefania Chriqui1, 4, Caroline Law1, 4, Elizabeth
L. Irving3, Marie-Jeanne Kergoat4, 2, Bernard-Simon Leclerc5,
4
, Michel Panisset2, 6, Sylvain Chouinard2, 6, Ronald Postuma7,
8 1
. Optometrie, Universite de Montreal, Montreal, QC, Canada;
2
Medecine, Universite de Montreal, Montreal, QC, Canada; 3School
of Optometry and Vision Science, University of Waterloo, Waterloo,
ON, Canada; 4Institut universitaire de geriatrie de Montreal,
Montreal, QC, Canada; 5CSSS de Bordeaux-Cartierville–SaintLaurent-CAU, Montreal, QC, Canada; 6Centre hospitalier de
l’Universite de Montreal, Montreal, QC, Canada; 7Montreal General
Hospital, Montreal, QC, Canada; 8McGill University, Montreal, QC,
Canada.
Purpose: We have recently reported that the prevalence of visual
symptoms linked with convergence insufficiency (CI) was higher in a
group of individuals with Parkinson’s disease - PD (27%) compared
to those in an age-matched group without PD (9%). Here, we
investigated the prevalence of visual symptomatology in individuals
with vs without PD who, based on a co-existing oculovisual
condition, were excluded from participation in our original study. We
hypothesize that the prevalence would be higher in those with PD
than those without.
Methods: Two study groups (n= 82 each) were included: 1)
participants having PD (Avg. ± SD: 71.2 ± 10.4 yrs) recruited
from two specialized neurology departments, and 2) age-matched
participants not having PD (70.5 ± 9.2 yrs). These participants
had various oculovisual conditions (eg. strabismus, glaucoma)
excluding them from the CI study. The Convergence Insufficiency
Symptom Survey (CISS-15) was also used here to verify visual
symptomatology in the 2 study groups. A score of ≥ 21 is considered
positive for symptomatology. The CISS-15 and a detailed oculovisual
questionnaire were administered to each participant by a telephone
interview. Confidence intervals and t-tests were performed using
SPSS.
Results: The participants did not differ for age (p = 0.60). The results
indicated that 45.1% of participants with vs 17.1% of those without
PD presented a score of ≥21 on the CISS-15 questionnaire (p < 0.05).
Conclusions: We have previously shown that the prevalence of
visual symptoms is higher in individuals with vs without PD but
without a co-existing oculovisual condition. We demonstrate here that
this prevalence remains higher in individuals with vs without PD who
also have a co-existing oculovisual condition. These results indicate
that PD per se places individuals with the disease at greater risk of
visual symptomatology.
Commercial Relationships: Helene Kergoat, None; Estefania
Chriqui, None; Caroline Law, None; Elizabeth L. Irving, None;
Marie-Jeanne Kergoat, None; Bernard-Simon Leclerc, None;
Michel Panisset, None; Sylvain Chouinard, None; Ronald
Postuma, None
Support: Canadian Institutes of Health Research; Canadian
Optometric Education Trust Fund; Comité aviseur pour la recherche
clinique-Institut universitaire de gériatrie de Montréal
Program Number: 3869 Poster Board Number: C0274
Presentation Time: 3:45 PM–5:30 PM
Spectral-domain Optical Coherence Tomography in Huntington
Disease: Potential Biomarker?
Joao N. Beato1, Carlos Andrade2, Ana Monteiro2, Andreia Costa2,
Joana Guimarães2, Carolina Garrett2, Elisete Brandão1, Fernando
Falcão-Reis1, 3, Susana Penas1, 3. 1Ophthalmology, São João Hospital
Center, Porto, Portugal; 2Neurology, São João Hospital Center, Porto,
Portugal; 3Department of Sense Organs, Faculty of Medicine Of
University of Porto, Porto, Portugal.
Purpose: Clinical evaluation, neuroimaging, and biochemical
biomarkers have been extensively investigated in Huntington’s
disease, but none has been established. We performed a prospective
cross-sectional observational study to investigate retinal and
choroidal changes in HD and evaluate any potential correlation with
stage of the disease.
Methods: A thorough neurological evaluation was performed on
HD patients, including Motor Score of the Unified Huntington’s
disease rating scale (TMS-UHDRS), total functional capacity (TFC)
and independency status (IS). Age and sex matched healthy controls
enrolled were collected from the Ophthalmology Department
database. Both groups underwent examination through dilated pupil
using the Spectralis HRA+OCT®, Heidelberg® with the enhanced
depth imaging (EDI). Peripapillary RNFL and choroidal thickness
(PCT), macular and choroidal thickness (MT, CT) and respective
volumes (MV, CV) were evaluated.
Results: A total of 15 eyes of 8 HD patients were included. Sixteen
eyes of 8 healthy sex, age and mean refractive error-matched controls
were selected. Nasal RNFL, temporal PCT, superior peripheral
MT and MV and all macular choroidal thickness and volume
measurements were significantly (p<0.05) reduced in patients when
compared to controls. Several MT and MV measurements, were
positively correlated with TFC and IS and negatively correlated with
TMS-UHDRS, along with PCT measurements.
Conclusions: This findings suggest that both retina and choroid may
be affected in HD. Moreover, macular thickness and volume tend to
decrease with increasing severity of the disease. This could open a
way for the potential role of SD-OCT as a biomarker in HD.
Commercial Relationships: Joao N. Beato, None; Carlos Andrade,
None; Ana Monteiro, None; Andreia Costa, None; Joana
Guimarães, None; Carolina Garrett, None; Elisete Brandão,
None; Fernando Falcão-Reis, None; Susana Penas, None
Program Number: 3870 Poster Board Number: C0275
Presentation Time: 3:45 PM–5:30 PM
Alzheimer disease and Mild Cognitive Impairment assessment
using Optical Coherence Tomography
Miguel Castilla Marti1, Octavio Rodriguez Gomez1, Sergi Mojal
García2, Mercé Boada i Rovira1. 1fACE - Barcelona Alzheimer
treatment & research center, BArcelona, Spain; 2IMIM - Hospital del
Mar, BArcelona, Spain.
Purpose: Early markers are needed for experimental and clinical
diagnosis and follow-up of Alzheimer disease (AD) and earlier stages
as Mild Cognitive Impairment (MCI). Retinal Nerve Fiber Layer
(RNFL) thinning have been observed in AD and MCI patients. We
performed a prospective, observational clinical study to ascertain how
RNFL thickness, as measured by Optical Coherence Tomography
(OCT), can be correlated with different grades of cognitive
impairment.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Methods: All patients who came to our center during an open
door initiative carried out between September and October of
2014 were invited to participate in neurological and complete
neuropsychological examination, and then sorted between three
different diagnostic groups: Healthy controls (C), MCI and AD. All
patients who agreed undergone through a complete ophthalmological
examination, including measurements of RNFL and macular
thickness by OCT Model 3D OCT-1 Maestro (Topcon, Japan). All
statistical analyses were performed using the Statistical Package for
the Social Sciences (version 20.0; SPSS, Inc., Chicago, IL, USA)
Results: 200 eyes from 100 patients (38 Healthy controls, 41 MCI
and 21 AD) were included . Mean age for the whole sample was
67 years (SD=10.46) and 59.5 years for Control group, 67.71 for
MCI and 80.52 for AD. Those differences showed to be statistically
significant with a p value <0.001. No differences were observed on
Macular thickness between groups. RNFL measurements showed
to be different for overall thickness (p<0.001), superior (p<0.001),
temporal (p=0.002) and inferior (p=0.003) quadrants. Statistical
significance dissapeared when age adjustment was applied, resulting
the superior quadrant thickness values for each group (C=113.01mm,
MCI=111.67mm, AD=100.95mm) to be marginally significant
(p=0.070). When compared individually, AD group showed to be
statistically different from C (p=0.037) and MCI (p=0.024) on upper
quadrant, with no differences between MCI and Controls.
Conclusions: Data suggests a tendency to RNFL thinning on AD
patients. Nevertheless, age revealed to be the main factor related with
RNFL thinning in our series. If OCT is an appropriate method for
AD and MCI assessment, capable to discriminate between disease
and normal age related changes on retinal thickness layers, need to be
further evaluated.
Commercial Relationships: Miguel Castilla Marti, None; Octavio
Rodriguez Gomez, None; Sergi Mojal García, None; Mercé Boada
i Rovira, None
Program Number: 3871 Poster Board Number: C0276
Presentation Time: 3:45 PM–5:30 PM
Examination of retinal structure and visual function in civilian
patients with Traumatic Brain Injury
Jakaria Mostafa1, Divya Narayanan2, Suzanne Wickum1, Kassaundra
Johnston1, Nimesh B. Patel1, Laura J. Frishman1, Jason Porter1.
1
College of Optometry, University of Houston, Houston, TX;
2
Department of Ophthalmology, University of Texas Health Science
Center at San Antonio, San Antonio, TX.
Purpose: Recent reports suggest that veterans with traumatic brain
injury (TBI) may have optic nerve head (ONH) and inner retinal
damage in addition to reduced visual performance. We seek to (1)
quantify the extent to which abnormalities exist in retinal/ONH
structure and visual function in civilian TBI patients and (2) correlate
structural and functional measurements in the same eyes.
Methods: Spectral domain optical coherence tomography
volume scans of the ONH and macula were acquired in 14 eyes
of 7 TBI patients (36 ± 12 years). Peripapillary retinal nerve fiber
layer [RNFL] and macular retinal ganglion cell-inner plexiform
layer [GCIPL] thicknesses were quantified globally and in
sectors, and compared with instrument-based normative data.
Functional measurements were acquired with the full-field flash
electroretinogram (to quantify photopic negative response [PhNR]
amplitude) and 30-2 standard automated perimetry (to quantify mean
deviation [MD] and mean sensitivity). The percentage of agreement
between global structural and functional measures (i.e., whether
compared measures were both normal or abnormal) was calculated,
as was the probability of agreement when corrected for chance (AC1
statistics). Structural and functional measures were correlated on
global and local scales via regression analyses.
Results: GCIPL and RNFL thickness abnormalities were detected in
8/14 and 5/14 eyes, respectively. Abnormalities in PhNR amplitude
compared to normative values were found in 12/14 eyes and in MD
in 10/14 eyes. The strongest agreements occurred between PhNR
and MD (64% of eyes, AC1=0.42), GCIPL and RNFL thickness
(64%, AC1=0.31), and RNFL thickness and MD (64%, AC1=0.29).
Significant linear relationships (P<.05) were found across eyes
between GCIPL and RNFL thicknesses (R2 =0.62), MD and GCIPL
thickness (R2 =0.49), and MD and RNFL thickness (R2 =0.63). Only
9/56 comparisons were statistically significant when using published
structure-function correspondence maps to correlate sector measures
of GCIPL/RNFL thickness with corresponding local measures of
visual field sensitivity.
Conclusions: While structural abnormalities exist in some eyes, our
data indicate a high prevalence of functional abnormalities in TBI
patients. A better understanding of retinal/ONH structure, visual
function and their correlation in TBI patients may enable more
effective diagnosis, classification and treatment of injury.
Commercial Relationships: Jakaria Mostafa, None; Divya
Narayanan, None; Suzanne Wickum, None; Kassaundra
Johnston, None; Nimesh B. Patel, None; Laura J. Frishman,
None; Jason Porter, None
Support: NIH Grant P30 EY007551, Fight for Sight Summer
Student Fellowship, University of Houston College of Optometry
Program Number: 3872 Poster Board Number: C0277
Presentation Time: 3:45 PM–5:30 PM
Imaging of optic disc drusen: Swept-Source (SS)-OCT versus
B-scan ultrasound
Michelle Ahn1, Andrew W. Eller2, Bo Wang2, Ellen Mitchell2, Joel S.
Schuman2, Chen D. Lu3, Ireneusz Grulkowski3, James G. Fujimoto3,
Gadi Wollstein2, Gabrielle R. Bonhomme2. 1University of Pittsburgh
School of Medicine, Pittsburgh, PA; 2UPMC Eye Center, Eye and
Ear Institute, Ophthalmology and Visual Science Research Center,
Department of Ophthalmology, University of Pittsburgh School of
Medicine, Pittsburgh, PA; 3Department of Electrical Engineering
and Computer Science, and Research Laboratory for Electronics,
Massachusetts Institute of Technology, Cambridge, MA.
Purpose: Optic disc drusen are currently diagnosed by B-scan
ultrasonography, but this modality is difficult to maneuver,
uncomfortable to patients, and operator-dependent. The aim of this
prospective study was to determine whether an alternative imaging
technology, the Swept-Source (SS)-OCT, improves the ability to
identify optic disc drusen compared to the gold standard of B-scan
ultrasonography.
Methods: We recruited patients who were of 5 years of age or more
and diagnosed with anomalous optic nerve heads. Subjects received a
complete ophthalmologic exam of the anterior and posterior segments
as well as a B-scan ultrasound and SS-OCT. The prototype SS-OCT
system was operated at 1060nm wavelength with 100kHz axial
scan rate. Images from each of the two imaging technologies were
then independently and qualitatively assessed for the presence and
visibility of drusen.
Results: A total of 13 patients (4 males and 9 females) were
recruited. The average age was 47.6 years. Among these subjects,
there were 21 eyes with optic disc drusen. Drusen were confirmed
in B-scans by hyper-reflectance of the calcium deposits at low
gain. In the SS-OCT, they were hypo-reflective bodies that could
be visualized in a 3D cube, making it possible to also pinpoint their
locations. Optic disc drusen were identifiable through SS-OCT in
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
all 21 eyes (100%), had well-demarcated borders in 19 (90.5%), and
were seen along their entire depths in 16 (76.2%).
Conclusions: While the B-scan tests for the hyper-reflective
properties of the calcified bodies, the SS-OCT allows anatomic
visualization of the actual deposits. Here, we were able to identify
optic disc drusen in all of the eyes that were diagnosed with this
condition through B-scan. The SS-OCT therefore has equal ability to
detect drusen compared to B-scan ultrasonography, and the additional
benefits of ease of conducting the exam, patient comfort, data
standardization, and potential quantification of drusen size make it
more clinically useful.
Commercial Relationships: Michelle Ahn, None; Andrew W.
Eller, None; Bo Wang, None; Ellen Mitchell, None; Joel S.
Schuman, Zeiss (P); Chen D. Lu, None; Ireneusz Grulkowski,
None; James G. Fujimoto, Optovue (I), Zeiss (P); Gadi Wollstein,
None; Gabrielle R. Bonhomme, None
Support: NIH R01-EY013178, R01-EY011289, P30 EY008098; Eye
and Ear Foundation (Pittsburgh, PA); Research to Prevent Blindness
(New York, NY)
Program Number: 3873 Poster Board Number: C0278
Presentation Time: 3:45 PM–5:30 PM
Macular Edema Associated with Anterior Ischemic Optic
Neuropathy: An OCT Study
Christopher Weaver, Steven A. Newman. Ophthalmology, University
of Virginia, Charlottesville, VA.
Purpose: Thickening of nerve fiber layer is characteristic of anterior
ischemic optic neuropathy. Disc edema, if severe enough, can track
into the macula. This may be responsible for some of the decreased
vision seen in acute anterior ischemic optic neuropathy. To study the
incidence of effect of macular swelling, a retrospective study was
undertaken of patients with anterior ischemic optic neuropathy that
had OCT of both nerve fiber layer and macula.
Methods: A retrospective chart review was performed of longitudinal
data from the University of Virginia from December 2005- January
2014 with inclusion criteria consisting of the diagnosis of AION
and exclusion criteria of pre-existing macular edema from other
comorbidities (n=127).
Results: Of the 127 patients reviewed in this study, 14 had macular
edema as demonstrated on macular OCT (11%), which invariably
resolved over the course of approximately three months. These
patients had improved mean outcomes in visual acuity relative to
those without macular edema, in comparison to baseline visual acuity
in both groups (p<0.05).
Conclusions: Macular edema associated with AION was found in
11% of patients, with these patients demonstrating improvement
in visual acuity at three months compared to those patients who
presented without macular edema. Further studies investigating the
possible correlation between retinal nerve fiber layer thickness and
presence of macular edema are warranted given the uncertainty of the
inciting factors in the development of macular edema in AION.
Commercial Relationships: Christopher Weaver, None; Steven A.
Newman, None
Program Number: 3874 Poster Board Number: C0279
Presentation Time: 3:45 PM–5:30 PM
Multicolour Imaging in Acute Macular Neuro-retinopathy
Rashi Arora4, 2, Sara Vaz-Pereira1, 3, Gabriella De Salvo2. 1Hospital
de Santa Maria, Lisbon, Portugal, Lisbon, Portugal; 2University
Hospital of Southampton, Southampton, United Kingdom; 3Faculty
of Medicine, University of Lisbon, Portugal, Lisbon, Portugal;
4
Moorfields Eye Hospital, London, United Kingdom.
Purpose: To evaluate the role of multicolor imaging (MC) in the
diagnosis and follow up of acute macular neuroretinopathy (AMN)
and to compare its features to fundus color photograph, near-infrared
reflectance (NIR) and spectral domain optical coherence tomography
(SD-OCT).
Methods: Color fundus photographs, MC, NIR and SD-OCT were
performed in 5 patients who presented with central scotoma and
without any specific visible fundus features.
Results: AMN was identified as an area of hypo-reflectance in NIR
in 8 eyes of 5 patients. SD-OCT confirmed its location in the outer
retina below the outer plexiform layer in 7 eyes (type 2) and above
the outer plexiform layer in 1 eye (type 1). Additional MC was
performed at baseline in 5 eyes (3 patients) and at follow-up in all
eyes. Subsequent follow up demonstrated improvement of symptoms
and this was objectively confirmed on both NIR and MC by gradual
decrease of hypo-reflectance, with the latest showing higher contrast
between the affected and the physiologic areas. SD-OCT showed a
partial recovery of the ellipsoid zone in type 2 and inner nuclear layer
thinning in type 1.
Conclusions: MC is a new non invasive imaging modality which
allows the detection of fine anatomic retinal details. In our patients,
MC imaging emerged as a very useful tool in the detection and
follow-up of AMN. We believe that, when available, MC should be
routinely used to complement SD-OCT in the diagnosis and follow
up of this rare inflammatory condition.
Commercial Relationships: Rashi Arora, None; Sara Vaz-Pereira,
None; Gabriella De Salvo, None
Program Number: 3875 Poster Board Number: C0280
Presentation Time: 3:45 PM–5:30 PM
OPA1 sequencing analysis and detailed ophthalmic examinations
including the investigation of microcystic macular edema in 18
patients with bilateral optic atrophy
Shuhei Kameya1, Kiyoko Gocho1, Sachiko Kikuchi1, Kenichi Yoshino2,
Masahiro Miura3, Hiroko Yamazaki4, Kei shinoda5, Atsushi Mizota5,
Kunihiko Yamaki1, Hiroshi Takahashi6. 1Ophthalmology, Chiba
Hokusoh Hosp Nippon Med Sch, Inba, Japan; 2Yoshino Eye Clinic,
Taito-ku, Japan; 3Ophthalmology, Tokyo Medical University Ibaraki
Medical Center, Ami, Japan; 4Ophthalmology, Kohnodai Hospital,
National Center for Global Health and Medicine, Ichikawa, Japan;
5
Ophthalmology, Teikyo University School of Medicine, Itabashi-ku,
Japan; 6Ophthalmology, Nippon Medical School, Bunkyo-ku, Japan.
Purpose: Autosomal dominant optic atrophy (ADOA), also known
as Kjer’s disease, is the most common hereditary ocular neuropathy.
ADOA is characterized by a decrease in the visual acuity that
develops in childhood, temporal palor of the optic discs, centrocecal
scotoma, and color vision defects. The purpose of this study was to
distinguish patients with ADOA and optic atrophy with unknown
origin by comparing the results of OPA1 sequencing analysis and
clinical characteristics of the patients.
Methods: 18 patients with bilateral optic atrophy underwent detailed
ophthalmic examinations. The ophthalmological examinations
included measurements of the best-corrected visual acuity, fundus
photography, perimetry, SD-OCT analysis of nerve fiber layer
thickness, color vision test, differences of severity between right and
left eyes, and investigation of microcystic macular edema (MME)
in SD-OCT. 12 patients underwent an adaptive optics analysis for
detailed examination of MME. Mutational screening of all coding
and flanking intron sequences of the OPA1 gene in 18 patients was
performed by sanger DNA sequencing.
Results: We have identified pathological mutations of OPA1 gene in
7 patients from 5 families. All patients with OPA1 mutation revealed
temporal palor of optic discs, centrocecal scotoma or blind spot
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
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ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
enlargement binoculary. 6 patients with OPA1 mutation showed color
vision deficiency. All patients with OPA1 mutation revealed very thin
retinal nerve fiber layer between optic nerve and macular by a vertical
SD-OCT scan at about 1 mm from the edge of optic disc. Majority
of patients without OPA1 mutation lack some of these observations
commonly found in patients with OPA1 mutation. MME in SD-OCT
was found in 2 patients with OPA1 mutation and 2 patients without
OPA1 mutation. Adaptive optics analysis revealed MME in 2 patients
with OPA1 mutation and 2 patients without OPA1 mutation.
Conclusions: A vertical SD-OCT scan at about 1 mm from the edge
of optic disc is useful way to visualize and evaluate the temporal
palor of optic disc that is a remarkable feature of ADOA. MME
were identified in both groups with and without OPA1 mutation.
Since sanger sequencing could not detect a large deletion of the
gene, further studies such as multiplex ligation-dependent probe
amplification will be needed.
Commercial Relationships: Shuhei Kameya, None; Kiyoko
Gocho, None; Sachiko Kikuchi, None; Kenichi Yoshino, None;
Masahiro Miura, None; Hiroko Yamazaki, None; Kei shinoda,
None; Atsushi Mizota, None; Kunihiko Yamaki, None; Hiroshi
Takahashi, None
Program Number: 3876 Poster Board Number: C0281
Presentation Time: 3:45 PM–5:30 PM
Characteristics of microcystic macular edema determined by
adaptive optics scanning laser ophthalmoscopy (AO-SLO) in eyes
with optic neuropathy
Takao Endo1, Takashi Fujikado2, Masakazu Hirota2, Hiroyuki Kanda2,
Takeshi Morimoto2, Shinichi Usui1, Kohji Nishida1. 1Department
of Ophthalmology, Osaka Univ Grad School of Med, Suita, Japan;
2
Applied Visual Science, Osaka Univ Grad School of Med, Osaka,
Japan.
Purpose: Microcystic macular edema (MME) is detected as an
arcuate-shaped low reflectance area in the macula in the infrared
fundus photographs and in the adaptive optics scanning laser
ophthalmoscopic (AO-SLO) images. The low reflectance area
corresponds to the area of microcystic changes in the inner nuclear
layer (INL) detected by optical coherence tomography (OCT), and
they have been reported in a variety of optic nerve diseases. The
purpose of this study was to determine whether MME was present in
eyes with optic neuropathy and to determine their characteristics.
Methods: This was a retrospective study of 41 eyes of 25 patients
with optic neuropathy or glaucoma. There were 7 eyes with traumatic
optic neuropathy, 3 eyes with ischemic optic neuropathy, 4 eyes with
ethambutol optic neuropathy, 4 eyes with Leber’s optic neuropathy,
5 eyes with optic neuritis, 6 eyes with optic nerve atrophy and 12
eyes with glaucoma. All of the patients were examined by AO-SLO
and OCT at the Osaka University Hospital between August 2013
and October 2014. The visual acuity and incidence of MME were
determined in these patients.
Results: Low-reflectance areas in the AO-SLO image with
microcysts in the OCT images were observed in 11 eyes (26.8%). The
visual acuity was significantly poorer in eyes with MME (1.9±1.2
logMAR units) than in eyes without MME (0.42±0.73 log units;
P<0.0). Eight of the 11 eyes with MME had arcuate low reflectance
area but 3 eyes with glaucoma had a nerve fiber layer defect
(NFLD)-like low reflectance area by AO-SLO. This NFLD-like low
reflectance area did not correspond to the scotoma in the Humphery
visual fields, which were different from the ordinal NFLD.
Conclusions: The presence of MME may be related to an advanced
stage of optic neuropathy. The shape of the MME in the AO-SLO
images is not only arcuate but can also be NFLD-like.
Commercial Relationships: Takao Endo, None; Takashi Fujikado,
None; Masakazu Hirota, None; Hiroyuki Kanda, None; Takeshi
Morimoto, None; Shinichi Usui, None; Kohji Nishida, None
Program Number: 3877 Poster Board Number: C0282
Presentation Time: 3:45 PM–5:30 PM
A Decade Of Diagnosing Inherited Retinal Dystrophies and Optic
Atrophies: The Evolution Towards An Advanced Standardized
Retinal Imaging and Molecular Genetic Approach
Ulrich Kellner1, 2, Heidi Stöhr3, Susanne Kohl4, Bernhard H. Weber3,
Bernd Wissinger4, Teresa Neuhann5, Silke Weinitz1, 2, Ghazaleh
Farmand1, Simone Kellner1, 2. 1Rare Retinal Disease Center,
AugenZentrum Siegburg, MVZ ADTC Siegburg GmbH, Bonn,
Germany; 2RetinaScience, Bonn, Germany; 3Institute for Genetics,
Regensburg, Germany; 4Molecular Genetics, Institute for Ophthalmic
Research, Tübingen, Germany; 5Molekulargenetisches Zentrum
(MGZ), München, Germany.
Purpose: An early diagnosis of inherited retinal or optic nerve
disorders (IROD) is frequently delayed due to unspecific clinical
signs, variability of clinical manifestations and the underlying genetic
defects. The present study evaluates the impact of non-invasive
retinal imaging techniques (fundus autofluorescence (FAF), nearinfrared autofluorescence (NIA), spectral domain OCT (SD-OCT),
three wavelength MultiColor spectral reflectance imaging (MC)) and
molecular genetic analysis on the diagnostic process of IROD.
Methods: In a single specialized center 1045 patients with IROD
were examined and confirmed based on electrophysiological, retinal
imaging or molecular genetic data between 2004 and 2014. Followup was available in 378 patients (median 3.9 y.). In addition to the
basic ophthalmological examination electrophysiological testing
(ERG n=358; EOG n=53; VEP n=102; mfERG n=283) and noninvasive retinal imaging (FAF n=947; NIA n=698; SD-OCT n=621;
MC n=242) were performed at least once. Molecular genetic analysis
was performed in 545 patients.
Results: The combination of non-invasive retinal imaging
with molecular genetic analysis has continuously replaced
electrophysiological testing as a primary tool for the diagnosis of
IROD. Multiple novel imaging phenomena have been observed
specific for IROD, although frequently not specific for certain
associated genes. Early phenomena in retinal imaging modalities
frequently precede ophthalmoscopic visible alterations and therefore
facilitate early diagnosis. Mostly in cone dysfunction and congenital
stationary night blindness ERG is superior to retinal imaging.
Molecular genetic testing confirmed disease-causing mutations (1
in dominant or x-linked disorders, 2 in recessive disorders) in 229
patients (44.4%).
Conclusions: Non-invasive retinal imaging techniques advanced
towards the primary tool for the diagnostic approach in suspected
IROD and serve as the basis for planning of molecular genetic
analysis. Multiple novel characteristic retinal imaging phenomena
have been observed and increased our understanding of IROD.
Patients have the advantage that imaging techniques are more
widespread available than electrophysiological testing. A targeted
diagnostic strategy reduces the diagnostic delay, enables an earlier
counselling and therapy and avoids unnecessary diagnostic tests.
Commercial Relationships: Ulrich Kellner, None; Heidi Stöhr,
None; Susanne Kohl, None; Bernhard H. Weber, None; Bernd
Wissinger, None; Teresa Neuhann, None; Silke Weinitz, None;
Ghazaleh Farmand, None; Simone Kellner, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 3878 Poster Board Number: C0283
Presentation Time: 3:45 PM–5:30 PM
LSFG-measured reduction of temporal optic disc circulation in
ADOA patients
Maki Inoue, Noriko Himori, Takayuki Takeshita, Naoko Aizawa,
Kazuko Omodaka, Yukihiro Shiga, Kazuichi Maruyama, Koji
Nishiguchi, Toru Nakazawa. Tohoku university, Sendai, Japan.
Purpose: To evaluate optic nerve head microcirculation in autosomal
dominant optic atrophy (ADOA) patients with laser speckle
flowgraphy (LSFG), a recently introduced method to assess blood
flow.
Methods: This study comprised 14 eyes of 8 ADOA patients
(mean age: 37.7 ± 14.0 years; spherical equivalent: -3.66 ± 2.15 D;
LogMAR visual acuity: 0.51 ± 0.39). Clinically, the ADOA patients
were diagnosed by low visual acuity, pallid temporal optic nerve
discs, visual field defects, a family history consistent with autosomal
dominant inheritance and the presence of mutations in the OPA1
gene. Eighteen normal eyes of 9 age-matched subjects served as
controls (mean age: 41.6 ± 12.7 years; spherical equivalent: -3.11 ±
1.75 D; LogMAR visual acuity: -0.14 ± 0.05). Blood flow in the optic
nerve head was assessed with LSFG, and the mean blur rate (MBR)
ratio was calculated for each optic nerve head quadrant (superior,
temporal, inferior and nasal) by dividing tissue MBR in that quadrant
by the entire tissue MBR in the optic nerve head. We then compared
the MBR ratio in each quadrant in the two groups.
Results: In all quadrants, MBR was significantly lower in the ADOA
patients than in the controls (superior: 8.23 ± 1.50 vs. 13.84 ± 3.28;
temporal: 5.12 ± 1.02 vs. 10.33 ± 2.48, inferior: 7.04 ± 1.31 vs. 13.65
± 2.46, nasal: 8.70 ± 1.13 vs. 13.94 ± 2.32, respectively, p < 0.01).
Only in the temporal quadrant, the MBR ratio was significantly lower
in the ADOA patients (0.74 ± 0.09 vs. 0.82 ± 0.07, respectively, p <
0.05).
Conclusions: In ADOA, the temporal optic disc generally appears
pale in fundus imaging. This suggests that blood flow on the temporal
side of the optic disc should be reduced compared to other disc areas,
but precise measurements of blood flow in the optic nerve head of
ADOA patients have not yet been reported. Here, we found that blood
flow in the optic disc, particularly on the temporal side, was indeed
significantly lower in ADOA patients than in normal controls. Due to
the anatomical characteristics of the optic nerve, the papillomacular
bundle is susceptible to damage caused by mitochondrial dysfunction,
which occurs in ADOA. Thus, our results suggest that reduced
blood flow in the temporal optic disc in ADOA patients is caused by
damage to the papillomacular bundle.
Commercial Relationships: Maki Inoue, None; Noriko Himori,
None; Takayuki Takeshita, None; Naoko Aizawa, None; Kazuko
Omodaka, None; Yukihiro Shiga, None; Kazuichi Maruyama,
None; Koji Nishiguchi, None; Toru Nakazawa, None
Program Number: 3879 Poster Board Number: C0284
Presentation Time: 3:45 PM–5:30 PM
Peripapillary and subfoveal choroidal thickness in non-arteritic
anterior ischemic optic neuropathy (NA-AION)
Libin Jiang. Eye Center, Beijing Tongren Hospital, Beijing, China.
Purpose: To study whether peripapillary and subfoveal choroidal
thicknesses of NA-AION patients is normal or not.
Methods: The study involved 44 unilateral NA-AION patients
(23 men and 21 women), whose mean age was 50.84±9.95 years
(mean±SD), and 60 normal subjects (60 eyes) with similar age
(50.30±1.18 years) and diopter. The patients were divided into
two groups: 19 patients with optic disc edema in group 1 and 25
patients with optic disc edema resolution in group 2. Peripapillary
and subfoveal choroidal thicknesses in all the eyes studied were
measured by enhanced depth imaging Heiderberg Spectralis optic
coherence tomography (EDI-OCT, Heidelberg engineering, Software
Version:5.3.2). Peripapillary choroidal thickness was measured at the
nasal superior (NS), nasal (N), nasal inferior (NI), temporal inferior
(TI), temporal (T) and temporal superior (TS) segments. Choroidal
thicknesses in the suffering eyes and the unaffected fellow eyes of
the patients were compared with that of normal subjects. Choroidal
thicknesses of the patients in Group 1 and Group 2 were also
compared. The correlation between choroidal thickness and retinal
nerve fiber layer (RNFL) thickness, logMAR visual acuity (logMAR
VA), and the mean defection (MD) of Humphrey static perimetry (242) in the NA-AION suffering eyes were analyzed.
Results: It was only found that peripapillary choroidal thickness
at the nasal, nasal inferior and temporal inferior segments in the
suffering eyes in group 1 were significantly thicker than that of
normal subjects (P<0.05). We found no difference in choroidal
thickness (1) between the suffering eyes and the unaffected fellow
eyes of the NA-AION patients, (2) between the unaffected fellow eye
of the NA-AION patients and normal eyes of healthy subjects, (3)
between group 1 and group 2 (all P>0.05). There were no correlations
between choroidal thickness and RNFL thickness in both two groups
(all P>0.05). Neither logMAR VA nor MD correlated with choroidal
thickness in the eyes affected by NA-AION (all P>0.05).
Conclusions: Although peripapillary choroidal thickness in some
segments become thicker in the eyes with optic disc edema caused by
NA-AION, there are no evidences to prove that choroidal thickness is
abnormal in NA-AION compared with normal subjects with similar
age and diopter.
Commercial Relationships: Libin Jiang, None
Program Number: 3880 Poster Board Number: C0285
Presentation Time: 3:45 PM–5:30 PM
Serum Level of Vascular Endothelial Growth Factor and
Opening Lumbar Pressure Significantly Correlated with Optic
Disc Edema in Patients with POEMS Syndrome
Takehito Iwase, Hirotaka Yokouchi, Takayuki Baba, Toshiyuki
Oshitari, Shuichi Yamamoto. Japanese Ophthalmological Society,
Chiba, Japan.
Purpose: It has been shown that the intracranial pressure (ICP) can
induce optic disc edema (ODE), and high serum levels of vascular
endothelial growth factor (VEGF) can also induce ODE in patients
with polyneuropathy, organomegaly, endocrinopathy, monoclonal
gammopathy, and skin changes (POEMS) syndrome. We performed
a cross sectional observational study to determine whether there is
a significant correlation between the peripapillary retinal nerve fiber
layer (RNFL) thickness and the serum level of VEGF and the spinal
lumbar pressure (LP).
Methods: We studied 32 eyes of 16 treatment-naïve patients (11
men, 5 women) with the POEMS syndrome at the Chiba University
Hospital from September 2012 through October 2014. The diagnosis
of POEMS was made by the criteria established by Dispenzieri in
2007. The peripapillary RNFL (pRNFL) thickness was determined
by optical coherence tomography (OCT: RTVue-100 Optovue, Inc.).
The serum level of VEGF was measured by enzyme-linked immune
sorbent assay (ELISA). The opening (LP) pressure was measured
instead of the ICP. The correlation between the pRNFL thickness and
the serum level of VEGF and opening LP pressure was determined by
the Spearman’s rank-correlation coefficient.
Results: The mean serum level of VEGF was 5130 ± 3590 pg/
ml with a range of 1330 to 11900 pg/ml. The mean opening LP
pressure was 179.1 ± 56.4 mmH2O. There was a significant positive
correlation between the pRNFL thickness and the opening LP
pressure (r=0.67, P=0.0002), and also between the pRNFL thickness
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
and the serum level of VEGF (r=0.37, P=0.03). In addition, there
was a strong positive correlation between the pRNFL thickness
of the right and left eyes (r = 0.81, P=0.0001). On the other hand,
the correlation between the serum level of VEGF and opening LP
pressure was not significant (r=0.32,P=0.32).
Conclusions: The significant positive correlation between the pRNFL
thickness and the opening LP and also with the serum levels of VEGF
are in accord with previous studies reporting that the ICP and the
serum levels of VEGF can affect the ODE in POEMS patients. These
results suggest that both the higher LP and the serum levels of VEGF
can account for the development of ODE in patients with POEMS
syndrome.
Commercial Relationships: Takehito Iwase, None; Hirotaka
Yokouchi, None; Takayuki Baba, None; Toshiyuki Oshitari, None;
Shuichi Yamamoto, None
Program Number: 3881 Poster Board Number: C0286
Presentation Time: 3:45 PM–5:30 PM
Characterizing optic disc edema in the setting of neurosyphilis
John J. Chen1, Matthew Thurtell2. 1Ophthalmology, Mayo Clinic,
Rochester, MN; 2Ophthalmology, University of Iowa, Iowa City, IA.
Purpose: Syphilis can affect any part of the eye, including the optic
nerve. Patients can have disc edema without visual compromise,
which has been attributed to papilledema from raised intracranial
pressure or optic perineuritis from optic nerve sheath inflammation.
However, these attributions were proposed before MRI was largely
available. We performed a retrospective, clinical observational
study to better understand the mechanism of optic disc edema in
neurosyphilis.
Methods: We reviewed all patients seen at the University of Iowa
from 2010 to 2014 with a diagnosis of neurosyphilis affecting the
optic nerve, which revealed three patients with optic disc edema. The
visual acuity, fields, OCT, fundus photos, lumbar puncture, and MRI
results were examined to determine the mechanism of the optic disc
edema. Neurosyphilis was confirmed with reactive VDRL in the CSF.
Results: One patient had unilateral optic disc edema and two patients
had bilateral optic disc edema. The visual fields showed enlargement
of the blind spots only, except for one eye of a patient who had
concomitant chorioretinitis and trace optic disc edema resulting
in a cecocentral scotoma. All three patients denied symptoms of
raised intracranial pressure. The opening pressure was normal in
the two patients who had it measured; the opening pressure in the
patient with unilateral disc edema was not measured. MRI of the
orbits demonstrated no optic nerve sheath enhancement in any of the
patients.
Conclusions: With modern diagnostic imaging, we were able to
demonstrate a lack of optic nerve sheath enhancement in three
patients with optic disc edema and preserved visual function,
suggesting papillitis may be a better term than optic perineuritis in
many cases of isolated disc edema from neurosyphilis.
62 year-old male with bilateral optic disc edema in the setting of
neurosyphilis. The right eye has severe optic disc edema with normal
visual fields other than enlargement of the blind spot. The left eye
has a cecocentral scotoma due to chorioretinitis in conjunction with
trace optic disc edema. OCT shows an elevated retinal nerve fiber
layer thickness in both eyes, right greater than left, and photoreceptor
disruption in the macula of the left eye confirming chorioretinitis.
Magnetic resonance imaging of the orbit demonstrates no optic nerve
or sheath enhancement.
Commercial Relationships: John J. Chen, None; Matthew
Thurtell, None
Program Number: 3882 Poster Board Number: C0287
Presentation Time: 3:45 PM–5:30 PM
Current intensity-dependent neuroprotection in eyes with
traumatic optic neuropathy by transcorneal electrical stimulation
Takeshi Morimoto1, Takao Endo2, Kohji Nishida2, Takashi Fujikado1.
1
Applied Visual Science, Osaka Univ Graduate Sch of Med, Suita,
Japan; 2Ophthatmology, Osaka University Graduate School of
Medicine, Suita, Japan.
Purpose: To determine whether the improvement of the visual acuity
in eyes with traumatic optic neuropathy (TON) is associated with the
current intensity of transcorneal electrical stimulation (TES).
Methods: This was a prospective, randomized, partially blinded,
clinical trial of 27 patients at the Osaka University Hospital. All
patients had TES (10 ms, biphasic pulses, 20 Hz) for 30 min once a
month in their TON eyes for 6 months. The patients were randomly
divided into two groups; 1.0 mA (n = 17) or 0.3 mA (n = 9). The
primary outcome measurement was the change in the best-corrected
visual acuity (BCVA) at 3 and 6 months after the start of the TES
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
treatment. An improvement in visual acuity was defined as a change
of ≥0.2 logarithm of the minimum angle of resolution (logMAR)
units. The changes in the BCVA in the two groups were compared.
Results: The improvement in the BCVA in the 0.3 mA group was
0.10 ± 0.085 logMAR units and that in the 1.0 mA group was 0.11 ±
0.049 logMAR units at 3 month (P=0.73). The improvement in the
BCVA at 6 month in the 0.3 mA treatment group was 0.04 ± 0.085
logMAR units which was significantly less than that in the 1.0 mA
group of 0.26 ± 0.049 (P=0.039) logMAR units. The improvement
of the BCVA was found in 22.2% of the patients in the 0.3 mA
group and 23.5% of the patients in the 1.0 mA group at 3 months,
and 22.2% in the 0.3 MA group and 47.1% in the 1.0 mA group at 6
months. The differences were not statistically significant (P=0.94 and
P=0.21, respectively).
Conclusions: TES at 1.0 mA can improve the VA in patients with
TON more effectively than at 0.3 mA. These results indicate that
there is probably an optimal neuroprotective current intensity of TES
for eyes with TON. These value will provide a guideline for the use
of TES in patients with TON. Further studies with larger sample sizes
and longer duration are needed to confirm the findings and to define
the optimal stimulation parameters.
Commercial Relationships: Takeshi Morimoto, None; Takao
Endo, None; Kohji Nishida, None; Takashi Fujikado, None
Support: Japanese government grant 22791658
Clinical Trial: UMIN000005049
Program Number: 3883 Poster Board Number: C0288
Presentation Time: 3:45 PM–5:30 PM
Diagnostic performance of ganglion cell and retinal nerve fiber
layer thickness in alcoholic optic neuropathy
Stéphanie Michau1, Pascal Perney2, Hélène Donnadieu-Rigolle2,
Max Villain1, Vincent Daien1. 1Ophtalmology, University Hospital of
Montpellier, Montpellier, France; 2Addictology, University Hospital
of Montpellier, Montpellier, France.
Purpose: To explore the diagnostic performance of optic nerve
parameters in early alcoholic optic neuropathy.
Methods: 395 eyes of 200 patients were included prospectively
during hospitalisation for alcohol withdrawal from January 2010
to October 2013 in the University Hospital of Montpellier. The
definition of alcoholic optic neuropathy was the assocation of
alterated visual field with impaired color vision. Optic nerve
variables were assessed by visual-evoked potential, Heidelberg
Retina Tomograph III (HRT-III), spectral-domain optic coherence
tomography (SD-OCT) (ganglion cell layer [GCL] and retinal nerve
fiber layer [RNFL]) and scanning laser polarimetry (GDx). Optic
nerve variables were compared between patients with and without
optic neuropathy by age- and sex-adjusted analysis of covariance.
Diagnostic performance was determined by area under the receiver
operating characteristic curve (AUC), sensitivity and specificity.
Results: In total, 47 (24%) patients presented alcoholic ON (mean
(SD) age of 47 (11) years; 33 men). Peripheral neuropathy was more
frequent in patients with than without alcoholic ON (p<.001) and
GCL and RNFL were thinner (mean (SD) of 12.91 (0.7) vs 14.78
(0.3) mm, p=0.015; and 90.27 (2.1) vs 99.57 (1.08) mm, p<.001,
respectively). The AUC was highest for superior GCL (AUC=0.78;
(95% CI, 0.67-0.89)) and global RNFL thickness from SD-OCT
(AUC=0.72; (95% CI 0.62-0.82)) and had the best sensitivityspecificity pair 82.1–62.0% and 79.4–63.4%, respectively. The AUC
for GDx and HRTIII ranged from 0.52 to 0.68.
Conclusions: Objective examination including GCL and RNFL
thickness on SD-OCT could be useful to improve the diagnostic of
alcoholic ON.
Commercial Relationships: Stéphanie Michau, None; Pascal
Perney, None; Hélène Donnadieu-Rigolle, None; Max Villain,
None; Vincent Daien, None
Program Number: 3884 Poster Board Number: C0289
Presentation Time: 3:45 PM–5:30 PM
Comparison of retinal nerve fiber layer thickness measurement
by Stratus and Cirrus OCTs in retrobulbar optic neuritis and
non arteritic anterior ischemic optic neuropathy
Barbara Giambene, Gianni Virgili, Ugo Menchini, Stanislao Rizzo.
University of Firenze, Eye Clinic, Firenze, Italy.
Purpose: To compare retinal nerve fiber layer thickness (RNFLT)
measurement by Stratus and Cirrus OCTs and to evaluate the
agreement between the two instruments in retrobulbar optic neuritis
(RON), non arteritic anterior ischemic optic neuropathy (NAION)
and normals.
Methods: Eighty-nine eyes with RON, ninety-two with NAION
(both in the chronic phase, six to twelve months after diagnosis
of acute disease), and one hundred fifty-five normal eyes were
studied. Average RNFLT was measured by Stratus and Cirrus OCTs.
Comparisons among groups were performed by ANOVA test. The
agreement between the two instruments was assessed using intraclass
correlation coefficient (ICC) with 95% confidence interval (CI), and
Bland-Altman analysis. Statistical significance was set at p ≤0.5.
Results: Average RNFLT was lower in NAION eyes than in RON
and normal ones using both OCTs (60.0 ±1.2, 69.9 ±1.2 and 97.4
±0.9 m, p<0.001 by Cirrus; 49.7 ±1.5, 65.9 ±1.9 and 99.2 ±1.3 m,
p<0.001 by Stratus). RNFLT values were higher with Cirrus than
with Stratus in NAION (+10.30 μ, CI 7.82 – 12.79 μ) and RON
(+4.01 μ, CI 1.32 – 6.70 μ) eyes, and slightly lower in normal ones
(-1.75 μ, CI -3.51 – 0.01 μ). A stronger agreement between the two
instruments was found in normal and RON eyes than in NAION ones
(ICC 0.682, CI 0.566-0.771; 0.635, CI 0.467-0.758; 0.321, CI 0.1320.472, respectively).
Conclusions: Both Stratus and Cirrus OCTs can identify RNFLT
reduction in eyes with RON and NAION in the chronic phase.
Absolute RFNLT values differ between the two instruments, hence
they have not to be considered interchangeable.
Commercial Relationships: Barbara Giambene, None; Gianni
Virgili, None; Ugo Menchini, None; Stanislao Rizzo, None
Program Number: 3885 Poster Board Number: C0290
Presentation Time: 3:45 PM–5:30 PM
Predictive Value of Perioperative Circumpapillary Retinal Nerve
Fiber Layer Thickness in Primary Rhegmatogenous Retinal
Detachment Macular Anatomic Outcomes
Julia Kuhn1, Joseph Martel2. 1School of Medicine, University
of Pittsburgh, Pittsburgh, PA; 2Department of Ophthalmology,
University of Pittsburgh, Pittsburgh, PA.
Purpose: Despite successful rhegmatogenous retinal detachment
(RRD) surgery, postoperative macular edema, epiretinal membrane
(ERM) formation, and macular atrophy are difficult to predict, yet
important factors influencing final visual outcome. We performed
a retrospective observational clinical study to examine the
perioperative spectral domain optical coherence tomography (sdOCT)
circumpapillary retinal nerve fiber layer (cpRNFL) thickness as a
predictor for the development of postoperative macular disease in
patients undergoing successful RRD repair surgery.
Methods: A review of longitudinal data from 2009 – 2014 at the
University of Pittsburgh Medical Center identified 36 patients
having undergone successful primary RRD surgery without previous
posterior segment surgery, optic nerve disease, or macular disease,
and availability of preoperative and postoperative cpRNFL and
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
macular sdOCT imaging data. The nonoperative contralateral eye was
used for all group comparisons as a control. Statistical analyses were
performed using a two-tailed Student’s t test and Wilcoxon rank-sum
test.
Results: Of 36 patients who met inclusion criteria, 28 underwent
RRD repair with vitrectomy and 8 with scleral buckling. Median
follow-up time was 12 months (range 0.5-55 months), and mean
follow-up visits was 2.0 (range 1-10). Mean cpRNFL was 91.97mm
±14.73 in RRD eyes and 85.48mm ±12.09 in control eyes (p<0.0001).
Mean macular central subfield thickness (CST) was 325.51mm
±76.19 and 293.30mm ±59.21 in RRD and control eyes, respectively
(p=0.0076). For RRD patients who developed late postoperative
central macular edema (CST >300mm), median cpRNFL thickness
in the early postoperative period was significantly greater than for
RRD patients who did not develop late postoperative central macular
edema (p=0.0027). In RRD patients who developed late central
subfield macular thinning (CST<250mm), median cpRNFL thickness
was not found to be significantly less than in those patients who did
not develop macular thinning (p=0.9552).
Conclusions: Early perioperative cpRNFL thickening may be a
predictor for late postoperative macular edema in patients undergoing
successful RRD repair surgery. Relative cpRNFL thinning or
thickening was not predictive of central macular thinning.
Commercial Relationships: Julia Kuhn, None; Joseph Martel,
None
Program Number: 3886 Poster Board Number: C0291
Presentation Time: 3:45 PM–5:30 PM
Assessment of retinal nerve fiber layer thickness in healthy, full
term neonates
Mays El-Dairi1, Monica B. Sevilla1, Adam Rothman1, Sharon
Freedman1, 2, Amy Tong1, Vincent Tai1, Du Tran-Viet1.
1
Ophthalmology, Duke University Medical Center, Durham, NC;
2
Pediatrics, Duke University School of Medicine, Durham, NC.
Purpose: To measure average retinal nerve fiber layer (RNFL)
thicknesses in healthy, full term neonates.
Methods: Healthy infants born between 37-42 weeks post-menstrual
age were imaged with handheld spectral domain optical coherence
tomography (Bioptigen, Inc., Research Triangle Park, NC). A custom
MATLAB script (Mathworks, Inc., Natick, MA) segmented the
RNFL; the fovea and optic nerve center were manually selected.
A second script measured the average RNFL thickness along the
papillomacular bundle, defined as the arc from -15° to +15° on the
axis from the optic nerve to fovea, with radii of 1.1, 1.3, 1.5, and 1.7
mm from the center of the optic disc. Shapiro-Wilk W tests assessed
these measurements for normality to determine the age-appropriate
radial distance for subsequent analyses. Average RNFL thicknesses
for four temporal 45° sectors (superior temporal, temporal superior,
temporal inferior, and inferior temporal) as well as the temporal
quadrant were calculated and compared to demographic parameters
for all infants.
Results: Fifty full-term infants were adequately imaged for RNFL
analysis. RNFL thicknesses at 1.5 mm radial distance from the optic
nerve were the most normally distributed. While there was a trend
towards greater mean superior temporal RNFL thickness for both
Black and Hispanic versus White infants (128 ±27, 124 ±30, and 100
±19 μm, respectively, P=0.04 for both comparisons), there were no
other significant differences noted in RNFL thicknesses by race, sex,
gestational age, or birth weight.
Conclusions: We present RNFL thickness measurements for healthy,
full term infants that may serve as normative data for future analyses.
Commercial Relationships: Mays El-Dairi, None; Monica B.
Sevilla, None; Adam Rothman, None; Sharon Freedman, None;
Amy Tong, None; Vincent Tai, None; Du Tran-Viet, None
408 Eye movements
Wednesday, May 06, 2015 8:30 AM–10:15 AM
4CD Mile High Blrm Paper Session
Program #/Board # Range: 3993–3999
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Program Number: 3993
Presentation Time: 8:30 AM–8:45 AM
Absence of Intramuscular Elastin Correlates with Independent
Mechanical Behavior of Extraocular Muscle (EOM)
Compartments During Active and Passive Mechanical Loading
Andrew Shin, Lawrence H. Yoo, Joseph L. Demer. Ophthalmology,
Jules Stein Eye Institute, UCLA, Los Angeles, CA.
Purpose: Intramuscular innervation of horizontal rectus EOMs is
segregated into superior & inferior (transverse), compartments while
all EOMs are also divided into global (GL) & orbital (OL) layers
with scleral & pulley insertions. Mechanical coupling among EOM
compartments was investigated during passive tensile and active
loadings, and correlated with histological distribution of elastin, a
connective tissue constituent localized to high mechanical stress.
Methods: Bovine rectus EOMs were rapidly removed after slaughter.
For passive loading, one compartment was extended, while the other
was stationary, as forces in both channels were monitored. For active
contraction, the EOM was immersed in 50 mM CaCl2 labeled with
fluorescein while one compartment was coated with petrolatum to
prevent permeation; contraction was in the other compartment while
tensions in both channels were monitored. Fresh EOMs were then
sectioned transversely for yellow-green fluorescence photography
under blue light, and a formalin-fixed whole orbit was transversely
sectioned and stained with elastin van Geison stain for histology.
Results: There was abundant elastin in pulley tissues, but
intramuscular elastin only in blood vessels, not in intercompartmental
boundaries. (Fig. A). Fluorescein penetration confirmed selective
CaCl2 permeation inducing selective active contraction (Fig. B). For
both passive elongation and active contraction, intercompartmental
force coupling was always ≤10%. Active tensions in GL and OL
could change in opposite directions (Fig. C).
Conclusions: Absence of elastin in intercompartmental regions of
EOMs correlates with minimal active and passive force coupling.
Marked mechanical independence of EOM compartments under
both passive and active loading endows each EOM with potential
for separately controllable actions required by the active pulley &
transverse compartmental hypotheses.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
A. Low magnification cross section of lateral rectus muscle. A.(a)
Boundary between OL and GL. A(b) Pulley contains abundant elastin
(black). A(c) Elastin present only in blood vessel walls, not among
muscle fiber bundles.
B. Cross section showing fluorescein permeated only GL of lateral
rectus muscle. OL was coated by petrolatum.
C. in B. After initial buoyancy effect, force increased only in GL,
while decreasing in OL.
Commercial Relationships: Andrew Shin, None; Lawrence H.
Yoo, None; Joseph L. Demer, None
Support: NIH EY08313
Program Number: 3994
Presentation Time: 8:45 AM–9:00 AM
Whole Exome Sequencing Identifies a New Splicing Factor Gene
Causative of X-linked Spinocerebellar Ataxia
Mervyn G. Thomas1, Cris S. Constantinescu2, Viral Sheth1, Moira
Crosier3, Jayesh Patel4, Rob A. Dineen2, Paul Maddison2, Thabit
Sabbubeh2, Irene Gottlob1. 1The University of Leicester Ulverscroft
Eye Unit, University of Leicester, Leicester, United Kingdom;
2
Division of Clinical Neuroscience, University of Nottingham,
Nottingham, United Kingdom; 3MRC-Wellcome Trust Human
Developmental Biology Resource, Institute of Genetic Medicine,
Newcastle University, Newcastle, United Kingdom; 4Department of
Paediatric Neurology, Bristol Royal Hospital for Children, Bristol,
United Kingdom.
Purpose: The genetic basis of X-linked Spinocerebellar Ataxia
(SCA-X5: OMIM 300703) remains unclear, although previous
linkage analysis identified a candidate locus on Xq25-q27.1. We
identified a large family with a phenotype consistent with SCA-X5.
We aimed to use whole exome sequencing (WES) to identify the
causative gene, characterize the phenotype and the spatiotemporal
expression of the protein.
Methods: Detailed ophthalmic and neurological examinations
were performed. Eye movement recordings were used to assess eye
movement abnormalities using a series of fixation and smooth pursuit
tasks. MRI, nerve conduction studies, electromyography and muscle
biopsies were obtained from affected subjects. WES was performed
on a large three-generation family (6 affected). We identified rare
variants by focusing on protein-altering and splice-site changes with
an allele frequency <1% in SNP databases and absent from 56 local
exomes of unaffected subjects. Mutation was verified using sanger
sequencing. Spatiotemporal expression was characterized using
immunohistochemistry in human embryonic brain.
Results: Five subjects had variable vertical and horizontal conjugate
nystagmus with an increasing slow phase velocity. All affected
subjects had saccadic smooth pursuit, ataxia and mild learning
difficulties. Four subjects had abnormal head posture and strabismus.
Affected females had macro-square wave jerks. Visual acuity
ranged from 0.1-0.4 logMAR and stereopsis ranged between 110”
of arc to no detectable stereopsis. MRI studies revealed a variable
degree of cerebellar vermian atrophy, which was more severe in
the male subject (hemizygous mutation) compared to the females
(heterozygous mutation). Neuromuscular tests and investigations
were normal.
Variant filtering from WES dataset identified a splicing factor gene,
SRPK3 at Xq28, mutation of which was causative of SCA-X5. The
mutation co-segregated with the phenotype and was absent in the
control exomes and SNP databases. Expression was noted in the
developing cerebellum, with intense staining in the adjacent choroid
plexus epithelium.
Conclusions: For the first time we have identified the gene, SRPK3,
mutation of which is causative of SCA-X5. We have shown the
detailed phenotypical characteristics associated with SCA-X5,
with females less severely affected. We have also characterized the
spatiotemporal expression of this protein in the developing brain.
Commercial Relationships: Mervyn G. Thomas, None; Cris S.
Constantinescu, None; Viral Sheth, None; Moira Crosier, None;
Jayesh Patel, None; Rob A. Dineen, None; Paul Maddison, None;
Thabit Sabbubeh, None; Irene Gottlob, None
Support: Ulverscroft Foundation and Medical Research Council
Program Number: 3995
Presentation Time: 9:00 AM–9:15 AM
Accommodation and vergence during measurement of fusional
ranges in infants and pre-school children
Vidhyapriya Sreenivasan1, Erin Babinsky2, Yifei Wu1, T R. Candy1.
1
Optometry, Indiana University, Bloomington, IN; 2Universitat
Pompeu Fabra, Barcelona, Spain.
Purpose: Accurate binocular alignment requires motor fusion,
which must compensate for heterophoria. Infants and young children
experience uncorrected hyperopia and narrow IPDs that could lead
to excessive convergence (and esophoria) resulting from neural
coupling. How well are fusional reserves coping with this challenge?
This study evaluated accommodation and vergence behaviour of
infants and young children during measurement of vergence ranges to
determine fusional reserves around their phoria.
Methods: Purkinje image tracking and eccentric photorefraction
(MCS PowerRefractor) were used to record eye alignment and
accommodation in infants (Inf) (3 to 5 months; n=17), pre-school
children (PreSch) (2.5 to 5 years; n=19) and uninstructed, naïve
pre-presbyopic adults (Ad) (n=14). Phoria was derived from the
difference between eye alignments measured in monocular and
binocular viewing, while viewing a naturalistic target at 80 cm.
Motor fusion was measured objectively with the photorefractor by
introducing base-in (BI) and base-out (BO) prism (2-40pd). The
prism value at which motor fusion failed was computed .
Results: Mean OD spherical equivalent refraction was +2.4D (SD
±1.2) in infants and +1.1D (± 0.6) in pre-schoolers. The average
phoria was not significantly different (p=0.11) with age (Inf:-0.79
±2.5 pd; PreSch:-2.43±2.0 pd; Ad:-1.0±2.7 pd). Mean vergence
range was also similar between groups for BI (Inf = 11.2±2.5;
PreSch: 8.8±2.8 pd; Ad: 11.8±5.2) and BO prism (Inf, 13.7±0.4pd;
PreSch:15.1±8.3 pd; Ad: 20±9.2pd). Change in accommodation with
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
the highest fusable prism was positive (more accommodation than
naturalistic viewing) with BO (Inf:1.69 ±1.4D; PreSch:1.35±1.6D;
Ad:1.22±1.0D) and negative for BI (Inf:-0.96 ±0.3D; PreSch:0.78±0.6D; Ad:-0.62±0.3D), with similar magnitude across age (BO:
p=0.6; BI: p=0.4).
Conclusions: Despite typical levels of hyperopia, infants and young
children exhibited small exophorias, that were comparable in mean
to adults. Furthermore, participants in all age groups demonstrated
substantial fusional reserves, evidence that the youngest participants
are capable of responding to a large range of disparities.
Accommodation increased wih BO and relaxed with BI by similar
amounts across age. Collectively, these data suggest that motor
performance is compensating for developmental hyperopia and IPD,
in that these characteristics remain consistent with age.
Commercial Relationships: Vidhyapriya Sreenivasan, None; Erin
Babinsky, None; Yifei Wu, None; T R. Candy, None
Support: NIH (R01 EY014460, P30 EY019008) and Fight for Sight
awarded to VS
Program Number: 3996
Presentation Time: 9:15 AM–9:30 AM
Saccadic control in anorexia nervosa
Larry A. Abel1, Andrea Phillipou1, 2, Susan L. Rossell3, 4, David
Castle4, 2, Caroline Gurvich5. 1Optometry & Vision Sciences,
University of Melbourne, Parkville, VIC, Australia; 2The University
of Melbourne, Department of Psychiatry, Parkville, VIC, Australia;
3
Swinburne University of Technology, Brain and Psychological
Sciences Research Centre, Hawthorn, VIC, Australia; 4Psychiatry,
St Vincent’s Hospital, Fitzroy, VIC, Australia; 5Monash Alfred
Psychiatry Research Centre, Melbourne, VIC, Australia.
Purpose: Anorexia Nervosa (AN) is a psychiatric illness
characterised by 3 main criteria: significantly low body weight, a fear
of weight gain and a disturbance in the experience of one’s own body
weight or shape. Neurobiology studies in AN have been inconsistent.
Since the neurobiology of saccades is relatively well understood,
we examined tasks ranging from simple prosaccades to the scanning
of clinically relevant images, as has been done in other psychiatric
disorders.
Methods: 24 AN subjects and 25 age-matched controls (all female)
were studied. Eye movements were recorded at 500 Hz. Prosaccades,
antisaccades and a go/no-go task were interleaved and cued by colour
of the fixation spot. Memory-guided and self-paced saccades were
also studied. During fMRI scanning, subjects viewed emotional
faces and were asked to identify gender, not emotion; an image of
their own face was interleaved. They also viewed biological motion
stimuli showing walkers of both sexes and differing weights, either
identifying sex or estimating weight.
Results: Prosaccade latency was significantly shorter for AN:
206.87±33.72 vs. 250.42±70.97ms, p=.011. Other prosaccade
parameters were normal, as were the antisaccade & go/no-go tasks.
AN participants made significantly more errors on the memoryguided task: 14.81±10.98 vs.8.47±5.32, p=.021. Intersaccadic interval
on the self-paced task fell just short of significance: 164.46±156.12
vs. 401.67±51.28ms, p =.068. For emotional faces AN subjects made
significantly more fixations than controls: 23.67±1.02 vs. 20.42±.99,
p=.027. Their fixation durations were also briefer: 279.06±18.1
vs. 351.65±17.21ms, p=.006. When viewing their own faces, AN
subjects attended salient and non-salient features equally; controls
attended to the salient features (the inner face “triangle”) more. For
biological motion, fixations were again more frequent and briefer for
AN subjects than controls.
Conclusions: Prosaccade generation was intact but initiation was
abnormally short in AN. This and the brief fixations for faces and
biological motion could point to weaker fixation drive but the
hyperscanning on the face and biological motion tasks is consistent
with that seen in anxiety disorders. Their normal antisaccades and
impaired memory-guided saccades differ from results in obsessivecompulsive disorder, with which AN shares some features. This 1st
study of saccades in AN reveals a distinctive pattern of performance.
Commercial Relationships: Larry A. Abel, None; Andrea
Phillipou, None; Susan L. Rossell, None; David Castle, None;
Caroline Gurvich, None
Support: Jack Brockhoff Foundation; Dick and Pip Smith
Foundation
Program Number: 3997
Presentation Time: 9:30 AM–9:45 AM
Visual processing in infantile nystagmus is not slow
Matt J. Dunn, Thomas H. Margrain, Joy Margaret Woodhouse,
Jonathan T. Erichsen. Cardiff University, Cardiff, United Kingdom.
Purpose: Therapeutic interventions aimed at slowing the incessant
eye movements of infantile nystagmus (IN) have elicited subjective
reports of improved visual function, even in cases where visual acuity
was not significantly changed. The purpose of this study was to
investigate the extent to which temporal aspects of vision affect the
visual experience of IN; in particular whether the presumed ‘slow to
see’ phenomenon is primarily due to delays in redirecting the gaze or
an increase in visual processing time.
Methods: The time taken to fixate and respond to the orientation of
peripherally presented Gabor patches was measured in 11 subjects
with IN and 11 controls.
Subjects viewed a fixation cross on a screen at a distance of 2m. After
a random delay of 1-3s, a Gabor patch was presented 3° away from
the primary position in one of four locations (up/down/left/right).
Each Gabor patch was tilted to one of two orientations. As soon as
subjects could locate and identify the targets, a response box was
used to report the direction of tilt. This was repeated until at least 10
presentations in each direction had occurred. Spatial frequency of
the Gabor patch was adjusted relative to each subject’s visual acuity
in order to make the task equally difficult for all subjects. For targets
presented either above or below the primary position, the time from
presentation until the target acquiring saccade, and the time from
the end of the saccade until the response was calculated. Due to
the presence of horizontal nystagmus, it was not possible to detect
the time to fixation for targets presented left or right of the primary
position.
Results: For vertically displaced targets, subjects with IN took
significantly longer than controls to redirect their gaze towards the
targets (IN: 0.25s [IQR 0.23 – 0.39s], controls: 0.19s [IQR 0.18
– 0.21s], P < 0.01). However, there was no significant difference
between subject groups in the time between saccade termination and
subject response (IN: 0.59 s [IQR 0.48 – 0.84s], controls: 0.63s [IQR
0.59 – 0.65s], P = 0.78).
Conclusions: The results of this study suggest that IN does not affect
the time taken to process visual information; once a target has been
foveated, it is processed at a ‘normal’ speed. This study furthers our
understanding of the visual difficulties associated with the condition,
showing that the ‘slow to see’ phenomenon arises as a result of
delayed targeting saccades, rather than slowed visual processing.
Commercial Relationships: Matt J. Dunn, None; Thomas H.
Margrain, None; Joy Margaret Woodhouse, None; Jonathan T.
Erichsen, None
Support: Nystagmus Network, College of Optometrists
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 3998
Presentation Time: 9:45 AM–10:00 AM
Examination of Extraocular Muscles and Their Innervation from
Subjects with Infantile Nystagmus Syndrome and Optic Nerve
Hypoplasia
Linda K. McLoon1, Matthew D. Kunz1, Joost Felius2, David Stager2,
Jill S. Anderson1, Erick D. Bothun1. 1University of Minnesota,
Minneapolis, MN; 2Retina Foundation of the Southwest, Dallas, TX.
Purpose: Infantile nystagmus syndrome (INS) is an eye motility
disorder characterized by involuntary conjugate oscillatory eye
movements. INS is often associated with structural abnormalities
in the afferent visual pathways. Our previous work suggested that
the idiopathic form of INS and INS associated with albinism may
be related to dysregulation of innervation. INS may also occur
in conjunction with optic nerve hypoplasia (ONH). Our working
hypothesis is that the extraocular muscles (EOM) from INS patients
with ONH will have innervational adaptations that may provide
insight into possible mechanisms that cause INS.
Methods: We have examined EOM specimens removed as part of
the normal surgical treatment of 2 patients with INS and ONH (age
6 and 10 years) compared to 3 age matched normal controls and
3 age matched subjects with idiopathic INS. They were examined
for neuromuscular junction density and neuromuscular junction
morphology. All studies were approved by the IRB at the University
of Minnesota.
Results: The EOM from the subjects with INS and ONH showed
a number of features suggestive of innervational dysregulation.
Neuromuscular junctions were almost 50% smaller than in control
EOM, but resembled the smaller neuromuscular junctions of the
idiopathic INS and INS/albinism EOM. Additionally, there was an
increase in the density of slow myofibers, at 28% of total myofibers,
compared to idiopathic INS and normal controls, at 22% and
16% respectively. Most striking was the presence of the immature
gamma subunit of the acetylcholine receptor on fast myofibers in
the neuromuscular junctions from the muscles obtained from INS
patients with ONH, at almost 100%, compared to EOM from patients
with idiopathic INS and to controls, where this occurred only rarely.
Conclusions: Similar to our previous results for muscles from
subjects with INS and albinism, it appears that the EOM in patients
with INS and ONH have changes suggestive of a dysinnervation
syndrome. This includes increased density of neuromuscular
junctions which are reduced in size, as well as retention of the gamma
subunit on fast myosin-expressing myofibers. These results suggest
potential new approaches that focus on neuromuscular junction
maturation that might be used to alleviate the abnormal oscillatory
movements associated with INS.
Commercial Relationships: Linda K. McLoon, None; Matthew
D. Kunz, None; Joost Felius, None; David Stager, None; Jill S.
Anderson, None; Erick D. Bothun, None
Support: NIH RO1EY015313, NIH P30EY11375, Minnesota Lions
and Lionesses, Research to Prevent Blindness, Inc.
Program Number: 3999
Presentation Time: 10:00 AM–10:15 AM
Clinical Contrast Sensitivity (CS) Testing in Patients with
Infantile Nystagmus Syndrome (INS) Before and After Eye
Muscle Surgery
Richard W. Hertle, megan cochran. Ophthalmology, Children’s Hosp
Medical Ctr of Akron, Akron, OH.
Purpose: The purpose of this report is to characterize the change
in contrast sensitivity using a commercially available technique in
patients with INS before and after eye muscle surgery.
Methods: This is a prospective, case series using the CSV-1000ER
(VectorVision) contrast sensitivity (CS) test performed binocularly,
with best corrected acuity, under office lighting (~85.0 candelas [cd]
m2), before and 6 weeks after eye muscle surgery for nystagmus.
The CS values are documented in log units. Sensitivity levels at each
frequency ranged from 0.70 to 2.08 (3 cpd), 0.91 to 2.29 (6 cpd),
0.61 to 1.99 (12 cpd), 0.17 to 1.55 (18 cpd) log units. The Friedman
test was used to evaluate the differences in the CS before and after
surgery. The correlation between the absolute change in CS against
the change in visual acuity was also evaluated using the Spearman
correlation coefficient (r).
Results: 25 patients with INS patients aged 12-55 years are included
in this report. The INS patients’ best binocular acuity ranged from
20/125 to 20/30. Associated sensory system deficits included
albinism, strabismus, amblyopia, and optic nerve dysplasia and
retinal dystrophy. There was a statistically significant increase in
CS at 6 weeks after surgery (P< .0012). There was no correlation
between in visual acuity changes after surgery and the improvement
in CS (r=.49, P=.10).
Conclusions: INS patients with or without sensory system deficits
display deficiencies in CS function which improves after eye muscle
surgery independent of changes in high spatial frequency acuity.
Enhanced CS may explain the subjective improvement in vision
patients report after eye muscle surgery for nystagmus. CS may have
potential as a primary clinical outcome measure in interventional
trials in patients with INS.
Commercial Relationships: Richard W. Hertle, None; megan
cochran, None
Support: The Rebecca Considine Research Institute, Akron
Children’s Hospital, Akron Ohio
445 Oculoplastics
Wednesday, May 06, 2015 11:00 AM–12:45 PM
Exhibit Hall Poster Session
Program #/Board # Range: 4733–4763/D0178–D0208
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Program Number: 4733 Poster Board Number: D0178
Presentation Time: 11:00 AM–12:45 PM
Current Anesthetic Practices Among Oculoplastic Surgeons
Anna Berry1, Jason Sokol1, Peter Timoney2. 1Ophthalmology,
University of Kansas Medical Center, Prairie Village, KS;
2
Ophthalmology, University of Kentucky, Lexington, KY.
Purpose: To evaluate the practice of and influencing factors on the
choice of anesthesia for various orbital surgeries by Oculoplastic
surgeons.
Methods: An IRB exempt anonymous survey using REDCap
electronic capture tools hosted at University of Kansas Medical
Center was sent via email to the American Society of Ophthalmic
Plastic & Reconstructive Surgery (ASPORS) members. The survey
contained two parts for each surgical procedure: anesthetic preference
and primary influencing factor. Demographics including number of
years in practice and practice type were also collected. Responses
were analyzed using standard statistical methods.
Results: One hundred and eighteen ASOPRS members responded
to the survey during a two-week period for a response rate of 23.6%.
General anesthesia was the anesthetic method of choice for eight
of the nine surgical procedures: enucleation (88.1%), evisceration
(74.6%), external dacryocystorhinostomy (DCR) (54.2%),
endoscopic DCR (55.1%), endoscopic brow lift (37.3%), external
ethmoidectomy (49.2%), orbital floor decompression (95.8%), and
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
lateral wall orbital decompression (94.1%). Monitored anesthesia
care (MAC) was the anesthetic of choice for open brow lift (68.6%).
“Current facility practices” was the primary factor for anesthetic
choice with endoscopic DCR (30.0%), open brow lift (32.2%), and
endoscopic brow lift (32.2%). “Fellowship training” was the primary
choice with orbital floor decompression (45.8%) and lateral wall
orbital decompression (44.9%). The category “other” was the primary
factor for enucleation (50.9%), evisceration (50.9%), external DCR
(42.4%) and external ethmoidectomy (20.3%). Patient comfort was
the most frequent response for “other” for each surgical procedure.
Conclusions: General anesthesia is the most common anesthetic
method used but the underlying reasoning for the choice varied by
surgical procedure. The most agreement by ASOPRS members on
anesthetic choice was found, in descending order, for orbital floor
decompression, lateral wall orbital decompression, enucleation, and
evisceration.
Methods: We performed a prospective, non-randomized assessment
of 55 patients. 30 were undergoing eyelid surgery under local
anesthesia (LA) and 25 were undergoing squint surgery under general
anesthesia (GA). All the patients were treated in similar conditions.
Anxiety was evaluated pre-operatively by the French version of the
APAIS. This scale is composed of 6 simple questions: 2 evaluate the
anxiety regarding anesthesia, 2 concern anxiety about the surgery and
2 questions evaluate the need for information about the surgery and
anesthesia. Each question is rated on a severity scale of 1 to 5. For
each patient a global APAIS score, considering all parameters was
calculated. Individual anesthesia, surgery and need for information
APAIS scores were also calculated. The APAIS scores were collected
and tabulated. The data was analyzed with nonparametric Mann
Whitney U, ANOVA, Tukey’s and Bartlett’s tests. P<0.05 was
considered significant
Results: Of the 55 patients studied, 24 were female. the mean age
was 54 years. The global anxiety scale was not significantly different
between male and female patients (P=0.09). Also, there was no
significant difference in global and surgery APAIS scores between the
oculoplastic and strabismus surgery groups (P=0.38). Likewise, the
need for information was similar in both groups of patients. However,
there was significant difference in APAIS scores between GA and LA
groups, the GA group, having higher APAIS scores (P=0.002)
Conclusions: The APAIS assessment scale revealed similar anxiety
levels and need for information in both oculoplastic and strabismus
procedures. Higher anxiety levels were found for GA than LA. This
study has clinical implications as results of pre-operative anxiety
assessment can assist with operative and post-operative patient
management. This is the first study using the APAIS scale for
pre-operative evaluation of anxiety in oculoplastic and strabismus
surgeries
Percentage of anesthetic choice per procedure.
*Margin of Error
Commercial Relationships: Anna Berry, None; Jason Sokol,
None; Peter Timoney, None
Program Number: 4734 Poster Board Number: D0179
Presentation Time: 11:00 AM–12:45 PM
EVALUATION OF PREOPERATIVE ANXIETY IN PATIENTS
UNDERGOING OCULOPLASTIC AND STRABISMUS
SURGERY; A PROSPECTIVE STUDY
Camille Bosc5, JOYCE MBEKEANI2, 3, franck jaspart1, HELENE
DALENS5, Frederic Chiambaretta5, Hachemi Nezzar5, 4. 1CHU
Clermont Ferrand, Clermont Frrand, France; 2Dept of Surgery,.
North Bronx Health Network, Bronx, NY, New York, NY; 3Dept
of Ophthalmology and Visual Science, Albert Einstein College of
Medicine,, new York, NY; 4OPHTHALMOLOGY, KING FAISAL
SPECIALIST HOSPITAL & RESEARCH CENTER, Riyadh, Saudi
Arabia; 5ophtalmologie, CHU Clermont Ferrand, Clermont Ferrand,
France.
Purpose: Preoperative anxiety is well known to influence response to
anesthesia and analgesic consumption
The Amsterdam Preoperative Anxiety and Information Scale (APAIS)
has been utilized in various surgical scenarios and found to have
validity in evaluating preoperative anxiety. The purpose of this study
is to evaluate the preoperative anxiety in adult patients undergoing
oculoplastic and squint surgeries using the APAIS scale. To date no
such study has been conducted
Commercial Relationships: Camille Bosc, None; JOYCE
MBEKEANI, None; franck jaspart, None; HELENE DALENS,
None; Frederic Chiambaretta, None; Hachemi Nezzar, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 4735 Poster Board Number: D0180
Presentation Time: 11:00 AM–12:45 PM
Aesthetic benefits of CO2 laser photorejuvenation treatment for
malar mounds (festoons)
Juan C. Jimenez1, Jose R. Montes1, Joseph Maldonado2.
1
Ophthalmology, UPR Medical Sciences Campus, San Juan; 2School
of Medicine, UPR Medical Sciences Campus, San Juan.
Purpose: To review the effectiveness of CO2 laser for malar mounds
in patients undergoing lower eyelid blepharoplasty.
Methods: Retrospective medical chart review of patients that
had lower eyelid blepharoplasty and received CO2 laser in an
oculoplastic practice during the past 3 years. Outcome measures
were improvement or resolution of malar mounds after CO2 laser
treatment. Inclusion criteria were malar mounds in addition to
periocular fat herniation. Exclusion criteria were any patient that has
had lower lid blepharoplasty in the past. Age, sex, smoking status,
medical history, type of skin (Fitzpatrick scale), degree of skin
thickness and laser parameter were recorded. Pre and post operative
pictures were compared by three independent observers to determine
if CO2 laser was effective as a treatment for malar mounds.
Results: Six patients (2 men and 4 women) with a mean age of 71
years old + 10 (standard deviation; range of 57 - 86 years old) that
met the inclusion criteria underwent treatment with partial festoon
resolution in 2 (33%) and complete festoon resolution in 4 (66%).
Three (50%) patients had skin type IV, 2 (33%) had skin type III-IV
and 1 (17%) had skin type IV-V. Four (66%) patients had medium
skin thickness, 1 (17%) had large skin thickness and 1 (17%) had
fine to medium skin thickness. Complications were scleral show in 3
(50%), hyperemia in 6 (100%) and hyperpigmentation in 1 (17%).
Conclusions: CO2 laser ablation is an effective and safe procedure
for treatment of malar mounds. Ideal patients are those with fine to
medium skin thickness and mild to moderate edema. The darker the
skin the higher the risk for post inflammatory hyperpigmentation
which is a common adverse event that can be prevented or treated
with topical agents such as Hydroquinone 4% and anti-inflammatory
drugs. Other adverse events such as erythema and scleral show are
common and usually self limiting.
Commercial Relationships: Juan C. Jimenez, None; Jose R.
Montes, None; Joseph Maldonado, None
Program Number: 4736 Poster Board Number: D0181
Presentation Time: 11:00 AM–12:45 PM
Ablative fractional laser resurfacing with laser-assisted delivery
of 5-fluorouracil: a novel non-surgical treatment for cicatricial
ectropion
Alexandra E. Levitt1, Bradford Lee2, Audrey C. Ko1, Wendy W. Lee1.
1
Bascom Palmer Eye Institute, Miami, FL; 2Shiley Eye Center, San
Diego, CA.
Purpose: Periocular scarring can cause significant functional and
cosmetic distortions of the eyelid. Surgical treatments for cicatricial
ectropion (CE) using full-thickness skin grafting are associated with
complications such as recicatrization, donor site morbidity, and
textural and pigmentary abnormalities. This case series reports on the
efficacy and safety of a novel non-surgical approach to treating CE
using ablative fractional laser resurfacing (AFLR) and laser-assisted
delivery of 5-fluorouracil (LA 5-FU).
Methods: The records of three patients with CE who were treated
with AFLR and LA 5-FU were retrospectively studied. All patients
received at least 3 rounds of AFLR with Erbium:YAG 2940nm,
YSGG 2790nm, or CO2 10600nm lasers with the additional use
of topically applied LA 5-FU immediately following treatment.
Functional and cosmetic outcomes were evaluated via fluorescein and
lissamine green staining of the ocular surface, Ocular Surface Disease
Index questionnaire (OSDI), Patient and Observer Scar Assessment
Scale (POSAS), a questionnaire on patient satisfaction with scar
appearance, and clinical photographs documenting the external exam.
Results: Case 1 presented with CE, lagophthalmos, severe
pigmentary and textural skin abnormalities, and exposure keratopathy
secondary to facial burns, and underwent 4 AFLR treatments along
with LA 5-FU. Following treatment, he had complete resolution
of lagophthalmos, CE, brow elevation, and keratopathy (Figure 1).
Cases 2 and 3 presented with CE and eyelid retraction following
Mohs reconstructions and received 3 treatments of AFLR with LA
5-FU. Both saw improvement in fluorescein staining. Case 2 had
complete resolution of CE, symptomatic improvement of dry eye
syndrome (reduction of OSDI) and reduced lissamine green staining.
Case 3 had partial improvement of CE but ultimately opted for skin
grafting. All patients had marked improvement in scar elevation
and textural and pigmentary abnormalities and high self-reported
satisfaction with treatment. No adverse events were reported.
Conclusions: AFLR with LA 5-FU appears to be a safe and effective
treatment for CE with the additional benefit of improving scar
elevation, skin texture and pigmentary abnormalities, all of which
cannot be addressed by surgical interventions.
Commercial Relationships: Alexandra E. Levitt, None; Bradford
Lee, None; Audrey C. Ko, None; Wendy W. Lee, Cutera (C),
Lumenis (C)
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 4737 Poster Board Number: D0182
Presentation Time: 11:00 AM–12:45 PM
Anatomical Relationships of Hyaluronic Acid Gel Following
Injection to the Temporal Fossa
Rao Chundury1, Adam Weber1, Nathaniel Sears1, Jennifer McBride3,
Thomas Plesec2, Julian D. Perry1. 1Cole Eye Institute, Cleveland
Clinic Foundation, Cleveland, OH; 2Anatomic Pathology, Cleveland
Clinic Foundation, Cleveland, OH; 3Lerner College of Medicine,
Cleveland Clinic Foundation, Cleveland, OH.
Purpose: With age, the subcutaneous fat, temporalis muscle and
temporal bones are thought to thin resulting in temporal hollowing. A
restorative and more youthful appearance can be accomplished using
hyaluronic acid (HA) filler rejuvenation. Hyaluronic acid fillers have
been commonly used to address temporal fossa hollows by injecting
either deep to the temporalis muscle or subcutaneously. However,
there have been case reports of vascular injury when injecting within
this area. This study aims to investigate the histologic location of HA
gel following subcutaneous injection for temporal fossa hollows in
cadaver specimens.
Methods: Bilateral temporal fossas of 3 fresh cadaver specimens (6
samples) were dissected following subcutaneous injection of HA,
Belotero Balance (Merz Aesthetics, Inc., Greensboro, NC, USA).
Each injection was delivered in a fan and cross-hatch pattern directly
within a subcutaneous injection plane (Figure 1). Conservative
post-injection molding to the smooth the contour was performed
on each specimen similar to that used in a clinical setting. The soft
tissue specimens were grossly dissected to the supraperiosteal plane.
The specimens were fixed, stained with H&E and then histologically
examined.
Results: Hyaluronic acid was directly visualized in all specimens
as shown in Figure 2. The majority (95%) of HA was noted to
be deposited in subcutaneous fat in all but one specimen. In one
specimen HA was noted to be in close proximity to a muscular artery
(Figure 2).
Conclusions: This study presents the first histoanatomical view of
the position of HA following subcutaneous injection of the temporal
fossa. Subcutaneous injection of filler in the temporal region may
pose risk for inadvertent intravascular injection due to the proximity
of the superficial temporal fascia and associated temporal vessels.
Care should be taken to superficially inject filler when injecting
subcutaneously for temporal hollows.
Figure 1: External photograph of cadaver demonstrates temporal
fossa dissection borders post-HA injection and molding
Figure 2: Low power photomicrograph of hemotoxylin- and
eosin-stained temporal fossa sample showing HA filler within the
subcutaneous fat (black arrows) and surrounding a muscular artery
(blue arrow). 18x magnification
Commercial Relationships: Rao Chundury, None; Adam Weber,
None; Nathaniel Sears, None; Jennifer McBride, None; Thomas
Plesec, None; Julian D. Perry, None
Support: Cleveland Clinic Foundation Travel Subsidy
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 4738 Poster Board Number: D0183
Presentation Time: 11:00 AM–12:45 PM
Google Glass in Oculoplastic Surgery: measurement of the
margin reflex distance
Rohini Rao, Catherine Choi, Michael K. Yoon. Ophthalmology,
Massachusetts Eye & Ear Infirmary, Boston, MA.
Purpose: Google Glass is a commercially available wearable
technology consisting of a camera, optical display, microphone,
touchpad, accelerometer, gyroscope, and bone-conduction speaker. It
is relatively new to the market, and its application in healthcare has
been rapidly expanding.1,2 Amongst its use in oculoplastic surgery
is documentation of eyelid position. The margin reflex distance-1
(MRD-1) is the distance between the corneal light reflex and the
upper eyelid margin in primary gaze. We have demonstrated the use
digital photography with a handheld camera in image measurements
of eyelid position. In the present study, we explore whether Google
Glass can also be used for digital photography analysis of eyelid
position. This proof of concept study compared clinically measured
MRD-1 and Google Glass photographs.
1. Emergency providers see big potential for Google Glass. ED
Manag. 2014;5(26):55-8.
2. Kantor J. First look: google glass in dermatology, mohs surgery,
and surgical reconstruction. JAMA dermatology 2014;150(11):1191.
Methods: 11 healthy patients (22 eyes) without ophthalmic disease
were examined and photographed. The MRD-1 was measured with a
handheld ruler. Google Glass photographs were taken of each subject
with a ruler placed on the forehead in plane with the corneal surface.
Digital image analysis of the photographs was performed to obtain
the MRD-1 with ImageJ (http://rsbweb.nih.gov/ij). Unpaired t-test
was used to compare the clinical measurement to the image analysis
(www.graphpad.com/quickcalcs/ttest1.cfm).
Results: There were 10 women and 1 man. Mean clinical MRD-1
was 4.16 (range 3.0 to 6.0). The mean digital MRD-1 was 4.30 (range
3.08 to 5.78). Unpaired t-test revealed no statistically significant
difference between these two groups (P = 0.56).
Conclusions: Google Glass offers the ability to analyze photographs
for clinically relevant measurements. Our analysis demonstrates
that these measurements were not statistically different from clinical
evaluation. There were limitations to using this device, including
camera positioning. However, this proof of concept study opens
the possibility to modifications to the hardware and/or software of
Google Glass to refine the photographic ease of use and resolution.
Commercial Relationships: Rohini Rao, None; Catherine Choi,
None; Michael K. Yoon, None
Program Number: 4739 Poster Board Number: D0184
Presentation Time: 11:00 AM–12:45 PM
Effect of Upgaze on Lower Eyelid Position in Congenital Ptosis
Livia Teo1, 2, Chang Yeom Kim2, Sang Yeul Lee2. 1Oculoplastics,
Singapore National Eye Centre, Singapore, Singapore;
2
Oculoplastics, Institute of Vision Research, Department of
Ophthalmology, Yonsei University College of Medicine, Seoul,
Korea (the Republic of).
Purpose: The purpose of this study was to determine the effect
of upgaze on lower eyelid position in patients with unilateral and
bilateral congenital ptosis.
Methods: Thirty- five patients were recruited for this study. Clinical
photographs and measurements were taken in primary gaze and
upgaze. An 8-millimeter circular disc was placed on the child’s
forehead as a measuring guide. Measurements taken from photograph
and clinical records include inferior scleral show (ISS), vertical lower
lid height (LL) and canthal tilt angle (CTA).
Results: There were 35 patients with congenital ptosis. 62.9%
(n=22) of them were male. The mean age of the patients was 4.38
± 1.81 years. 62.9% (n=22) of the patients had unilateral ptosis and
37.1% (n=13) had bilateral ptosis. There was more ISS in unilateral
ptosis eyes compared to the normal side in both primary gaze (0.3±
0.5mm; 0.1± 0.2mm) (p<0.05), as well as in upgaze (3.3± 1.3mm;
2.1± 1.3mm) (P< 0.01); with corresponding increase in ISS on
upgaze (p<0.05). There was also more ISS in unilateral ptosis eyes as
compared to bilateral ptosis eyes in primary gaze (0.3 ± 0.5mm; 0.1±
0.2mm) (p<0.05) as well as in upgaze (3.3± 1.3; 1.6± 1.3)(P<0.01);
with accompanying increase in ISS on upgaze (P<0.01). There was
less elevation of the lower lid in ptosis eyes (0.5± 0.7mm) versus
normal eyes (0.8± 0.7mm) but this was not statistically significant
(p=0.07). CTA was lower in ptosis eyes compared to normal eyes
in primary gaze (2.8± 3.5°; 5.2± 3.4°) (p<0.01) as well as in upgaze
(0.7± 3.9°; 3.2± 4.6°)(p<0.05).
Conclusions: Upgaze appears to increase inferior scleral show in
children with congenital ptosis. We propose that the contraction of
the superior complex to allow foveation results in compensatory
inferior rectus contraction and a tightening of Lockwood ligament
with superior globe displacement. There is underdevelopment
of the levator muscle in congenital ptosis, which results in less
compensatory contraction of the lower eyelid retractor and less
elevation of the lower lid in ptosis eyes. Canthal tilt is lower in
congenital ptosis than in normal eyes on primary gaze and upgaze.
The weaker levator muscle is unable to counteract this, hence
resulting in greater downward angulation at the lateral canthus (the
fulcrum). It is important to understand the vectors of movement, as
patients need to be counseled for possible cosmetic asymmetry on
upgaze.
Commercial Relationships: Livia Teo, None; Chang Yeom Kim,
None; Sang Yeul Lee, None
Program Number: 4740 Poster Board Number: D0185
Presentation Time: 11:00 AM–12:45 PM
Frontalis muscle flap transposition as a novel technique for
lateral eyebrow ptosis repair
Preethi S. Ganapathy, Rao Chundury, Julian Perry. Cleveland Clinic
Cole Eye Institute, Cleveland, OH.
Purpose: Eyebrow ptosis is a significant aesthetical and functional
age-related change of the upper face. We previously described
anatomic variation in frontalis muscle landmarks in elderly Caucasian
cadavers that may account for the pathogenesis of lateral brow ptosis;
we subsequently developed a novel, minimally invasive technique
to transpose a flap of lateral frontalis muscle to improve lateral brow
elevation. In this study, we tested the hypothesis that the frontalis
muscle flap transposition (FMFT) procedure would significantly
elevate the lateral brow and substantially improve lateral eyebrow
ptosis.
Methods: The charts of patients who underwent FMFT from
December 2013 through September 2014 were reviewed. In brief,
a 1.5cm ellipse of skin and subcutaneous tissue was first excised in
the region of a lateral forehead rhytid. Blunt dissection exposed the
lateral frontalis muscle and a pedicle flap was created, trimmed, and
transposed laterally in a graded approach to achieve optimal eyebrow
height and contour. The incision was closed with 5-0 polypropylene
suture. Pre- and post-operative photos were taken of each patient, and
the following parameters assessed using Image J (provided by the
National Institutes of Health): corneal diameter (CD), margin reflex
distance (MRD1), central brow height (CBH), medial brow height
(MBH), lateral brow height (LBH), and central pupillary brow height
(CPBH). Measurements were normalized to CD, and an average
CD of 11.5mm was used to calculate millimeters of brow height
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
elevation. Statistical analysis was performed using the Student’s t-test
with p<0.05 considered significant.
Results: 32 total patients were analyzed; of these 27 underwent
FMFT + blepharoplasty and 5 underwent FMFT alone. In the
combined procedure group, there was significant increase in LBH by
1.8mm (p<0.05), CPBH by 1.76mm (p<0.05), and MRD1 by 0.91mm
(p<0.01). In brows that underwent FMFT alone, there was a greater
significant increase in LBH by 4.1mm (p<0.05), CPBH by 3.32mm
(p<0.05), and no significant change in MRD1.
Conclusions: We have shown that FMFT alone results in substantial
lateral brow elevation. In combination with blepharoplasty, this
technique provides a less robust, yet still significant elevation in
LBH. This study provides the first objective outcome measures for
FMFT as a novel and effective technique for lateral eyebrow ptosis
repair through a small concealed incision.
Commercial Relationships: Preethi S. Ganapathy, None; Rao
Chundury, None; Julian Perry, None
Program Number: 4741 Poster Board Number: D0186
Presentation Time: 11:00 AM–12:45 PM
Frontalis Suspension for Congenital Ptosis: Evaluation of Suture
Material in Pediatric Patients
Cajal Patel1, 2, Chrysavgi Adamopoulou2, Leemor Rotberg2.
1
Ophthalmology, Wayne State University, Detroit, MI; 2Children’s
Hospital of Michigan, Detroit, MI.
Purpose: Congenital ptosis is caused by myogenic dysgenesis, which
can cause deprivation or refractive amblyopia in young patients. To
compensate, they often adopt an anomalous head position, which can
limit mobility and cause neck strain. For patients with poor levator
function, the ptosis is typically managed by frontalis sling to correct
the head position and manage or prevent amblyopia. Several studies
have evaluated the outcomes of this procedure. However, patients
with ptosis of any etiology as well as of all ages were included in
those studies. We assessed the surgical outcomes of pediatric patients
undergoing frontalis sling strictly for congenital ptosis without a
previous history of eyelid surgery. We hypothesized that recurrence
rates would vary depending on the material used.
Methods: The charts of 39 patients with congenital ptosis who
underwent frontalis sling were retrospectively reviewed. All surgeries
were performed by the same surgeon and the same surgical technique
was used in all patients. Forty-nine (n=49) eyes were included in
the study. Patients with previous lid surgery or ptosis of an etiology
other than congenital were excluded. The mean age of patients was
9.5 months. Data collected at the time of surgery included age,
visual acuity, refractive error, margin to light reflex distance(MRD1),
levator function, suture material, as well as the presence of
amblyopia, strabismus or chin up position. MRD 1 was also recorded
in all post-operative visits as well as the time to recurrence. The
average follow-up was 18.1 months for those who did not develop
recurrence. Suture material used included ptose-up, (N=17),supramid
(N=28) and silicone rods (N=4) .
Results: No statistical significance was found in the rate of
recurrence between the two materials.
Conclusions: Evaluation of a larger sample size may help determine
if suture material has any bearing on surgical outcome, recurrence
and complication rate, which may help guide surgical practice in the
management of congenital ptosis.
Commercial Relationships: Cajal Patel, None; Chrysavgi
Adamopoulou, None; Leemor Rotberg, None
Program Number: 4742 Poster Board Number: D0187
Presentation Time: 11:00 AM–12:45 PM
Total Upper Eyelid Reconstruction with Modified Cutler-Beard
Procedure Using Autogenous Auricular Cartilage
Shilpa G. Reddy1, James C. Fleming1, Brian Fowler1, Salil K.
Mandal2. 1Ophthalmology, University of Tennessee, Memphis, TN;
2
Medical College of Calcutta, Calcutta, India.
Purpose: In this study, we aim to evaluate the efficacy of the
modified Cutler-Beard procedure using autogenous ear cartilage for
tarsal plate reconstruction in the repair of upper eyelid defects greater
than 70%, as the procedure is traditionally used only for lid large lid
defects up to 70%. In addition, we aim to discuss cost and safety of
using autogenous ear cartilage rather than other alternatives, such as
synthetic graft tissue and allografts, for tarsal plate reconstruction.
Methods: This is a retrospective, interventional case series of eight
patients over a period of three years. All patients had malignant
tumors of the upper lid requiring removal of 70-100% of the upper
eyelid. All patients’ lid defects were repaired using a modified
Cutler-Beard procedure, utilizing autogenous auricular cartilage for
stability of the lid that the tarsal plate normally imparts. Patient were
followed over a period of six months to one year with postoperative
ophthalmologic examinations and photos at each visit.
Results: Upper eyelid recreation was successful in all cases without
complications. The autogenous auricular cartilage graft maintined
excellent architecture and motility in all patients at follow-up visits,
resulting in good cosmetic result and functionality.
Conclusions: The modified Cutler-Beard procedure using an
autogenous auricular cartilage graft is an effective procedure for
repair of eyelid defects greater than 70%, with good functional and
cosmetic results. Moreover, it is particularly useful in resource-poor
areas, due to lower cost than other available options, such as the use
of synthetic graft tissue and allograft materials.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Patient with sebaceous cell carcinoma, which was excised. Modified
Cutler-Beard procedure was then used to repair the lid defect.
margin distances were calculated in pixels by digitally rendering
vertical lines 15 degrees apart (00, 150, 30°, 45°, 60°, 75°, 90°, 105°,
120°, 135°, 150° and 1800) using NIH ImageJ64 software (Bethesda,
MD). Eyelid contour was computed and evaluated as the ratios of
equidistant angles from the midline similar to a previously published
study (for example: 105°/75°). A ratio of 1 represents favorable
contour. Student’s t-tests were used to compare the pre-operative and
post-operative contour ratios to the fellow non-operative eye.
Results: Eight patients met inclusion criteria. Central eyelid elevated
by a mean of 285.92% post-ELR. The mean lateral/medial ratios at
each angle pre and post-ELR and in the fellow non-operative eye are
listed in Table 1. The four central post-ELR lateral/medial ratios were
significantly more symmetric than the fellow non-operative eye as
shown in Table 2.
Conclusions: Eyelid contour changes significantly following external
levator resection for blepharoptosis. In this study, pre and post-ELR
equidistance angle ratios were analyzed and compared to a fellow
non-operative eye. The ELR procedure was found to result in a
significantly improved eyelid contour when compared to the fellow
non-operative eye.
Table 1: Radial mid-pupil distance ratios
Table 2: p-value: Comparing pre-ELR and post-ELR to fellow nonoperative eye
Commercial Relationships: Maria M. Choudhary, None; Rao
Chundury, None; Tal Rubinstein, None; Julian Perry, None
Another patient, with good lid opening after large eyelid defect
repaired with modified Cutler-Beard procedure.
Commercial Relationships: Shilpa G. Reddy, None; James C.
Fleming, None; Brian Fowler, None; Salil K. Mandal, None
Program Number: 4743 Poster Board Number: D0188
Presentation Time: 11:00 AM–12:45 PM
Effect of External Levator Resection for Blepharoptosis Repair
on Eyelid Contour
Maria M. Choudhary, Rao Chundury, Tal Rubinstein, Julian Perry.
Cole Eye Institute, Cleveland, OH.
Purpose: Eyelid contour is important for eyelid symmetry and
represents an important clinical outcome after blepharoptosis repair.
We sought to quantitatively determine the effect of external levator
resection for blepharoptosis repair on upper eyelid contour.
Methods: After obtaining Institutional Review Board (IRB)
approval we retrospectively reviewed charts of consecutive
patients undergoing unilateral external levator resection (ELR) for
blepharoptosis repair at the Cole Eye Institute between June 2012 and
October 2013. Exclusion criteria included concurrent or prior eyelid
or eyebrow surgery, lack of appropriate photographs, and a known
history of systemic disease affecting the eyelid.
Preoperative and postoperative digital images of the palpebral fissure
in primary gaze of patients were analyzed. Radial mid-pupil to eyelid
Program Number: 4744 Poster Board Number: D0189
Presentation Time: 11:00 AM–12:45 PM
Conjunctiva Muller Muscle Resection Belpharoptosis Repair:
Efficient, Reliable and Predictable
sara khandan1, John Koh2, 1. 1Ophthalmology, William Beaumont
Hospital, Troy, MI; 2Ophthalmology, Wayne State University, Detroit,
MI.
Purpose: To demonstrate predictability and outcomes with
conjunctiva Muller muscle resection (CMR) for blepharoptosis repair
using a new algorithm.
Methods: Retrospective review of 105 patients and 182 eyelids that
underwent CMR at one site with a single surgeon. 77 women and 28
men aged between 25-90 years old. Measured endpoints included
pre and post-operative MRD1, symmetry, complication rates and
symptomatic dry eye post-operatively. Patients were followed for a
12 month post-operative period.
Results: Pre-operative MRD1 ranged between -3 to +3 mm with a
mean of 0.6 mm. Post-operative MRD1 ranged between 1 to 4.5 mm
with a mean of 2.6 mm. 95.1% of patients had symmetry up to 1 mm
and 89% up to 0.5 mm. 17.6% patients were undercorrected. 11.5%
of patients were overcorrected. 1% of patients sustained a corneal
abrasion post-operatively. Patients with glaucoma filtering blebs had
no post-operative complications.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Conclusions: Using a new algorithm, this modified CMR technique
is highly reliable and predictable. It is an effective treatment for mild
to severe ptosis; it does not worsen dry eye symptoms; and it can
be using safely in the presence of glaucoma filtering blebs. Other
advantages of CMR include preservation of natural eyelid contour
and the ability to perform this procedure under general anesthesia.
Commercial Relationships: sara khandan, None; John Koh, None
Program Number: 4745 Poster Board Number: D0190
Presentation Time: 11:00 AM–12:45 PM
A Retrospective Study Comparing Lateral Tarsal Strip with
Everting Sutures to Two Other Surgical Methods for Lower Lid
Involutional Entropion Repair
Ru-ik Chee1, Gary J. Lelli1, Benjamin M. Levine1, Lorraine Cassidy2.
1
Ophthalmology, Weill Cornell Medical College, New York, NY;
2
Ophthalmology, Trinity College Dublin, Dublin, Ireland.
Purpose: The Lateral Tarsal Strip with Everting Sutures (LTSES) procedure has been described as a simple effective surgery for
involutional entropion. We performed a retrospective, observational
clinical study to evaluate the outcomes of LTS-ES and two other
surgical methods in the management of lower lid involutional
entropion.
Methods: We reviewed all surgeries performed for lower lid
involutional entropion at the Royal Victoria Eye and Ear Hospital,
Ireland, from January 2004 through December 2009. Patients were
excluded if they had 1) less than 12 months of follow-up; 2) prior lid
surgery, enucleation or trauma; 3) facial nerve palsy; 4) isolated use
of everting sutures; 5) other causes of entropion such as cicatricial or
congenital. Outcomes included any suboptimal result (recurrence of
entropion, overcorrected ectropion, wound dehiscence), and need for
re-operations. Student’s t, Chi-square, and Fischer’s exact tests were
used in statistical analysis.
Results: A total of 189 eyes from 164 patients were included.
The most common procedure performed was LTS+ES (118 eyes,
62.4%), followed by Wies (43 eyes, 22.8%) and Wies with lateral
full thickness wedge resection (Wies-R) (28 eyes, 23.7%). Mean age
(77.2 vs. 80.2 years, p=0.1039), gender (59.3% vs. 46.5% males,
p=0.1173), and follow up duration (16.3 vs. 19.9 months, p=0.944)
were not significantly different between LTS-ES and non-LTS-ES
groups. Suboptimal results were significantly lower for LTS-ES
(6 of 118 eyes, 5.1%) compared to Wies (14 of 43 eyes, 32.6%;
p<0.0001), Wies-R (7 of 28 eyes, 25%; p=0.0035), and both nonLTS-ES procedures combined (21 of 71 eyes, 29.6%; p=<0.0001).
The proportion of cases requiring re-operations was not significantly
lower for LTS-ES (3 of 118 eyes, 2.5%) compared to Wies-R (3 of
28 eyes, 10.7%; p=0.0848), but significantly lower compared to Wies
(9 of 43 eyes, 20.9%; p=0.0004), and both non-LTS-ES procedures
combined (12 of 71 eyes, 16.9%; p=0.0006).
Conclusions: The LTS-ES procedure was associated with higher
rates of success with no suboptimal outcome (94.9%), compared to
the Wies (67.4%) or Wies-R (75%) procedures. LTS-ES addresses
lateral canthal tendon laxity and retractor attenuation, resulting in
effective repair of involutional entropion. To our knowledge, our
study is the first to directly compare surgical outcomes for LTS+ES,
Wies and Wies-R procedures.
Commercial Relationships: Ru-ik Chee, None; Gary J. Lelli,
None; Benjamin M. Levine, None; Lorraine Cassidy, None
Program Number: 4746 Poster Board Number: D0191
Presentation Time: 11:00 AM–12:45 PM
Eyebrow position following upper blepharoplasty
Adam Weber1, Suhail Dar2, Tal Rubinstein1, Julian D. Perry1. 1Cole
Eye Institute, Cleveland Clinic, Cleveland, OH; 2Case Western
Reserve School of Medicine, Cleveland, OH.
Purpose: To evaluate the effect of upper blepharoplasty on eyebrow
height, accounting for ocular dominance, fat excision, change in
MRD1, and degree of dermatochalasis.
Methods: Retrospective review of patients undergoing upper
blepharoplasty between January 2013 and July 2014. Patients
with a prior history of ocular trauma, disease, and surgery were
excluded. Digital photographs were analyzed using NIH ImageJ
software to measure pre and postoperative eyebrow height at the
medial, central, and lateral positions, MRD1, and dermatochalasis.
Univariable comparisons of brow height and MRD1 were performed.
A multivariate analysis was used to assess for the effect of percentage
change in MRD1 and dermatochalasis and of ocular dominance and
fat excision in mean percentage change of eyebrow height.
Results: Charts of 19 patients were reviewed. Mean age was 73.2
years (SD = 8.86). There were 9 male (47.4%) and 10 female
(52.6%) patients. There were 11 right eye dominant (57.9%) and 8
left eye dominant (42.1%) patients. 13 patients (68.4%) underwent
fat removal. A univariable comparison found insufficient evidence to
suggest a significant change from 0 postoperatively in brow height at
all positions. A multivariable comparison found insufficient evidence
to suggest MRD1, ocular dominance, or dermatochalasis were
significantly associated with mean percentage change in brow height
at all positions with or without fat excision.
Conclusions: Upper blepharoplasty does not change eyebrow height
at the medial, central, or lateral positions, after accounting for any
impact of ocular dominance, fat excision, change in MRD1, or degree
of dermatochalasis.
Commercial Relationships: Adam Weber, None; Suhail Dar,
None; Tal Rubinstein, None; Julian D. Perry, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 4747 Poster Board Number: D0192
Presentation Time: 11:00 AM–12:45 PM
Surgical Outcomes and Dry Eye Symptoms following Anterior
or Posterior Approach Blepharoptosis Surgery in the Elderly
Patient
Saba Alniemi1, Ahsen Hussain2, David Hodge1, Elizabeth Bradley1.
1
Department of Ophthalmology, Mayo Clinic, Rochester, MN; 2St.
Paul’s Eye Unit, Liverpool, United Kingdom.
Purpose: Dry eye symptoms increase in the elderly and following
blepharoptosis surgery. This study aims to compare the surgical
outcomes and prevalence of dry eye symptoms following
blepharoptosis surgery in patients ≥ 80-years-old when compared to
younger, case matched controls.
Methods: A retrospective chart review of 166 patients ≥ 80-years-old
who were post-blepharoptosis surgery (+/- blepharoplasty), through
an anterior or posterior approach for involutional ptosis at the Mayo
Clinic in Rochester, MN, between January 1, 1990 and December 31,
2010 was performed.
A younger case matched control group of 169 patients ≥40 and
≤79-years-old who had undergone the same operation(s) within 12
months of one another was also reviewed. Patients with history of
corneal graft, conjunctival surgery, ocular surface disease besides
dry eye, history of trauma, previous ptosis surgery within the past 10
years, neurogenic ptosis, mechanical ptosis, or the inability to follow
up within 6 months of surgery were excluded.
Results: A total of 335 consecutive patients were included in the
study: 169 younger patients (mean age 67.4, SD 7.79) and 166
elderly patients (mean age 83.8, SD 3.37). The majority of patients
were female (57%) and Caucasian (96.4%). There were more
non-white patients in the younger group (p=0.02). The majority of
patients (55.8%) underwent a combined levator advancement and
blepharoplasty. Preoperatively, 134 patients (40%) reported dry-eye
symptoms. At the first post-op visit (mean 14 days), 35 (10.5%)
patients had new or worse dry-eye. This increased to 58 (17.3%)
patients by the second post-op visit (performed within 6 months).
No significant difference was found between the groups for new or
worse dry-eye at the 1st or 2nd post-op visit (p=0.54). The presence
of preoperative dry-eye had no relation to worsened symptoms by
6 months (p=0.17). Pre-operative mean reflex distance 1 (MRD1)
was smaller (p=0.002) for the 80+ group. There was no significant
difference in surgeon, gender, procedure type, MRD1 post-op, MRD1
asymmetry post-op, or complication rate between the two groups
(p-values >0.05).
Conclusions: Dry eye symptoms and adverse surgical outcomes
were not found to be increased post-blepharoptosis surgery (+/blepharoplasty) in the elderly population when compared to younger
case-matched controls.
Commercial Relationships: Saba Alniemi, None; Ahsen Hussain,
None; David Hodge, None; Elizabeth Bradley, None
Support: Research to Prevent Blindness
Program Number: 4748 Poster Board Number: D0193
Presentation Time: 11:00 AM–12:45 PM
Congenital Blepharoptosis: Clinical Characteristics and Surgical
Outcomes in Mexican Population
Cesar M. Portilla-Espinosa, Pablo J. Guzman-Salas, Jose L. TovillaCanales. Instituto de Oftalmologia Fundacion Conde de Valenciana,
Cuahutemoc, Mexico.
Purpose: Report the number and clinical characteristics of patients
with congenital ptosis who underwent surgery and their outcome in a
period of time.
Methods: Retrospective case series study in one academic tertiary
care Oculoplastics and Orbit Department with 243 patients diagnosed
with congenital blepharoptosis from January 2007 to January 2014.
We reviewed clinical electronic records from patients of “Instituto
de Oftalmologia Conde de Valenciana” in Mexico City, regarding
the following: age, gender, eye (s) affected, palpebral fissure,
ptosis severity graded as no ptosis (100 mm or more), mild (80-99
mm), moderate (40-79 mm) and severe (0-39 mm) on their first
consultation, type of surgery (if practiced); palpebral fissure and
ptosis severity after surgery.
Results: The total population for this study was 243 patients.
Average age of 7.95±10.13 years, with 139 (57.2%) males and 99
(40.7%) females. 90 patients (37%) had only their right eye affected,
124 patients (51%) had only their left eye affected and 29 patients
(11.9%) had both eyes affected. Average palpebral fissure 60.2±16.2
mm. We had 159 (65.4%) patients with moderate ptosis, 44 (18.1%)
with mild ptosis, 39 (16%) with severe ptosis, and 1 patient without
ptosis (0.4%). 134 (55.1%) underwent surgery, of which 55 (41%
of this specific surgery group) had frontal suspension, 38 (28.3%)
had resection and reinsertion of aponeurosis, 14 (10.4%) had
supramaximal reinsertion, 1 (0.7%) had Fassanella-Servat and 1
(0.7%) had Mullerectomy. After surgery the average palpebral fissure
was 79.4±15.2 mm. After surgery, 51 patients (46.8%) had mild
ptosis, 43 (39.4%) had moderate ptosis, 14 (12.8%) had no ptosis and
1 (0.4%) remained with severe ptosis.
Conclusions: We had a predominant male population in the first
decade of life, with the majority having only one eye affected; most
had mild to moderate ptosis and half of them were treated with
surgery. The most practiced surgery was frontal suspension and the
outcomes were mostly satisfactory. This study provides valuable
epidemiological information for and is the first of its kind in Mexico.
Commercial Relationships: Cesar M. Portilla-Espinosa, None;
Pablo J. Guzman-Salas, None; Jose L. Tovilla-Canales, None
Program Number: 4749 Poster Board Number: D0194
Presentation Time: 11:00 AM–12:45 PM
Buccal mucous membrane grafting for cicatricial entropion
Hee-Bae Ahn, Seoung Hyun An, Choi Woo seok, Eun Jung Sohn.
Ophthalmology, Dong-A University Hospital, Busan, Korea (the
Republic of).
Purpose: To evaluate the use of anterior lamellar recession or
posterior lamellar resection with buccal mucous membrane grafting
for treatment of cicatricial entropion.
Methods: A retrospective chart review was performed of all cases of
anterior lamellar recession or posterior lamellar resection with buccal
mucous membrane grafting performed by one surgeon for cicatricial
entropion or trichiasis of the upper or lower eyelids from June 2008
to May 2014. The height of each graft was measured during and after
surgery and the amount of contraction was measured for each graft.
Results: 12 eyelids underwent anterior lamellar recession, 14
eyelids underwent posterior lamellar resection and all patients had
procedure of buccal mucosal graft. 26 eyelids (14 upper lids, 12
lower lids) were identified in 16 patients. The patients’ mean age
was 56.3 years. The mean follow-up period was 7.9 months (range
2-24 months). One eyelid underwent repeat grafting for recurrent
entropion secondary to graft dislocation. The mean graft contraction
rate was 18% after 12 months. There was a reduction in the frequency
of patients reporting discomfort, foreign body sensation, tearing
and pain following treatment in 23 eyelids. 2 eyelids had recurrent
entropion that was managed by electrolysis or cilia epilation.
Conclusions: Minimal graft contraction can be anticipated with the
use of mucosal graft. Anterior lamellar recession or posterior lamellar
resection with buccal mucous membrane grafting in patients with
cicatricial entropion is a simple and cosmetically effective procedure
without complications.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Commercial Relationships: Hee-Bae Ahn, None; Seoung Hyun
An, None; Choi Woo seok, None; Eun Jung Sohn, None
Program Number: 4750 Poster Board Number: D0195
Presentation Time: 11:00 AM–12:45 PM
Prevalence of the Histopathologic Etiologies of Lacrimal Gland
Lesions
Judy Chen, Vinay K. Aakalu, Pete Setabutr. Ophthalmology,
University of Illinois Chicago, Chicago, IL.
Purpose: To describe the prevalence of the etiologies of lacrimal
gland lesions treated at a tertiary, urban referral center in the United
States, as proven by histopathologic diagnosis from surgical biopsy.
Methods: A retrospective chart review was performed of the clinical
records of patients who underwent lacrimal gland biopsy by the
oculoplastics service from 2010 to 2014 at a tertiary, urban referral
center in the United States. Data such as patient demographics,
clinical presentation, imaging studies, and pathologic diagnosis were
recorded.
Results: Forty patients with lacrimal gland lesions were identified.
Twenty-eight (70%) of patients were female and twelve (30%) were
male. The average age at presentation was 42±14 years. Eleven
(28%) of patients presented with bilateral disease while twenty-nine
(72%) presented with unilateral disease. Symptomatically, nineteen
(48%) presented with pain, ten (25%) with visual acuity changes, ten
(25%) with diplopia, thirty-two (80%) with lid swelling, twenty-four
(60%) with injection, six (15%) with globe displacement, seventeen
(43%) with ptosis, and ten (25%) with restriction of extraocular
motility. The average duration of symptoms was 51 weeks (range 1
day to 8 years). The most common histopathologic diagnosis was
dacryoadenitis (52.5%, n=21), followed by orbital inflammatory
syndrome (15%, n=6) and sarcoidosis (10%, n=4). One case each
was noted of hemangiopericytoma infiltrating the lacrimal gland,
pleomorphic adenoma, recurrent follicular lymphoma, Sjogren’s
disease, prolapsed orbital fat, IgG4 sclerosing disease, eosinophilic
angiocentric fibrosis (EAF), glass retained foreign body, and retained
lacrimal stones.
Conclusions: Lacrimal gland lesions constitute a small portion of
patients referred to tertiary care centers. While the vast majority
of histopathologic etiologies are inflammatory – specifically
dacryoadenitis, orbital inflammatory syndrome, and sarcoidosis –
no clinical or imaging features reliably differentiate inflammatory
from neoplastic causes. Therefore, lacrimal gland biopsy with
histopathologic diagnosis should remain the standard of care.
Commercial Relationships: Judy Chen, None; Vinay K. Aakalu,
None; Pete Setabutr, None
Support: NH Grant EY001792, Unrestricted Grant from RPB
Program Number: 4751 Poster Board Number: D0196
Presentation Time: 11:00 AM–12:45 PM
Botulinum toxin injection in the palpebral lacrimal gland for the
management of epiphora
Imtiaz A. Chaudhry1, Farrukh A. Shamsi2, Yonca O. Arat3, Waleed
A. Al-Rashed4, Osama Al-Sheikh4, Milton Boniuk5. 1Houston
Oculoplastics Associates, Memorial Herman Med Plaza TX Med Ctr,
Houston, TX; 2Research Department, King Khaled Eye Specialist
Hospital, Riyadh, Saudi Arabia; 3University of Wisconsin, Madison,
WI; 4King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia;
5
Baylor College of Medicine, Houston, TX.
Purpose: To report our experience with Botulinum toxin injections
into the palpebral lacrimal gland through transconjunctival approach
in the management of epiphora due to different causes.
Methods: We reviewed our experience with transconjunctival
Botulinum toxin injection (2.5 - 5 U) in the palpebral lacrimal galnd
of 56 adult patients in the management of epiphora due to different
causes. Some of the causes of epiphora in our patients included
crockadile tears (gustatory) secondary to aberrant regeneration of
the facial nerve after facial nerve palsy, epiphora despite patent
functional nasolacrimal system, ideopathic hypersecretion, persistent
partial epiphora despite successful lacrimal drainage sugery and
reflex tearing due to different causes.
Results: Fourty-eight (86%) of our patients reported improvement
from the Botulinum injections into their palpebral lacrimal gland
through transconjunctival approach in the form of significantly
decreased symptoms of epiphora. Patients remained symtpoms
free between 2 to 6 months (average 4.4 month) after Botumlinum
injection. Complications were low and inlcuded subconjunctival
hemorrhage at the site of injection in 6 patients and transient diplopia
in 2 patients and ptosis in 2 patients. Both the transient diplopia and
ptosis resolved in 1 to 3 weeks in all patients.
Conclusions: Use of a single Botulinum toxin injection into the
palpebral lobe of the lacrimal galnd through transconjunctival
approach may be a viable option in adult patients with epiphora due
to differnet causes with relatively mninimal complications.
Commercial Relationships: Imtiaz A. Chaudhry, None; Farrukh
A. Shamsi, None; Yonca O. Arat, None; Waleed A. Al-Rashed,
Xeoman (S); Osama Al-Sheikh, None; Milton Boniuk, None
Program Number: 4752 Poster Board Number: D0197
Presentation Time: 11:00 AM–12:45 PM
A 4-year retrospective chart review of sphenoid wing
meningiomas
Anjulie K. Quick1, Alina V. Dumitrescu1, Jason Sokol1,
Thomas Whittaker1, Roukoz B. Chamoun2, Paul J. Camarata2.
1
Ophthalmology, University of Kansas Medical Center, Kansas City,
KS; 2Neurosurgery, University of Kansas Medical Center, Kansas
City, KS.
Purpose: Sphenoid wing meningiomas (SWM) are benign invasive
tumors that can cause significant ocular morbitity. The aim of this
study was to determine the demographics, clinical exam and imaging
findings, and post operative outcomes in our population of patients.
Methods: A retrospective, descriptive, chart review was performed
after IRB approval. All biopsied/surgically removed orbital lesions
treated in our department between 2010 and 2014 were identified by
surgical CPT codes. Those patients with SWM were then identified.
In each case gender and age of the patients, pathological diagnosis,
and laterality were registered.
Results: Out of 141 patients identified during chart review, 8
patients met criteria for SWM over a 4-year period. There was a
predominance of female patients (87%) and average age at the time
of diagnosis was 55. Patients presented with proptosis (4), visual
loss (2), jaw pain (1), and subdural hematoma (1). 75% of patients
presented with visual acuity 20/25 or better. Major clinical findings
included afferent pupillary defect (6), average of 3.5 mm increase
in proptosis, ophthalmoplegia (4), and diplopia (4). 87% of patients
had formal visual fields and of those, 85% had an inferior field
defect. Post resection, two of the patients who had repeat visual fields
showed similar defects as before surgery. Computed tomography
(CT) and magnetic resonance imaging (MRI) were the imaging of
choice in all patients. 62% were correctly identified as SWM by
radiologist on MRI. Imaging findings consistent with SWM included
hyperostosis, homogenous enhancing mass, and osseous involvement.
All tumors were removed by an oculoplastics surgeon with an
orbitozygomatic approach with collaboration from neurosurgery.
Diagnosis was confirmed by pathology report. Post-operatively,
62% of patients experienced ptosis and in all patients visual acuity
improved or remained the same.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Conclusions: SWM present a unique situation that combines the
efforts of ophthalmology and neurosurgery. An ophthalmologist may
be the first person to recognize the tumor as the majority of patients
present with ocular complaints. Although those with compressive
optic neuropathy from SWM maintain good vision they can still have
residual pupillary defects and visual field loss. An orbitozygomatic
surgical approach is a safe and effective method for removal of
SWM. Future research involves exploring genetic and pathologic
markers.
Commercial Relationships: Anjulie K. Quick, None; Alina V.
Dumitrescu, None; Jason Sokol, None; Thomas Whittaker, None;
Roukoz B. Chamoun, None; Paul J. Camarata, None
Program Number: 4753 Poster Board Number: D0198
Presentation Time: 11:00 AM–12:45 PM
Modified multipare Z-plasty surgery to correct the angular
deformity of the eyelid after injury
Huayi Lu2, 1, Yaru Dong1. 1Ophthalmology, JiLin university,
ChangChun, China; 2Ophthalmology, University of Louisville,
Louisville, KY.
Purpose: The longitudinal scar in the eyelids tissue can make
the eyelid to angular deformity, even to be the greater risk of
lagophthalmos ectropion or exposure keratitis.Those disease may
impact nomal vision. Eyelid angular deformity correction surgery can
restore the eyelid function and change patients’s appearance
Methods: 7 eyelids of 7 patients (1 woman, 6 men) underwent this
procedure. Gentian violet was used to draw a line on the eyelid scar
place. Sliced incision was placed through the skin and subcutaneous
tissue, The scar tissue was resected, The meibomian was cut along
dislocation healing lineand completely release eyelid so that the
eyelid could returned to normal range of activity .The meibomian was
sutured and make it to a normal radian. 4-5 groups of Z lines were
drawed along the direction of skin incision by gentian violate . Then
the skin incision were placed and according the line of the tension,
exchange the position of the flap. Subcuteous tissue were suture
by 6/0 absorbable suture and the skin were sutured by 6/0 nylon
suture line nodular skin suture. Functional and cosmetic results were
evaluated and the advantages of this technique were stressed.
Results: Mean age was 34.0 years (range 26 - 50) with a mean
follow-up period of 12 months (range 6 - 22). All cases eyelids
achieved good to excellent final lid positions and adequate cosmetic
results with no postoperative complications. On the basis of our
experience and the bibliography reviewed, we decided to use the
multipare Z-plasty surgery can effectively prevent the recurrence of
eyelid angular deformity after postoperative scar contraction. We
found it was a good election for this patient since we achieved good
functional, anatomical, and aesthetical results.
Conclusions: Multipair transposition flap is a effectively treatment
for eyelid angular deformity. Because of the multipair transposition
flap changed the scar traction direction, and effectively decrease
the intensity of the wounded skin in the length of the main shaft
direction, so can effectively prevent postoperative scar contraction
appear again eyelid angular deformity.
Commercial Relationships: Huayi Lu, None; Yaru Dong, None
Program Number: 4754 Poster Board Number: D0199
Presentation Time: 11:00 AM–12:45 PM
Dermoid Cysts: Imaging in the prevention of complications
Lucas T. Lenci, Meredith Baker, Richard C. Allen. Ophthalmology
and visual sciences, university of iowa, Iowa City, IA.
Purpose: Dermoid Cysts are common lesions in the periocular
region. They account for approximately 5% of all orbital lesions (1).
The majority arise in children in the superotemporal region from
the frontozygomatic suture (2). To our knowledge, there has been
no study evaluating decisions about when/if to image patients with
presumed dermoid cysts. The purpose of this study is to determine
clinical characteristics which may guide imaging decisions in the
management of presumed dermoid cysts.
Methods: A retrospective chart review was performed on our
dermoid cyst patient database at the university of Iowa over the last
5 years. Clinical, pathologic and imaging data were obtained. We
analyzed whether the imaging data obtained changed the patients
course. We defined a change in management if an alternate diagnosis,
significant intraorbital or intracranial extension, or significant bony
erosion was found.
Results: 57 patients charts met our criteria. The mean age was 6.4
years with 21 females and 36 males. 40/57 (70%) were located
superotemporally and 10 (18%) superomedially. 27/57 (47%)
patients obtained imaging mostly in the form of CT or MRI. 42/57
(74%) patients had comments about mobility. 12 (21%) lesions
were immobile. 8 (14%) cases of gross rupture during surgery were
found. 3 were located medially (21% chance of rupture), 5 laterally
(12%). Imaging changed management in 3/27 (11%) cases that had
imaging and only 3/57 (5%) total cases. Each of these cases had
other significant clinical findings including new onset strabismus,
proptosis, and recurrence. The average age was 28.8 for these
complicated lesions, which also had no mobility on exam.
Conclusions: There is little to no guidance on when dermoids
should be imaged. Management was altered by imaging in only
3/57 (5%) total patients, while 47% of patients underwent imaging.
Location of the dermoid doesn’t seem to have an impact on
management, however medial lesions tend to have an increased risk
of intraoperative rupture (21%). Orbital findings such as proptosis,
strabismus, or significant mass effect are reasons to obtain imaging
as well as recurrence and older age. Lack of mobility was seen in all
of our complicated dermoids. Medial canthal lesions have not been
associated with intracranial extension or misdiagnosis in our case
series, which is similar to other studies (3,4). Thus, imaging is likely
not necessary for periocular dermoid lesions without other clinical
findings.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Commercial Relationships: Lucas T. Lenci, None; Meredith
Baker, None; Richard C. Allen, None
Program Number: 4755 Poster Board Number: D0200
Presentation Time: 11:00 AM–12:45 PM
Evisceration of Eyes with Intraocular Erosion of MIRAgel
Scleral Buckles
Tal Rubinstein, Julian D. Perry, Rao Chundury. Ophthalmology,
Cleveland Clinic, Cleveland, OH.
Purpose: MIRAgel (hydrogel) scleral buckles have been associated
with significant complications such as orbital inflammation,
intraocular erosion, and endophthalmitis. Patients with intraocular
erosion in a painful, blind eye may benefit from evisceration to
remove the intraocular contents and the inciting MIRAgel material.
We explore preoperative and intraoperative findings of such
eviscerations and their postoperative course. Further, we define
a method of transocular-approach orbitotomy to remove orbital
components of the scleral buckle through the eviscerated eye.
Methods: This is an IRB approved, retrospective case series of
consecutive patients who underwent evisceration at the Cleveland
Clinic between the years 2000 and 2014. Patients were included if
they had concurrent explantation of MIRAgel scleral buckle material;
all other patients were excluded. Patient files were searched for
age, gender, laterality, pre-operative findings, pre-operative ocular
imaging, intraoperative surgical procedure and findings, postoperative findings, complications, and duration of follow up.
Results: Preliminary review identified four patients who met criteria.
All were female with an average age of 65.25 years (range 55-80).
All patients had blind, painful eyes; one also had endophthalmitis.
Two of four pre-operative B-scans identified intraocular erosion
of the scleral buckle. One evisceration was performed in 2002,
the rest between 2011-2013. Three of four eviscerations were left
eyes. All eviscerations identified intraocular MIRAgel components.
All eviscerations were concurrently performed with orbitotomies
for removal of orbital MIRAgel components, of which three were
performed through a trans-ocular approach into the orbit. Average
follow up time was 17.5 months (range 1-36). Two patients needed
subsequent external levator resection to help with prosthetic
retainment. One patient had inability to maintain prosthesis due to
adhesions and foreshortened inferior fornix.
Conclusions: MIRAgel scleral buckles should be avoided as they
may lead to devastating complications such as intraocular erosion
of the material. Evisceration of blind, painful eyes with concurrent
explantation of orbital MIRAgel material can be done through a
transocular-approach orbitotomy, which increases efficiency and
reduces additional approaches of entering the orbit. Prior scarring and
extensive dissection of the MIRAgel may compromise post-surgical
results.
Commercial Relationships: Tal Rubinstein, None; Julian D.
Perry, None; Rao Chundury, None
Program Number: 4756 Poster Board Number: D0201
Presentation Time: 11:00 AM–12:45 PM
Plasma surface modification of porous polyethylene implants in
orbital reconstruction
Seong-Won Yang1, Saemi Park2. 1Ophthalmology, Chosun University
Hospital, Gwangju, Korea (the Republic of); 2Ophthalmology, Kim’s
eye hospital, Seoul, Korea (the Republic of).
Purpose: Various alloplastic materials are used in orbital wall
reconstruction. We investigated the pre-osteoblast adhesion and
osseointegration on porous polyethylene (PE) with hydrophobic
surface using a plasma surface treatment.
Methods: Surface modified PE was prepared by oxygen or nitrogen
plasma. After plasma treatment, adhesion and differentiation of
MC3T3-E1 cells was evaluated using a MTT assay and alkaline
phosphatase (ALP) activity respectively. A total of 10 white rabbits
orbital medial, inferior, and maxilla bone were exposed. After that,
pre-treated implant was inserted. Micro-CT, Immunostaining were
performed before exposure, 4 weeks, and 8 weeks, afterward to allow
for serial comparisons.
Results: Plasma-treated PE implants significantly increased
cell adhesion and ALP activity and up-regulated expression of
osteogenesis-related genes such as alkaline phosphatase, osteopontin
and osteocalcin in MC3T3-E1 cells. In vivo results showed that
plasma-treated samples demonstrate the good bone formation than
the control.
Conclusions: Plasma-treated porous polyethylene can be used as a
useful material for Orbital fracture.
Commercial Relationships: Seong-Won Yang, None; Saemi Park,
None
Program Number: 4757 Poster Board Number: D0202
Presentation Time: 11:00 AM–12:45 PM
Viability, Structural Integrity and Aqueous Humor Dynamics are
Established in an Orthotopic Whole Eye Transplant Model
Kia M. Washington1, Yang Li1, 2, Bo Wang3, 4, Maxine R. Miller1, 3,
Yolandi van der Merwe3, 4, Leon Ho3, 4, Michael Steketee3, Joel S.
Schuman3, 4, Kevin C. Chan3, 4, Vijay S. Gorantla1. 1Department of
Plastic and Reconstructive Surgery, UPMC, VCA Lab, Pittsburgh,
PA; 2Department of Plastic and Reconstructive Surgery, Xijing
Hospital, Fourth Military Medical University, Xi’an, China;
3
Department of Ophthalmology, UPMC Eye Center, Ear and Eye
Institute, Ophthalmology and Visual Science Research Center,
Pittsburgh, PA; 4Department of Bioengineering, Swanson School of
Engineering, University of Pittsburgh, Pittsburgh, PA.
Purpose: Approximately 39 million people worldwide suffer
from blindness. The permanent nature of vision loss is largely due
to the inability of retinal ganglion cells to regenerate. Whole eye
transplantation (WET) gives the opportunity to provide viable
retinal ganglion cells and an entire optical system to recipients with
irreversible vision loss. The purpose of our study is to evaluate
viability, structural integrity and aqueous humor dynamics in our
orthotopic whole eye transplant model.
Methods: Syngeneic transplants were performed in Lewis (RT1l)
rats. Donor flaps are composed of ocular tissue anterior to the optic
chiasm, the skin of the eyelid and external ear. Recipient sites are
prepared by removing a similar region of skin and ocular tissue with
the optic nerve cut at the base of the globe. Grafts are transplanted
to the recipient, vascular anastomoses are performed, as are nerve
appositions between donor and recipient optic nerves. Slit lamp
examination, Optical Coherence Tomography (OCT) and histological
analysis were performed to evaluate the viability and structural
integrity of the transplanted eye. Gadolinium (Gd)-enhanced MRI
was employed to evaluate ocular physiology of the transplanted eye.
Results: 15 of 22 rats survived the surgical procedure with the
maintenance of visual transparency of the anterior eye as evidenced
by slit lamp examination. Some peripheral corneal neovascularization
was seen in all eyes. OCT confirmed transparency of the cornea
and lens, preservation of the retina, and blood flow to the eye. Gdenhanced MRI revealed the presence of transplanted eye aqueous
humor dynamics and intact blood-ocular and aqueous-vitreous
barriers. Histology confirmed corneal neovascularization and
preserved retinal integrity, with the exception of retinal nerve fiber
layer and ganglion cell layer thinning.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Conclusions: We have established a viable orthotopic model for
vascularized whole eye transplantation in the rat. Maintenance of
structural integrity, viability and aqueous humor dynamics were
confirmed. The model is excellent for studying viability, functional
return and immunology in WET.
Figure 1: A., B. & C. Donor hemi-face flap D. Long term survival of
the WET transplanted recipient
Program Number: 4758 Poster Board Number: D0203
Presentation Time: 11:00 AM–12:45 PM
Revision of failed external dacyrocystorhinostomy with
endoscopic-guided balloon dilation.
Christopher Lo, Payal Patel, Carisa Petris, Richard Lisman.
department of ophthalmology, nyu, New York City, NY.
Purpose: Various approaches to revising primary
dacyrocystorhinostomy (DCR) have been presented without
consensus on technique. We performed a retrospective, observational
study of a single surgeon’s experience that introduces a novel
minimally invasive approach to revise failed external DCR that is
safe, repeatable and avoids an external scar. The technique requires
limited endoscopic manipulation and the surgeon may become
proficient without advanced training.
Methods: An institutional chart review of a single surgeon’s
experience with six patients with recurrent epiphora. All patients
were status-post external DCR, and had documented recurrence of
epiphora and reflux upon irrigation. Study patients subsequently
underwent endoscopic-guided balloon DCR using 3 and 5 mm
balloon catheters. Surgical success was defined by a patent surgical
ostium demonstrated by absence of subjective epiphora and irrigation
of saline through nasolacrimal system at 1 week, 1 month and 3
month visits.
Results: All (100%) patients had subjective epiphora and
documented reflux of saline upon irrigation of the nasolacrimal
system following an external DCR. Average length of time between
primary and revision DCR was 55.2 months. Intraoperative steroid
injection around the osteotomy scar was used in 50% of study
patients. All six patients completed at least 3-months followup. Surgical success was achieved in all secondary endoscopic
revisions. All (100%) patients had improvement of epiphora at 1
week, 1 month, and 3 month visits. Five (83.3%) patients described
complete resolution of epiphora; one (16.7%) patient described 50%
improvement of symptoms. All study patients had patent irrigation of
saline through nasolacrimal system at post-operative visits.
Conclusions: Secondary external DCR to revise failed DCR can
be surgically challenging, require invasive manipulation, and lead
to increased scarring. Although primary endoscopic DCR requires
advanced endoscopic expertise, secondary endoscopic-guided balloon
DCR can be safely performed without advanced technique, provides
direct visualization to ensure surgical accuracy, and avoids additional
external incisions. Based on our results, this technique promises to
have an excellent success rate and may be readily incorporated into
surgical practice.
Figure 2. OCT. Control (top row) Transplant (bottom row)
Figure 3. T1-weighted images at 0-10min (left) and 60-70 min (right)
after Gd administration 3 weeks after WET
Commercial Relationships: Kia M. Washington, None; Yang
Li, None; Bo Wang, None; Maxine R. Miller, None; Yolandi van
der Merwe, None; Leon Ho, None; Michael Steketee, None; Joel
S. Schuman, Zeiss (I); Kevin C. Chan, None; Vijay S. Gorantla,
None
Support: National Institutes of Health CORE Grant P30-EY008098;
The Louis J. Fox Center for Vision Restoration of UPMC and the
University of Pittsburgh; Eye and Ear Foundation of Pittsburgh, PA;
An unrestricted grant from Research to Prevent Blindness, New
York, NY; The VA Pittsburgh Healthcare System; Office of the
Assistant Secretary of Defense for Health Affairs under Award No.
W81XWH-14-1-0421
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
± 3 months in this group. It was noted 3 postoperative complications
(10%) with this technique.
Conclusions: Antegrade balloon dacryocystoplasty is an effective,
non-invasive technique for treatment of partial PANDO in adults.
This technique seems to be better than silicone intubation in this
indication. Nevertheless, further prospective and comparative studies
are needed to consolidate this promising results.
Commercial Relationships: Yoann Soldermann, None; Olivier
Galatoire, None; jacomet pierre vincent, None
Endoscopic view of dilated balloon catheter (arrow) through fibrotic
osteotomy (asterisk).
Commercial Relationships: Christopher Lo, None; Payal Patel,
None; Carisa Petris, None; Richard Lisman, None
Program Number: 4759 Poster Board Number: D0204
Presentation Time: 11:00 AM–12:45 PM
Efficacy and tolerance of balloon dacryocystoplasty in partial
primary acquired nasolacrimal duct obstruction
Yoann Soldermann1, Olivier Galatoire2, jacomet pierre vincent2.
1
Ophtalmology, Centre Hospitalier Lyon Sud, Lyon, France;
2
Rothschild ophtalmological fondation, Paris, France.
Purpose: The main cause of tearing in adult is Primary Acquired
Nasolacrimal Duct Obstruction. Stenosis is first partial, related to
an inflammatory mucosal remodeling. The objective of this study
is to evaluate the efficacy and the safety of antegrade balloon
dacryocystoplasty in adults with a partial PANDO.
Methods: This is a prospective and a single center study. 35
nasolacrimal ducts of 24 patients, unresponsive to medical
treatment, were included between February 2011 to August 2014.
The patients with other causes of tearing, including dry eye and
eyelid malposition, were excluded. All included patients passed a
dacryoscanner before treatment. The anterograde dilatation using
a balloon catheter (Ophtacath®, FCI, Paris) was performed in
operating room under general anesthesia. A 9 atmospheres expansion
during 90 sec on the first mark and during 60 seconds on the second
mark treated all the nasolacrimal duct. The endpoint was the Munk’s
tearing score at 1, 3, 6, 12 and 24 months. A complete success was
defined as a Munk’s score of 0 or 1.On the other hand, a retrospective
analysis was performed on 29 nasolacrimal ducts of 19 patients
treated with a silicone intubation for tearing due to a partial stenosis
between 2007 and 2013.
Results: The average age of our patients was 65 ± 2 years. The
mean duration of tearing before treatment was 3 ± 0.5 years. 77%
of patients were women. The procedure were achieved in 100%
of cases. 30 tearing improved with this procedure : 86% of cases
(30/35). Complete success was effective for 20 nasolacrimal ducts :
57% of cases (20/35). The mean follow-up was 17 ± 3 months. No
recurrence of tearing was observed during the monitoring period.
4 postoperative complications were recorded (11.8%): 1 orbital
emphysema, 2 periorbital hematomas and 1 epistaxis. With silicone
intubation, tearing improved in 37.9% of cases and a complete
resolution was found in 27.6% of cases. The mean follow-up was 29
Program Number: 4760 Poster Board Number: D0205
Presentation Time: 11:00 AM–12:45 PM
Use of a self-retaining bicanalicular nasolacrimal stent for partial
nasolacrimal obstruction in adults without need for general
anesthesia
David Silbert. Family Eye Group Vision Science Department,
Lancaster, PA.
Purpose: Partial nasolacrimal duct (NLD) obstruction has been a
challenging problem to treat short of placing crawford tubes under
general anesthesia. We perform a retrospective observational study
utilizing a bicanalicular self-retaining stent in adults without general
anesthesia.
Methods: Kaneka Lacriflow stents were placed in the office
under topical/local anesthetic or in conjunction with other eyelid
surgery under conscious sedation. Ages of patients ranged from
33 to 90 years. Patients with epiphora due to punctal, canalicular
or nasolacrimal stenosis were included. Irrigation was used to
confirm the absense of complete obstruction. Local blocks to the
infratrochlear nerve, eyelid and lidocaine gel infiltrated through the
NLD were utilized. Stents were placed with a stylet to both upper and
lower punctum. Stents were left in place for 3 months then removed.
Improvement in epiphora was assessed one month later. An antibiotic
steroid drop was used for 2 weeks after implantation and for 2 weeks
following removal.
Results: 27 patient were included. 14 patients had bilateral surgery
and 13 had unilateral. A total of 41 NLD were included in the study.
In one patient the stent could not be passed down the NLD. Stent
placement was succesful in 40/41 NLD (98%) with no patient
complaining of excessive discomfort. In 27 eyes stents were placed
under local anesthesia while 13 were performed under conscious
sedation. 24 patients completed the full 4 months of follow-up while
the rest are still in followup. 22/24 patients reported improvement in
epiphora one month following removal of the stents (92%). 2 patients
reported continued epiphora with stents in place, but improvement
following removal. 1 patient had partial dislodgment of the stent,
which was removed, replaced and then left in place for the full 3
months.
Conclusions: Epiphora due to partial nasolacrimal duct
and canalicular obstruction has been challenging to treat. A
hydrophilic polymer which makes it slippery in the NLD, a smaller
intracanalicular diameter and a larger intraductal diameter allows the
stent to pass easily and self retain. The Kaneka Lacriflow stent was
able to be placed consistently without the need to enter the nose to
recover or tie the stent. 92% of patients had significant improvement
in epiphora without the need for a procedure under general
anesthesia.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
development of tools to quantify the severity of MGD would allow
for more objective outcome measurements.
Remove stylet after placement
Commercial Relationships: David Silbert, Kaneka (C), Kaneka (F)
Support: Company support for study (Kaneka)
Program Number: 4761 Poster Board Number: D0206
Presentation Time: 11:00 AM–12:45 PM
Dynamic Intraductal Meibomian Probing (DIMP): A Novel
Approach to the Treatment of Meibomian Gland Dysfunction
Zeba A. Syed, Francis Sutula. Ophthalmology, Massachusetts Eye
and Ear Infirmary, Boston, MA.
Purpose: Meibomian gland dysfunction (MGD) is among the most
common disorders treated by ophthalmologists. Warm compresses
and lid hygiene usually do not provide lasting symptom relief.
Meibomian gland probing has been shown to be effective in severe
posterior blepharitis. Here we describe a modified technique,
Dynamic Intraductal Meibomian Probing (DIMP), which has several
advantages over traditional probing including greater magnification,
stabilization of the patient’s head, facilitated probing against
resistance, and easier identification of orifices
Methods: A retrospective chart review was performed on patients
undergoing DIMP by one physician between January 2013 and
July 2014. Inclusion criteria were patients with symptomatic MGD
(dryness, tearing, foreign body sensation, and/or irritation) and
clinical signs of MGD (eyelid erythema, thickening, irregularity,
and/or telangiectasias) who did not respond to conservative
therapies including warm compresses, lid hygiene, and topical
anti-inflammatory medications. We reviewed the electronic medical
records for the presence of symptoms after DIMP treatment.
During DIMP, the patient is seated supine on a surgical chair and an
operating microscope is positioned over the target lid. Von Graefe
fixation forceps are used to grasp the lid and apply upward traction,
and a 2 mm probe is inserted to dilate each meibomian gland orifice
sequentially along the lid margin. The 4 mm probe is then substituted
to allow for deeper probing. After DIMP, meibum spontaneously
expresses through glands along the lid margin.
Results: Thirty-six eyes of 22 patients underwent DIMP treatment.
The average age of patients was 59 years. Eleven patients were
male and 11 were female. The majority (82%) of procedures were
performed on a lower lid. Follow-up ranged from 1 to 16 weeks, with
a mean of 3.5 months (± 3.1 months). Most (92% ± 4.6%) patients
reported symptomatic improvement during follow-up. No major
complications were noted. Rarely, small areas of bleeding were
appreciated at ductal orifices. This always stopped spontaneously
without need to apply pressure.
Conclusions: DIMP is an effective and safe technique for
symptomatic MGD that is resistant to traditional therapies. The
Dynamic Intraductal Meibomian Probing (DIMP)
Release of Meibum After DIMP
Commercial Relationships: Zeba A. Syed, None; Francis Sutula,
None
Program Number: 4762 Poster Board Number: D0207
Presentation Time: 11:00 AM–12:45 PM
Optical Coherence Tomography and its utility in diagnosing and
managing meibomian gland disease
Anupam Jayaram1, Liza M. Cohen2, Gary Lissner1, Christopher
Chambers1. 1Ophthalmology, Northwestern University, Chicago, IL;
2
Feinberg School of Medicine, Northwestern University, Chicago, IL.
Purpose: Optical Coherence Tomography has recently been shown to
have utlity in assessing tear meniscus as well as imaging meibomian
glands. The purpose of this study is to utilitze optical coherence
tomagraphy to quantify meibomian gland dysfunction both before
and after various methods of treatment including artificial tears,
warm compresses, lid scrubs, and oral doxycycline. This objective
measurement of meibomian gland dysfunction after various forms of
management can give better insight into efficacy of treatment.
Methods: A group of 10 healthy subjects with no signficant
meibomian glad dysfunction had optical coherence tomography
imaging done of their meibomian glands both at baseline and 6 weeks
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
later, and these images were used as controls. In contrast, a group of
10 subjects with documented severe meibomian gland dysfunction
had ocular coherence tomagraphy taken of their meibomian glands
both at baseline and again 6 weeks after various treatment modalities.
An objective grading system was used to quantify the amount of
meibomian gland dysfunction of each image, and the results were
analyzed to try to find trends in improvment of meibomian gland
dysfunction.
Results: All 10 controls showed no significant meibomian gland
disease both at baseline as well as at the 6 week re-evaluation
mark. All 10 subjects from the experimental group showed 3-4+
meibomian gland dysfunction at baseline imaging and all showed
various amounts of improvement by the 6 week re-evaluation mark.
This study uses images to illustrate the amount of gland plugging in
various meibomian gland dysfunction treatment modalities.
Conclusions: This is the first study to show in an objective and
quantitative fashion that warm compresses and lid scrubs actually
do decrease meibomian gland dysfunction when done correctly.
Additionally, it demonstrates the utility of optical coherence
tomagraphy in diagnosing, following, and managing patients with
severe meibomian gland dysfunction. Finally, the various images of
this study illustrate and provide a better understanding of concepts
like acinar atrophy, gland plugging, and decreased tear meniscus.
Commercial Relationships: Anupam Jayaram, None; Liza M.
Cohen, None; Gary Lissner, None; Christopher Chambers, None
Program Number: 4763 Poster Board Number: D0208
Presentation Time: 11:00 AM–12:45 PM
The Role of Goblet Cells in the development of Dacryostenosis
Ameet Goyal1, Devon Dipalma2, Riya Goyal3. 1Ophthalmology, new
york medical college, Rye, NY; 2Duke, Durhm, NY; 3Hofstra Medical
School, Mineola, NY.
Purpose: The pathogenesis of primary acquired nasolacrimal duct
obstruction(PANDO) has been evaluted in past studies. These
factors include use of make-up, gender, hormone levels, and viral
infection(Kashkouli MB 2010). The anatomy and physiology of
the epithlelial lining of the tear duct has also been well studied
by Paulsen(1998, 2003, and 2008). These studies have elucidated
the tear flow physiology, microbial defense strategies, and
pathophysiological processes in the nasolacrimal duct system. These
studies have also revealed a mucin producing Goblet cell that lines
the mucosal layer of the nasal lacrimal duct. The goblet cells are
involved with the maintenance of the lubrication in order for the tears
to drain through the tear duct. The purpose of this study is to better
understand the role of goblet cells in patients who have PANDO.
Methods: All of the 22 patients were evaluted from one practice in
ophthalmic plastic and reconstructive surgery. These patients were
excluded if they had trauma, infection, previous nasal surgery, or
history of nasal tumor. All of the patients complained of epihora.
Other causes including dry eye, blepharitis, and anatomical
abnormalities of the eye lid were excluded. Patients underwent an
external dacrycystorhinostomy to remove the nasal lacimal duct
mucosa. The tissue was sent in formalin. Hematoxylin and eosin
stained slides cut from paraffin embedded formalin fixed tissues were
examined from 22 lacrimal sac and nasal lacrimal duct mucosa. The
histologic features in each biopsy included degree of inflammation
and inflammatory cell types. All of this tissue was then analyzed by
two independent pathologist at an academic institution.
Results: There were 16 women and 6 men in this study. The
pathologist evlauted the health of the mucosa and the number of
goblet cells present in each specimen. Each one of the specimens
demonstrated chronic infammation. These cell types were either
lymphohistiocytic or lymphopasmacytic. There was also noted to be
a complete absence of goblet cells in the female patients. The male
specimens demonstrated goblet cell in the epithelial mucosa.
Conclusions: This study shows that there appears to be a complete
loss of Goblet cells in the lining of the nasal lacrimal duct in women.
The mucin producing goblet cells are important in the flow of the
tears through the tear duct. The decrease in production of mucin may
be a very important component to the pathophysiology of PANDO.
Commercial Relationships: Ameet Goyal, None; Devon Dipalma,
None; Riya Goyal, None
479 Strabismus, II
Wednesday, May 06, 2015 3:45 PM–5:30 PM
Exhibit Hall Poster Session
Program #/Board # Range: 5204–5230/D0209–D0235
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Contributing Section(s): Clinical/Epidemiologic Research
Program Number: 5204 Poster Board Number: D0209
Presentation Time: 3:45 PM–5:30 PM
Quality of Life Concerns in Parents of Children with Esotropia
Yolanda S. Castañeda1, Eileen E. Birch1, David A. Leske2, Sarah R.
Hatt2, Laura Liebermann2, Jonathan M. Holmes2. 1Retina Foundation
of the Southwest, Dallas, TX; 2Ophthalmology, Mayo Clinic,
Rochester, MN.
Purpose: Esotropia is a common form of childhood strabismus, but
the effects of esotropia on the health related quality of life (HRQOL)
of affected children and their families are poorly understood. As
part of a larger research effort to develop patient-reported outcome
measures for pediatric eye conditions, we interviewed parents of
children with esotropia to identify the specific concerns affecting the
parents HRQOL, distinct from concerns affecting the HRQOL of the
children themselves.
Methods: 35 children with esotropia (aged 2 to 17 years) were
recruited, along with one of their parents. Esotropia types were:
accommodative or partially accommodative (17; 49%), infantile (7;
20%), non-accommodative (6; 17%), consecutive (2; 6%), 6th nerve
palsy (1, 3%), Duane syndrome (1; 3%), and mechanical (1; 3%). 18
(51%) had a current or previous diagnosis of amblyopia and 25 (71%)
wore refractive correction. Individual semi-structured interviews
were conducted with the parent of the child. Transcripts from
recorded interviews were independently evaluated by 2 investigators
using NVivo software. Specific HRQOL concerns were identified
and coded by assigning to themes. Discrepancies were resolved by
discussion. The frequency with which each theme occurred was
calculated.
Results: Overall 18 HRQOL themes were identified, describing
the effects of specific concerns and worries on the parent’s own
HRQOL. The top concern, mentioned by 31 (89%) of 35 parents, was
Inconvenience, especially regarding taking time off work. 30 (86%)
of 35 parents mentioned concerns of Worry regarding treatment e.g.
worrying that treatment won’t work or that other options should be
explored and Negative Emotions such as finding it emotionally hard
or scary to deal with the condition. Having to Compensate or Adjust
for their child’s eye condition e.g. extra supervision, protecting the
child, making sure they sit at the front in class; and problems related
to Treatment were each mentioned by 28 parents (80%).
Conclusions: Parents of children with esotropia express a range
of concerns affecting their own HRQOL, such as having to make
adjustments to help their child, worrying about treatment and
experiencing negative emotions. Identified concerns in esotropia
suggest that pediatric eye disorders may have pervasive effects on
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
multiple aspects of family life, and these concerns will be used to
develop a parent HRQOL instrument.
Commercial Relationships: Yolanda S. Castañeda, None; Eileen
E. Birch, None; David A. Leske, None; Sarah R. Hatt, None;
Laura Liebermann, None; Jonathan M. Holmes, None
Support: NIH Grants EY024333 (JMH), EY018810 (JMH), and
EY022313 (EEB), Research to Prevent Blindness, and the Mayo
Foundation.
Program Number: 5205 Poster Board Number: D0210
Presentation Time: 3:45 PM–5:30 PM
Quality of Life Concerns in Children with Esotropia
Laura Liebermann1, David A. Leske1, Sarah R. Hatt1, Yolanda S.
Castañeda2, Eileen E. Birch2, Jonathan M. Holmes1. 1Ophthalmology,
Mayo Clinic, Rochester, MN; 2Retina Foundation of the Southwest,
Dallas, TX.
Purpose: Esotropia is a common form of childhood strabismus,
but there are few data on effects on health related quality of life
(HRQOL) in children with esotropia. As part of a larger research
effort to develop patient-reported outcome measures for pediatric eye
conditions, we interviewed esotropic children and, as a proxy, one of
their parents.
Methods: 35 children with esotropia (aged 2 to 17 years) were
recruited. Esotropia types were accommodative or partially
accommodative (17; 49%), infantile (7; 20%), non-accommodative
(6; 17%), consecutive (2; 6%), 6th nerve palsy (1; 3%), Duane
syndrome (1; 3%), and mechanical (1; 3%). Individual semistructured interviews were conducted with children aged 5-17 years
(n=23). One parent was also interviewed for each child (for children
<5 years only the parent was interviewed). Transcripts from these
recorded interviews were independently evaluated by 2 investigators
using NVivo software. Specific HRQOL concerns were identified
from both child and parent interviews and coded by assigning to
themes. Discrepancies were resolved by discussion. The frequency of
each theme was calculated.
Results: Overall, 21 themes were identified. From child interviews
(n=23), the top concerns (each mentioned by 18 [78%] of 23) were
Negative Emotions such as feeling bad, scared, or nervous, and
problems related to Treatment (e.g., glasses, patching or atropine).
Vision concerns, including poor vision, poor depth perception,
and double vision were mentioned by 17 children (74%). In proxy
interviews, most frequently mentioned concerns by parents (n=23)
regarding their child’s HRQOL were problems with Treatment (18;
78%), followed by Activities, Sports, or Hobbies (15; 65%), and
Negative Emotions (15; 65%). For children <5 years old where only
the parent proxy interview was conducted (n=12), top concerns
perceived as affecting the child were problems with Treatment (11
[92%] of 12), Negative Emotions (7; 58%), and Discomfort or Ocular
Sensations (7; 58%).
Conclusions: Children with esotropia experience a range of HRQOL
concerns but there are differences according to whether they are
reported by the child themselves or by the parent as a proxy for the
child. Identified concerns will be used to develop child and proxy
HRQOL instruments.
Commercial Relationships: Laura Liebermann, None; David A.
Leske, None; Sarah R. Hatt, None; Yolanda S. Castañeda, None;
Eileen E. Birch, None; Jonathan M. Holmes, None
Support: NIH Grants EY024333 (JMH), EY018810 (JMH), and
EY022313 (EEB), Research to Prevent Blindness, and the Mayo
Foundation.
Program Number: 5206 Poster Board Number: D0211
Presentation Time: 3:45 PM–5:30 PM
The Effects of Pediatric Primary Brain Tumors on Vision and
Quality of Life
Jason Peragallo1, Supharat Jariyakosol1, 2, Beau B. Bruce1, Nancy
J. Newman1, Valerie Biousse1. 1Emory University, Atlanta, GA;
2
Chulalongkorn University, Bangkok, Thailand.
Purpose: Brain tumors are the leading cause of death from childhood
cancer. Improvements in detection, therapy, and surveillance have
improved survival. Permanent sequelae of the tumor and its treatment
may cause severe impairment and reduced quality of life (QOL).
We reviewed the literature and initiated a quality improvement (QI)
project evaluating visual impairment and its effects on QOL.
Methods: Patients ≤18 yo & ≥6 months post primary brain tumor
(PBT) diagnosis, excluding primary intrinsic anterior visual pathway
tumors, underwent neuro-ophthalmologic examination. In the QI
project, patients and parents completed Health-related QOL (HRQOL) [PedsQL Brain Tumor Module] and Vision-related QOL
(VR-QOL) questionnaires [children <8yo: Children’s Visual Function
Questionnaire; 8-18yo: EYE-Q]. Demographic data, driving status,
schooling, and use of low-vision aids were recorded. Patients were
classified as normal, visually impaired, or legally blind. We reviewed
recent studies (2000-2014) of ophthalmologic sequelae, long-term
disability, and QOL in pediatric PBT patients.
Results: 32 PBT patients were evaluated (24 supra-, 8 infratentorial). 3/32 (9.3%) were legally blind; 15/32(46.9%) had visual
impairment; 15/31(48.4%) had significant visual field defects,
16/32(50%) had strabismus, cranial nerve palsies, or nystagmus.
Patients’ median HR-QOL was 68.6 (range 28.1-95.8). Parents’ HRQOL scores for their children were 0.82x (SE±0.25) their children’s
score(R2=0.59;p<0.001). VR-QOL median score was 3.35 (range
0.38-4.0). HR-QOL scores were not significantly correlated with
visual function. EYE-Q was -3.0 points lower (SE±0.64;p<0.001)
in those with severe visual impairment vs. those with none. Twelve
studies met our criteria for review. Prevalence of visual dysfunction
ranged from 8-79%. 3/12 studies reported frequency of bilateral
blindness (3-16%). HR-QOL was significantly lower in PBT patients
compared to normal controls in most studies. VR-QOL was not
addressed in recent pediatric PBT studies.
Conclusions: Children with PBT and their parents have similar
perceptions of HR-QOL. VR-QOL loss was associated with visual
dysfunction in PBT patients in our center’s experience. “Cured”
pediatric PBT patients may have severely affected vision, HR-QOL,
and VR-QOL. Systematic neuro-ophthalmologic examinations of
pediatric PBT patients may improve long-term visual outcomes and
QOL through earlier intervention.
Commercial Relationships: Jason Peragallo, None; Supharat
Jariyakosol, None; Beau B. Bruce, None; Nancy J. Newman,
None; Valerie Biousse, None
Support: Supported in part by an unrestricted departmental
grant (Department of Ophthalmology) from Research to Prevent
Blindness, Inc., New York, and by NIH/NEI core grant P30-EY06360
(Department of Ophthalmology). Dr. Jariyakosol receives support
from Chulalongkorn University (Bangkok, Thailand). Dr. Bruce
receives research support from the NIH/NEI (K23-EY019341). Dr.
Newman is a recipient of the Research to Prevent Blindness Lew R.
Wasserman Merit Award.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 5207 Poster Board Number: D0212
Presentation Time: 3:45 PM–5:30 PM
Association of Specific Symptoms with Reduced Health-Related
Quality of Life in Children with Intermittent Exotropia
David A. Leske, Sarah R. Hatt, Laura Liebermann, Jonathan M.
Holmes. Ophthalmology, Mayo Clinic, Rochester, MN.
Purpose: To evaluate the relationship of specific intermittent
exotropia (IXT) symptoms with health-related quality of life
(HRQOL) in children with IXT and their parents.
Methods: The Intermittent Exotropia Questionnaire (IXTQ) was
administered to a cohort of 35 children (aged 5-13 years) with IXT,
without previous surgery, and their parents (Child, Proxy, Parent
Psychosocial, Parent Function, and Parent Surgery subscales). All
IXTQ questionnaires were Rasch scored using an established lookup table and converted to a 0-100 scale. Children also completed
a 22-item symptom survey, rating symptoms as “not at all,”
“sometimes,” or “a lot” for 5- to 7-year olds, or “never,” ‘almost
never,” “sometimes,” “often,” or “almost always” for 8- to 17-year
olds, yielding a score of 0 to 4 per item. Relationships between
IXTQ scores and symptom scores were analyzed by univariate linear
regression, and symptoms associated with poor HRQOL (P≤ 0.1)
were fit to a stepwise multivariate linear regression model.
Results: Lower (worse) Child IXTQ HRQOL scores were associated
with symptoms of difficulty focusing eyes (P=0.0007), double
vision (P=0.007), eyes hurting (P=0.006), and problems with eyes
in the sun (P=0.06)(model r-square=0.64). Lower Proxy IXTQ
scores were associated with child symptoms of eyes feeling funny
(P=0.02) and eyes going in and out (P=0.06)(model r-square=0.27).
Parent Psychosocial IXTQ scores were associated with eyes going
in and out (P=0.02) and difficulty staring at things (P=0.03)(model
r-square=0.23). Parent Function IXTQ scores were only associated
with symptoms of eyes going in and out (P=0.04)(model r-square
0.12). No relationships were found between child symptoms and
Parent Surgery IXTQ scores.
Conclusions: In Children with IXT, reduced child HRQOL is
predicted by the specific symptoms of difficulty focusing eyes,
double vision, eye pain, and problems with eyes in the sun. In
contrast to child HRQOL, poor proxy or parental HRQOL are less
explained by child symptoms, but are associated with the child
experiencing symptoms of the eyes going in and out, eyes feeling
funny, and difficulty staring at things. For clinical and research
applications, a revised shortened symptom survey could be based on
the questions we found to be associated with reduced HRQOL.
Commercial Relationships: David A. Leske, None; Sarah R. Hatt,
None; Laura Liebermann, None; Jonathan M. Holmes, None
Support: NIH Grants EY024333 (JMH) and EY018810 (JMH),
Research to Prevent Blindness, and the Mayo Foundation.
Program Number: 5208 Poster Board Number: D0213
Presentation Time: 3:45 PM–5:30 PM
Vision In Preschoolers - Hyperopia In Preschoolers (VIP - HIP)
Study: Effect of Uncorrected Hyperopia on Early Literacy
Marjean T. Kulp. College of Optometry, Ohio State University,
Columbus, OH.
Purpose: To determine whether uncorrected hyperopic (≥3 to
≤6 diopters (D)) 4- or 5-year-old children without strabismus or
amblyopia perform worse on an assessment of literacy (Test of
Preschool Early Literacy [TOPEL]) than comparable emmetropic
children.
Methods: Children aged 4 or 5 who were attending preschool
or kindergarten and who had not previously worn correction for
refractive error were enrolled. Children with an Individualized
Education Program (IEP) for development, educational, or behavioral
issues were excluded. Vision examination with cycloplegic refraction
was performed to confirm the presence of either hyperopia (≥3.0D
to ≤6.0D in the most hyperopic meridian of at least one eye with
astigmatism ≤1.5D and anisometropia ≤1.0D) or emmetropia
(hyperopia ≤1.0D, astigmatism <1.0D, anisometropia <1.0D, and
myopia <1.0D). Threshold visual acuity and cover testing were
performed to rule out presence of amblyopia or strabismus. The
TOPEL, composed of Print Knowledge, Definitional Vocabulary,
and Phonological Awareness subtests, was administered by trained
examiners.
Results: Four hundred ninety-two children (244 hyperopes and
248 emmetropes) participated (mean age 58 months; mean±SD
spherical equivalent refractive error +3.47D±0.81 in hyperopes
and +0.37D±0.50 in emmetropes). The majority of children (89%)
were in Head Start. The overall mean±SD TOPEL raw score
was 86.6±23.2. The mean TOPEL score in hyperopic children
was significantly lower than in emmetropic children (-5.9, 95%
confidence interval [-10.0, -1.8], p=0.005). After adjustment for age,
race/ethnicity, and parent/caregiver’s education the mean difference
between hyperopes and emmetropes was -4.3 (-7.7, -0.89),(p=0.01)
for TOPEL overall,-2.4 (-4.1, -0.6), (p=0.007) for Print Knowledge,
-1.6 (-3.3, 0.2), (p=0.08) for Definitional Vocabulary, and -0.3
(-1.1, 0.4), (p=0.39) for Phonological Awareness. For children with
moderate hyperopia (+3.0 to 6.0D), the magnitude of hyperopia was
not related to the TOPEL score (p=0.75).
Conclusions: Uncorrected hyperopia in 4- to 5-year-old children
enrolled in preschool or kindergarten is associated with significantly
worse performance on a test of early literacy (TOPEL). In addition
to remedial educational intervention, these children may benefit from
preventive correction of refractive error, however, the effect of this
intervention has not yet been evaluated.
Commercial Relationships: Marjean T. Kulp, None
Support: NIH/NEI R01EY021141
Program Number: 5209 Poster Board Number: D0214
Presentation Time: 3:45 PM–5:30 PM
Disinvestment of population-wide eye screening at age 14-24
months in the Netherlands
Frea Sloot1, Aya Sami1, 2, Hatice Karaman2, 1, Sjoukje E. Loudon1,
Janine Benjamins3, Hein Raat4, Huibert J. Simonsz1. 1Ophthalmology,
Erasmus Medical Center, Rotterdam, Netherlands; 2Orthoptics,
University of Applied Sciences, Utrecht, Netherlands; 3Public Health
Service Icare, Meppel, Netherlands; 4Public Health, Erasmus Medical
Center, Rotterdam, Netherlands.
Purpose: Dutch children are eye-screened 7 times at Child Health
Care Centers that screen 97% of all children for general health
disorders. Omission of eye screening at age 6-9 months (ARVO
2014) did not seem to reduce referrals and detection of amblyopia;
referral was based mostly on conspicuous strabismus noted by
parents or screening physicians. We now assessed the screening
examinations at age 14 and 24 months.
Methods: Preverbal screening (cover test, Hirschberg test, eye
movements, cornea and pupillary reflexes) was omitted in the second
of two sequential birth cohorts. All children were screened at 1-2
and 3-4 months, but at 14 and 24 months only children in the control
group (born July-December 2011) were eye screened. Children in the
intervention group (born January-June 2012) did attend consultations
for all other basic screening and vaccinations, but eye screening, was
performed only in case of positive family history, something noted
by the parents or a visually apparent eye disorder. Data was collected
from screening records, anonymous questionnaires and on-site
observations.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Results: 112 out of 6188 children (1.8%) in the control group and 76
out of 5623 children (1.4%) in the intervention group were referred to
an orthoptist or ophthalmologist. Visually apparent eye disorders or
conspicuous strabismus noted by the parents or screening physician
led to referral in 79 children (1.3%) versus 66 children (1.2%).
Twenty-seven children in the control and six in the intervention
group were referred because of specific eye screening. The latter
six children were examined because of a positive family history (1),
smaller eye (1) or for unknown reasons (4). In the questionnaires
screening physicians had indicated that they found examination of
children at age 14-24 months difficult, especially the cover test.
During the observations, cover test, motility and pupillary reflexes
were not always performed correctly. Hirschberg test was almost
always performed correctly.
Conclusions: At the age of 14-24 months most children are
referred because of a visually apparent eye disorder or conspicuous
strabismus. Although still a minority, specific eye screening led to
more referrals at the age of 14-24 months than at 6-9 months.
Commercial Relationships: Frea Sloot, None; Aya Sami, None;
Hatice Karaman, None; Sjoukje E. Loudon, None; Janine
Benjamins, None; Hein Raat, None; Huibert J. Simonsz, None
Clinical Trial: NCT01675193
Program Number: 5210 Poster Board Number: D0215
Presentation Time: 3:45 PM–5:30 PM
Symptoms in Children with Intermittent Exotropia
Sarah R. Hatt, David A. Leske, Laura Liebermann, Jonathan M.
Holmes. Ophthalmology, Mayo Clinic, Rochester, MN.
Purpose: Children with intermittent exotropia (XT) may experience
symptoms related to their eye condition. Nevertheless, the frequency
and type of symptoms have not been rigorously studied. The aim
of this study was to identify the types of symptoms experienced by
children with intermittent XT and to report their frequency.
Methods: 24 children (aged 5 to 17 years) with intermittent XT
underwent individual semi-structured interviews to elicit concerns
related to their eyes. Interview transcripts were reviewed and specific
symptoms identified. Based on the interview transcripts, 22 specific
symptom questions were formulated and compiled as a symptoms
questionnaire. Symptom questionnaires were then administered to a
separate cohort of 35 children (aged 5-13 years) with intermittent XT,
who had not undergone previous surgery. Response options were:
“not at all”, “sometimes” or “a lot” (5-to 7-year olds) or “never”,
‘almost never”, “sometimes”, “often” or “almost always” (8- to 17year olds). For analysis purposes, responses of “not at all”, “never”
or “almost never” were considered consistent with not having the
symptom. The overall frequency of symptoms was then calculated.
Results: The mean number of specific symptoms reported by each
child was 7 (range 2 to 19). The most frequently reported symptom
was rubbing the eyes (29 [83%] of 35), followed by problems with
eyes in the sun (22, 63%), the eyes feeling tired (22, 63%), having
to shut one eye (17, 49%), awareness of panoramic vision (17, 49%)
and having to blink to control the eyes (15, 43%).
Conclusions: Children with intermittent XT frequently report
symptoms such as having to rub their eyes and having problems with
their eyes in the sun. Results from this study could be used to develop
a shorter symptom survey for children with intermittent XT. Formal
assessment of symptoms may be important for understanding how
intermittent XT affects children and for optimizing management.
Commercial Relationships: Sarah R. Hatt, None; David A. Leske,
None; Laura Liebermann, None; Jonathan M. Holmes, None
Support: NIH Grants EY024333 (JMH) and EY018810 (JMH),
Research to Prevent Blindness, and the Mayo Foundation.
Program Number: 5211 Poster Board Number: D0216
Presentation Time: 3:45 PM–5:30 PM
True Congenital Esotropia
Anthony Manassero1, Marie-Andrée Espinasse-Berrod1, PierreAntoine Aymard1, 2, Charlotte Creux1, 2, Matthieu Robert1, 2.
1
Ophthalmology, Necker Hospital, Paris, France; 2Université Paris
Descartes, Paris, France.
Purpose: Classically, “congenital esotropia” designated “early-onset
esotropia”. The latter replaced the former as esotropia is virtually
never seen at birth but appears over the first months of life. In rare
instances, however, true constant esotropia is said to be seen at birth.
Only then, when seen in the very first days of life, could it be called
true congenital esotropia (CE). Here we tested the hypothesis that
CE does exist and that it is a radically distinct entity from early-onset
esotropia.
Methods: Retrospective study of all cases of neonates referred to
the pediatric neuro-ophthalmology clinic between October 2010 and
2014 for a constant esotropia seen at birth and formally assessed. In
addition to follow-up appointments and systematic complete general
pediatric examination, two systematic ophthalmologic examinations
were achieved: the first one within the three first weeks of life looked
for prenatal and perinatal history, an ophthalmologic malformation,
and any associated pathology; it assessed the diagnosis and the nature
of esotropia; the last one at 8 months included an ophthalmologic and
an orthoptist examination assessing visual function, binocular vision
(Lang test) and esotropia evolution.
Results: Ten patients were included. Among them, 70% of patients
had a franc abduction limitation of the right eye and 30% of the
left eye. Esotropia regressed completely in 9/10 cases. The median
time of disappearance was 4 weeks (3 – 9 weeks). The patient who
did not have a complete regression was subsequently diagnosed as
Duane retraction syndrome (DRS). There was no consanguinity, no
prematurity among these patients; four had had a difficult delivery:
two needed instrumental delivery (forceps), one was a breech
delivery, and one had a wrapped umbilical cord. One patient had a
prenatal history of toxoplasmosis seroconversion at three months that
had resulted in a treatment (Spiramycin). No patient had any sign of
amblyopia and all had a positive Lang test.
Conclusions: True CE does exist and can be defined as a constant
esotropia in a healthy newborn with a complete spontaneous
regression in 100% of cases. The clinical characteristics and
evolution of true CE are the ones of a congenital abducens nerve
palsy, which would regress early enough to allow for a realignment
of the visual axes during the critical period for visual development.
It would therefore result in orthophoria with normal retinal
correspondence, as opposed to early-onset esotropia.
Commercial Relationships: Anthony Manassero, None; MarieAndrée Espinasse-Berrod, None; Pierre-Antoine Aymard, None;
Charlotte Creux, None; Matthieu Robert, None
Program Number: 5212 Poster Board Number: D0217
Presentation Time: 3:45 PM–5:30 PM
Preliminary Evaluation of a Mobile App for Strabismus
Screening
Shrinivas Pundlik1, Matteo Tomasi1, 2, Kevin Houston1, Gang
Luo1. 1Ophthalmology, Harvard Medical School, Schepens Eye
Research Institute, Mass Eye and Ear, Boston, MA; 2EyePhone LLC,
Cambridge, MA.
Purpose: An automated Hirschberg Test using photographic analysis
of the corneal reflection has been suggested as a method to screen
for strabismus. However, cost to develop and maintain a dedicated
device can hinder accessibility. Smartphones offer a platform to
dispense inexpensive and widely accessible eye-care solutions.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
We have developed a mobile app with the goals of obtaining rapid,
convenient, and quantifiable strabismus measurements. We present
the results of a preliminary evaluation experiment to determine the
accuracy of the app.
Methods: When using the app, an examiner asks the patient to
fixate at a particular point and simply points the phone camera to
the patient’s face. Real time eye detection is shown on the screen,
after which a snapshot can be taken with the flash on. The app then
localizes the iris center, the corneal reflection, and computes the eye
deviation according to the offset of the corneal reflection from the
iris center. To evaluate the accuracy of the app, four subjects without
strabismus fixated binocularly at 11 points at various eccentricities
from -5.8° to 5.8° (a total of about 20Δ range). Eye deviations with
respect to the center point (0°) were computed for the left and right
eyes separately, and compared with the ground truth. In a case study,
one subject with known left exotropia was tested with the cover test
and by the app. In this case, the app measured the difference in the
deviations of the two eyes.
Results: The app measurements for the 8 eyes closely matched the
ground truth, with a slight over estimation (line fitting slope=1.08,
R2=0.99). The mean measurement error was 1.1 ± 0.9Δ.There was
no difference between right and left eyes (p=0.18). In case of the
patient with known strabismus, the cover test and the app found left
exotropia of 24 ± 3.6Δ and 28.5 ± 3.5Δ, respectively.
Conclusions: Preliminary results indicate that the strabismus app can
accurately measure a wide range eye deviations and further clinical
testing of the app is warranted.
Strabismus Measurement App. Before image capture the display
shows the area of interest (green box) and detected eyes (red).
Strabismus Measurement App. After image capture the display shows
the iris detection, corneal reflection, and the computed eye deviation
values.
Commercial Relationships: Shrinivas Pundlik, None; Matteo
Tomasi, EyePhone LLC (I); Kevin Houston, EyePhone LLC (I);
Gang Luo, EyePhone LLC (I)
Program Number: 5213 Poster Board Number: D0218
Presentation Time: 3:45 PM–5:30 PM
Development of 3D mouse-assisted Hess-Lancaster test
Jong-Mo Seo1, 2, Min-Won Seo2, So Hyun Bae4, 2, Hee-Kyung
Yang3, Jeong-Min Hwang1, 3. 1Ophthalmology, Seoul National
University, Seoul, Korea (the Republic of); 2Electrical and Computer
Engineering, Seoul National University, Seoul, Korea (the Republic
of); 3Ophthalmology, Seoul National University Bundang Hospital,
Seongnam-si, Korea (the Republic of); 4Ophthalmology, Kangnam
Sacred Heart Hospital, Seoul, Korea (the Republic of).
Purpose: Traditional Hess-Lancaster test uses nine points for
diagnosing which part of the ocular muscle is paralyzed, and it
uses red/green glass lenses for the inhibition of binocular fusion
mechanism. This method is simple and easy to follow, but the manual
examination and charting of the result decreases the reproducibility.
Computerized test has been developed, but using joystick, mouse and
keyboard are not so much intuitive as using pointer. To enhance the
user interface and the fidelity of the computer-based test, 3D mouse
was adopted and the target was revised.
Methods: The software was developed on Windows 7 operating
system with Application Programming Interface. And for
the interactive and efficient test, 3D mouse (SpaceNavigator,
3Dconnection Inc.) was adopted. Nine reference points for the test
are equally separated in distance, and the sequence of the test point
is determined in pseudo-random manner, thus all points will be
evaluated without duplication. Evaluation point will be displayed
with empty circle with the color of red or green as a reference. And
around this circle, the opposite color pair, green or red empty circle is
displayed as a mobile target, so the patient should control 3D mouse
in x- or y-direction to overlap the mobile circle onto the reference
circle. This result reflects the deviation angle according to the gaze.
On confirming the position of the second circle by clicking, reference
circle will be changed to vertical bar, and the mobile circle will be
changed to rotated bar, so the patient should rotate mobile bar until
it is aligned to the reference bar by rotating 3D mouse. This result
reflects the deviation of torsion on each gaze. By this way, all points
were evaluated in terms of deviation angle and torsion.
Results: 18 points of pseudo-random sequence evaluation (9 points
for each eye) prevented the patient to notice which eye is being tested
or which point will be displayed next time. This reduces the patient’s
cheating for secondary gain. By separating circle matching and bar
matching, patient’s attention can be increased in each sequence test.
And by using 3D mouse, all interactions were integrated into single
interface which can be used easily by the examinee.
Conclusions: By using 3D mouse and the variable target,
computerized Hess-Lancaster test was developed. This test might
enhance the performance and the reliability of the computer-based
clinical evaluation of the paralytic strabismus.
Commercial Relationships: Jong-Mo Seo, None; Min-Won Seo,
None; So Hyun Bae, None; Hee-Kyung Yang, None; Jeong-Min
Hwang, None
Support: MSIP (Ministry of Science, ICT & Future Planning), Korea
in the ICT R&D program 2014, Public Welfare and Safety Program
2010-0020851 by MEST
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 5214 Poster Board Number: D0219
Presentation Time: 3:45 PM–5:30 PM
Spasmus nutans often reveals an underlying, potentially severe,
disease
Gilles Martin1, Alexandra Gavard-Perret1, Olivia Zambrowski1,
Isabelle Ingster-Moati1, Nathalie Boddaert1, Pierre-Paul Vidal2,
Matthieu Robert1, 2. 1Hôpital Universitaire Necker-Enfants Malades,
APHP, Paris, France; 2COGNAC-G, Université Paris-Descartes,
Sorbonne Paris Cité, Paris, France.
Purpose: Spasmus nutans is a type of nystagmus that has been
known for years to be benign, while recent studies have shown that
it sometimes reveals serious neurological or retinal disease. We
tested the hypothesis that spasmus nutans is most often not benign
and idiopathic. We performed a retrospective, observational study to
better understand the conditions associated with spasmus nutans-type
nystagmus, as well as the incidence of these conditions.
Methods: Children referred to the neuro-ophthalmology clinic
between November 1, 2009 and November 1, 2014, for a spasmus
nutans and having benefitted from a systematic work-up were
retrospectively reviewed. Spasmus nutans was defined as a
pendular nystagmus with a high beating frequency (>5Hz), a small
amplitude and a phase dissociation between the two eyes. It could
be intermittent, horizontal, vertical, torsional or multidirectional
and dissociated to the extent of being purely monocular. It could be
associated with head tilt or head nodding. The work-up included
neuro-ophthalmological examination with dilated fundus, recording
of the nystagmus (video, eye tracking with a child-friendly dedicated
infrared photo-reflectometry eye tracker, Ober Consulting®, Poland,
when possible) cerebral imaging (MRI-scan) and electroretinography
(Metrovision®, France). Cases with incomplete investigations, cases
with already known diagnosis and also incidentally presenting a
spasmus nutans and cases with obvious associated photophobia at the
first visit were excluded. The combination of these data allowed us
to classify each case in one of three groups of categories of spasmus
nutans (revealing a neurological disease, revealing a retinal disease,
or idiopathic) and to compare their relative proportions.
Results: Thirty-two children (19 males) were included. The
nystagmus had been noticed at a median age of 5 months. In 53% of
cases (n=17), it led to the diagnosis of another condition. Most often
a neurological disease was diagnosed (34%, n=11) such as chiasmal
gliomas (22%, n=7), while 13% (n=4) of the children exhibited a
retinal dysfunction. In 47% (n=15) of cases, spasmus nutans was
considered benign idiopathic.
Conclusions: In this study, spasmus nutans-type nystagmus was, in
the majority of cases, the revealing symptom of another disease, often
severe, and not a benign clinical entity. A systematic work-up should
be considered in any case of a child who presents with spasmus
nutans.
Commercial Relationships: Gilles Martin, None; Alexandra
Gavard-Perret, None; Olivia Zambrowski, None; Isabelle IngsterMoati, None; Nathalie Boddaert, None; Pierre-Paul Vidal, None;
Matthieu Robert, None
Program Number: 5215 Poster Board Number: D0220
Presentation Time: 3:45 PM–5:30 PM
Spasmus nutans: an analysis of systemic and ocular comorbidities
Nechama Shoshani2, 1, Sylvia Kodsi2, 3, Steven E. Rubin2, 3.
1
Ophthalmology, Montefiore Medical Center, New York, NY;
2
Ophthalmology, NS-LIJ Medical Center, Long Island, NY; 3Hofstra
University, Long Island, NY.
Purpose: Spasmus nutans has often been described as a benign, selflimited disorder of childhood, yet case studies have reported systemic
comorbidities in children presenting with this disorder. Previous
studies have not evaluated the systemic comorbidities associated
with the classic triad of nystagmus, head nodding and torticollis.
We performed a retrospective chart review to evaluate whether this
disorder is truly benign and self-limited.
Methods: We reviewed the charts of all pediatric patients who were
diagnosed with nystagmus at the pediatric ophthalmology center of a
tertiary care center during the years of 2004-2014. Inclusion criteria
required that the patient present with nystagmus and head nodding
and/or torticollis. 20 patients were identified. Patient characteristics,
and information related to age, gender, vision, refraction, strabismus,
amblyopia, neuroimaging, and ocular and systemic comorbidities
were recorded.
Results: Initial vision was found to be reduced in one or both eyes
in 30% of patients, and final vision in 47%. 55% of patients had
refractive errors requiring glasses wear. 50% had amblyopia, and
50% had strabismus. There were findings on brain MRI in 5 of 15
patients for whom MRI was available; these included one each of
CNS tumor, poorly formed corpus callosum, and benign external
hydrocephalus, and two others with benign external hydrocephalus
vs. volume loss. Systemic disease was present in 50%; these children
all had a systemic disorder that could account for their nystagmus.
Developmental delay was present in 40%. Overall, 14 of the 20
children (70%) had ocular, neurologic, or systemic comorbidities
aside from amblyopia and strabismus. We also found there to be no
resolution of nystagmus in 8 of 14 patients (57%) with last visit at
age 45 months or greater (mean age 85 months); however 63% of
those patients with unresolved nystagmus did have resolution of their
head nodding and torticollis.
Conclusions: In the majority of children presenting with the triad
of spasmus nutans, the disorder does not appear to be an isolated
entity, but carries serious visual and systemic implications. Given
the number of patients with continuing nystagmus and underlying
diagnoses, the description of spasmus nutans as a benign, self-limited
entity may be inaccurate. We recommend that children presenting
with features of spasmus nutans be evaluated carefully for underlying
ocular, intracranial, and systemic abnormalities.
Commercial Relationships: Nechama Shoshani, None; Sylvia
Kodsi, None; Steven E. Rubin, None
Program Number: 5216 Poster Board Number: D0221
Presentation Time: 3:45 PM–5:30 PM
Regression of inferior oblique recession for unilateral congenital
and acquired superior oblique palsy: 10 year review
Hachemi NEZZAR4, 1, Helene DALENS1, Florian FARGUETTE1,
Frederic CHIAMBARETTA1, Joyce MBEKEANI2, 3. 1ophthalmology,
Auvergne University Hospital, Clermont Ferrand, France;
2
department of Surgery, North Bronx Health Network, New York,
NY; 3ophthalmology and visual Science, Albert Einstein College of
Medecine, New York, NY; 4king Faisal Hospital and Research Center,
Riyadh, Saudi Arabia.
Purpose: The superior oblique (SO) palsy is the most common
isolated paralytic strabismus and the inferior oblique recession is one
of the surgical techniques employed for managing this palsy.The aim
of our study was to evaluate the long term efficacy of inferior oblique
recession for the management of vertical deviation in congenital and
acquired SO palsy
Methods: This study is a retrospective chart review of 62 patients
with congenital and acquired superior oblique palsy managed
with inferior oblique recession. All patients were operated at the
University Hospital of Clermont-Ferrand between 1999 and 2010.
Demographic analysis was conducted on all 62 patients. Forty–four
patients submitted to final full ophthalmic and orthoptic assessment
for this study and were analyzed for post-operative results. All
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
measurements were performed using Maddox rod tests. Vertical,
horizontal and cyclotortion measurements were taken pre and postoperatively, but only vertical deviations were evaluated for this study.
Several criteria were considered: the first criterion was the initial
angle of vertical deviation in primary gaze and the second was the
angle of deviation in three postoperative periods: period (1) up to 2
years, period (2) between 2 and 5 years and period (3) more than 5
years. Quantitative data were analyzed using Student T and MannWhitney U tests and multiple groups were compared using ANOVA
and Tukey Kramer tests
Results: Women accounted for 41.9% of patients and men, 58.1%.
The mean age of all patients when operated was 29.57years.
Congenital SO palsy cases were 83.9% while 16.1% were acquired.
The initial mean deviation in primary gaze position was 14.55 (± 8.2)
dioptres. The average post-operative decrease in vertical deviations
was by 11.6 dioptres for distance and by 9.95 dioptres for near.
Surgical efficacy for vertical deviation correction at distance was
90.2% at 2 years, 76.9% between 2 to 5 years and 62% after 5 years.
No significant difference in deviations was found when the initial
deviations were greater than 25 dioptres
Conclusions: Our study confirms the efficacy of inferior oblique
recession for management of congenital and acquired superior
oblique palsy and documents regression of results over time. To our
knowledge this is the first study to show this decline in efficacy after
5 years of follow up
Commercial Relationships: Hachemi NEZZAR, None; Helene
DALENS, None; Florian FARGUETTE, None; Frederic
CHIAMBARETTA, None; Joyce MBEKEANI, None
Program Number: 5217 Poster Board Number: D0222
Presentation Time: 3:45 PM–5:30 PM
Botulinum Toxin-Augmented Strabismus Surgery versus
Conventional Surgery in the Treatment of Large-Angle Infantile
Esotropia
Aubrey Gilbert1, 2, Michael J. Wan2, Melanie Kazlas2, 1, Carolyn Wu2,
David G. Hunter2, Iason Mantagos2, Ankoor Shah2. 1Ophthalmology,
Massachusetts Eye and Ear Infirmary, Boston, MA; 2Ophthalmology,
Boston Children’s Hospital and Harvard Medical School, Boston,
MA.
Purpose: The treatment of large-angle infantile esotropia remains
a challenge. Surgical treatment traditionally has involved either
three-muscle surgery or supra-maximal medial rectus recessions, but
both methods have significant drawbacks including risk of over- or
undercorrection. An alternative is to use botulinum toxin to weaken
the medial rectus muscles, but multiple treatments are often required
and the success rate for large deviations is poor. It has been suggested
that the best approach may be to combine these treatments. No
previous study has directly compared botulinum toxin-augmented
surgery to conventional surgery alone.
Methods: A retrospective, comparative study was completed
evaluating baseline characteristics and outcomes of consecutive
patients with large-angle infantile esotropia (55 prism diopters(Δ) or
greater) who underwent either conventional or botulinum toxinaugmented strabismus surgery. The primary outcome measure was
post-operative deviation and need for retreatment within one year of
initial intervention. Success was defined as a deviation <10Δ and no
retreatment at 1 year after the initial intervention.
Results: The record review identified 38 patients meeting inclusion
criteria, of whom 14 had been treated with botulinum toxinaugmented surgery and 24 with bilateral medial rectus recessions.
Prior to surgery, the augmented group had a larger median angle of
deviation (65 versus 60Δ, p = 0.006) and less recession of the medial
rectus muscles was performed (5.5 versus 6.0 mm, p = 0.005). The
augmented group had greater success at 1 year (70% versus 30%, p =
0.035). The augmented group also had a significantly smaller median
angle of deviation at 1 year (0 versus 18Δ, p = 0.026). There were no
serious complications in either group.
Conclusions: Botulinum toxin can significantly augment the effect
of medial rectus recessions and improve the success of strabismus
surgery in patients with large-angle infantile esotropia.
Commercial Relationships: Aubrey Gilbert, None; Michael J.
Wan, None; Melanie Kazlas, None; Carolyn Wu, None; David G.
Hunter, None; Iason Mantagos, None; Ankoor Shah, None
Program Number: 5218 Poster Board Number: D0223
Presentation Time: 3:45 PM–5:30 PM
Effect of Superior Oblique Posterior 7/8ths Tenectomy on
Anomalous Head Positioning in Patients with Brown Syndrome
Meredith H. Remmer1, Milan P. Ranka1, 2, Mark A. Steele1, 2.
1
Ophthalmology, NYU School of Medicine, New York, NY;
2
Pediatric Ophthalmic Consultants, New York, NY.
Purpose: Brown Syndrome, or superior oblique (SO) tendon sheath
syndrome, is characterized by overaction of the SO tendon, seen
clinically as a restriction of elevation above midline in adduction.
Surgical management is necessary in patients who demonstrate a
significant vertical deviation in primary gaze or an anomalous head
positioning (AHP) in order to maintain binocular fusion. Classical
treatment includes complete SO tenectomy, recession, and spacer
tenotomy. These procedures are limited by inconsistent results
including scarring, under-elevation in adduction and persistent
diplopia. The use of SO posterior 7/8ths tenectomy has shown to
be effective in minimizing complications such as loss of torsional
function and SO palsy. The purpose of this study is to evaluate the
effect of SO posterior 7/8ths tenectomy on AHP in patients with
Brown Syndrome.
Methods: Retrospective chart review was conducted from 2003 to
2014 for patients with Brown Syndrome and an anomalous head
positioning who underwent ipsilateral SO posterior 7/8ths tenectomy.
Brown Syndrome was confirmed intra-operatively through forced
duction testing.
Results: A total of 8 patients (3 male) met inclusion criteria. The
mean age at surgery was 43 +/- 21 months (median 37, range 17 to
79 months). Of the 8 patients, 6 had simultaneous horizontal muscle
surgery. All had SO overaction with the inability to elevate past
midline in adduction.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Mean pre-operative vertical deviation in primary gaze was 6.4 prism
diopters (PD) +/- 4.4, range 2 to 16 PD.
At the most recent postoperative visit, 6 patients (75%) had complete
resolution of their AHP (5 following initial surgery and 1 following
reoperation). Two patients had mild persistent AHP, but were
improved from preoperative evaluation. No patient had restored
elevation past midline in adduction.
Mean post-operative vertical deviation in primary gaze was 1.0 PD
+/- 2.8. (p <0.01)
Average post-operative follow-up was 32 months. No surgical
complications were noted.
Conclusions: Our study demonstrates that SO posterior 7/8ths
tenectomy is an effective procedure for improving both AHP and
vertical deviation in primary gaze in Brown syndrome. All patients
improved from their initial AHP. This approach should be considered
to potentiate binocular fusion in these patients.
SO Posterior Tenectomy A. Isolated SO tendon B. Posterior
tenectomy C. Remaining anterior 1/8 tendon
Commercial Relationships: Meredith H. Remmer, None; Milan P.
Ranka, None; Mark A. Steele, None
Program Number: 5219 Poster Board Number: D0224
Presentation Time: 3:45 PM–5:30 PM
Role of Strabismus Surgery in the Treatment of Adult-Onset
Esotropia
Sara Grace, Kara M. Cavuoto, Hilda Capo, Wei Shi. Ophthalmology,
Bascom Palmer Eye Institute, Miami, FL.
Purpose: Our study aims to describe a large cohort of patients with
adult-onset esotropia of diverse etiologies in terms of their presurgical characteristics, operative data and surgical outcomes.
Methods: A retrospective chart review was conducted for 249
patients that underwent strabismus surgery for adult-onset esotropia
within the past 15 years at a large academic center. Primary outcome
measures were resolution of diplopia and a deviation less than 10 PD
at distance and near in primary position.
Results: Mean age at esotropia diagnosis was 52 years (18-87). The
most common diagnosis overall was cranial nerve six palsy (36%),
followed by thyroid eye disease (18%) and divergence insufficiency
(15%). Pre-operative diplopia was experienced in 94% of patients.
Approximately half (46%) of patients utilized prism preoperatively,
and 13% had undergone prior strabismus surgery for adult-onset
esotropia. Adjustable sutures were employed in 79%, with onethird adjusted on the day of surgery. At 2 months post-operatively,
79.4% and 82.9% of patients measured ≤ 10 PD at distance
and near, respectively. At 2 months post-operatively, significant
differences in resolution of diplopia were found across all diagnoses
for the unilateral recess/resect procedure and the vertical muscle
transposition procedure. At last visit, there was not a significant
difference in diplopia resolution for all diagnoses between all
surgeries. Non-significant differences were seen in dose-effects per 1
mm of surgery across the three main diagnoses.
Conclusions: Multiple surgical approaches yielded successful results.
To determine if significant differences exist for specific surgeries
amongst individual diagnoses, larger subgroups are needed, however
the simple averages for dose effect may suggest this possibility. DI
patients may not follow standard surgical algorithms.
Commercial Relationships: Sara Grace, None; Kara M. Cavuoto,
None; Hilda Capo, None; Wei Shi, None
Program Number: 5220 Poster Board Number: D0225
Presentation Time: 3:45 PM–5:30 PM
Surgical correction of strabismus in monkeys: I. Longitudinal
evaluation of eye alignment and eye movements
Brittany A. Degler1, Mehmet N. Agaoglu1, David K. Coats2, Vallabh
E. Das1. 1College of Optometry, University of Houston, Houston, TX;
2
Ophthalmology, Baylor College of Medicine, Houston, TX.
Purpose: Strabismus surgery is well documented in both the
literature and in practice with varying levels of success and
permanence. Our goal is to characterize longitudinal changes in
eye alignment and movements in monkey models for strabismus
following strabismus correction surgery.
Methods: The study included 1 rhesus monkey (M1) with exotropia.
Strabismus had previously been induced using an optical prismviewing paradigm from birth until 4 months to disrupt binocular
vision during their critical period for visual development. A
recession/resection surgery was performed at 6 years of age to
weaken the lateral rectus and strengthen the medial rectus of the left
eye only. Strabismus angle, saccade performance, smooth pursuit
performance, fixation stability and nystagmus were analyzed before
surgery, immediately (1-3 days) after surgery and 6 months after
surgery. Similar analysis of a second strabismic monkey is planned.
Results: Strabismus angle with the right (untreated) eye viewing
was ~31°XT (pre), ~11°XT (immediate post), ~18°XT (1wk post),
and ~20°XT (6 months post), and with the left eye viewing was
~20°XT, ~10°XT, ~9°XT, and ~18°XT, respectively. Saccade gain
showed significant changes in both eyes when viewing immediately
after surgery, but attained pre-surgical values by 6 months postsurgery. Saccade peak velocity with the left eye viewing increased
immediately after surgery and remained increased after 6 months
in both eyes in both horizontal directions. There were small,
idiosyncratic changes in saccade latency. Smooth pursuit velocity
gain showed significant post-surgical changes in the covered eye,
regardless of which eye was viewing. Naso-temporal asymmetry
during monocular smooth-pursuit increased only with the right eye
viewing immediately after surgery, but attained pre-surgical values by
6 months.
Conclusions: Similar to outcomes in human surgical treatment for
strabismus, strabismus angle in M1 showed a decrease immediately
after surgery, followed by a steady progression back towards
the monkey’s pre-surgery angle. The most notable post-surgical
dynamic change in eye movements was a change in smooth-pursuit
and saccade eye velocity in both the treated and untreated eye.
We hypothesize that these static and dynamic changes are due to
a combination of central neural adaptation and extraocular muscle
remodeling that occurs as a consequence of the surgical procedure.
Commercial Relationships: Brittany A. Degler, None; Mehmet N.
Agaoglu, None; David K. Coats, None; Vallabh E. Das, None
Support: NIH R01 EY022723; P30 EY007551
Program Number: 5221 Poster Board Number: D0226
Presentation Time: 3:45 PM–5:30 PM
Surgical correction of strabismus in monkeys: II. Longitudinal
evaluation of neuronal responses in the Oculomotor nucleus
Mythri Pullela1, Mehmet N. Agaoglu1, Anand C. Joshi1, Sevda
Agaoglu1, David K. Coats2, Vallabh E. Das1. 1College of Optometry,
University of Houston, Houston, TX; 2Opthalmology, Baylor College
of Medicine, Houston, TX.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Purpose: Strabismus surgery is well documented in both the
literature and in practice with varying levels of success and
permanence. Potentially, muscle remodeling and/or central neural
adaptation affects the final state of misalignment after treatment.
Our goal was to assess central adaptation by examining responses of
medial rectus motoneurons (MRMN) in the oculomotor nucleus of
strabismic monkeys following surgical correction.
Methods: The study included one rhesus monkey with an exotropia
(strabismus angle: OD: ~30°, OS: ~15°) that was induced in infancy
using an optical prism-viewing paradigm. Surgical treatment when
animal was ~6years old involved recession of the lateral rectus (LR)
and resection of the medial rectus (MR) of the left eye only. We
recorded from 21 MRMNs prior to treatment and from 70 MRMNs
over the first 6 months following treatment. MRMN firing rates (FR)
and horizontal eye position and velocity acquired during a horizontal
smooth pursuit task (0.3Hz, ±15°) were used to identify regression
coefficients in a first-order model (FR = K*Epos + R*Evel + C). K
and C coefficients were then used to compute the population MR
neuronal drive (ND) necessary to produce static deviation of the nonfixating eye before surgery (pre), <1 month after surgery (post1), ~6
months after surgery (post6).
Results: Strabismus angle (SA) was reduced by ~35% at post1. SA
during OS view gradually increased back to its pre-surgery value
while SA during OD view was still reduced by ~28% of its presurgery value at post6. Analysis of MRMN in the left OMN showed
that the ND to the MR of the treated left eye was decreased although
the strabismus angle was reduced at post1 (pre:67 ±45 sp/s, post1:25
±40 sp/s). Analysis of MRMN in the right OMN indicated that the
ND to the MR of the untreated right eye was increased at post1
(pre:56 ±25spk/s, post1:109 ±42 spks/s). At post6, the ND to both
MR approached pre-surgery values (Lt OMN: 66 ±54 spks/s; Rt
OMN: 44 ±33 spk/s).
Conclusions: The reduced ND to the treated eye at post1 effectively
counters the desired outcome of surgery; post1 increase in ND
to the untreated right eye is consistent with Hering’s law. The
longitudinal (post6) changes in NDs to both treated and untreated
eyes (approaching pre-surgical values) suggest a significant role of
neuronal adaptation in addition to muscle remodeling in setting the
steady-state strabismus angle.
Commercial Relationships: Mythri Pullela, None; Mehmet N.
Agaoglu, None; Anand C. Joshi, None; Sevda Agaoglu, None;
David K. Coats, None; Vallabh E. Das, None
Support: NIH R01 EY022723; P30 EY07551
Program Number: 5222 Poster Board Number: D0227
Presentation Time: 3:45 PM–5:30 PM
Surgical correction of strabismus in monkeys: III. Longitudinal
evaluation of neuronal responses in the Abducens nucleus
Mehmet N. Agaoglu1, 3, Myhtri Pullela1, Anand C. Joshi1, Sevda
Agaoglu1, 3, David K. Coats2, Vallabh E. Das1. 1College of Optometry,
University of Houston, Houston, TX; 2Department of Ophthalmology,
Baylor College of Medicine, Houston, TX; 3Department of Electrical
and Computer Engineering, University of Houston, Houston, TX.
Purpose: Strabismus correction surgery is well documented in both
the literature and in practice with varying levels of success and
permanence. Potentially, muscle remodeling and/or central neural
adaptation affects the final state of misalignment after treatment.
Our goal was to assess central adaptation by examining Abducens
neuron (ABN) responses in strabismic monkeys following surgical
correction.
Methods: The study included one rhesus monkey with an exotropia
(strabismus angle: OD: ~30°, OS: ~15°) that was induced in infancy
using an optical prism-viewing paradigm. Surgical treatment when
animal was ~6years old involved recession of the lateral rectus (LR)
and resection of the medial rectus (MR) of the left eye only. We
recorded from 75 ABNs prior to treatment and from 92 ABNs over
the first 6 months following treatment. ABN firing rates (FR) and
horizontal eye position and velocity acquired during a horizontal
smooth pursuit task (0.3Hz, ±15°) were used to identify regression
coefficients in a first-order model (FR = K*Epos + R*Evel + C). K and
C coefficients were then used to compute the population LR neuronal
drive (ND) necessary to produce static deviation of the non-fixating
eye before surgery (pre), <1 month after surgery (post1), ~6 months
after surgery (post6).
Results: Strabismus angle (SA) was reduced by ~35% at post1. SA
during OS view gradually increased back to its pre-surgery value
while SA during OD view was still reduced by ~28% of its presurgery value at post6. Analysis of Left ABN cells showed that the
ND to the LR of the treated left eye did not change at post1 although
SA was reduced significantly (pre: 177±81 sp/s, post1: 173±79 sp/s).
Analysis of Right ABN cells indicated that the ND to the LR of the
untreated right eye was reduced at post1 (pre: 115±78 sp/s, post1:
80±57). At post6, the ND from Left ABN showed a significant drop
(138±47 sp/s); the ND from Right ABN reverted to pre-surgery levels
(107±26 sp/s).
Conclusions: The unchanged ND to the treated eye immediately after
surgery suggests that alterations in muscle strength of the treated eye
determined the improvement in strabismus angle; post1 reduction
in ND to the untreated eye simply reflects Hering’s law. The post6
changes in the NDs to both treated and untreated eyes suggest a
significant role of neural adaptation in addition to muscle remodeling
in setting the steady-state strabismus angle.
Commercial Relationships: Mehmet N. Agaoglu, None; Myhtri
Pullela, None; Anand C. Joshi, None; Sevda Agaoglu, None; David
K. Coats, None; Vallabh E. Das, None
Support: NIH R01 EY022723; P30 EY07551
Program Number: 5223 Poster Board Number: D0228
Presentation Time: 3:45 PM–5:30 PM
Quantitative measurement of the angle of ocular movements in
patients with horizontal strabismus
Han Woong Lim1, Jung Wook Lee1, Heeyoon Cho1, Yumi Song2, Moon
sang won3, Byung Ro Lee3, Sei yeul oh4. 1Ophthalmology, Hanyang
University Guri Hospital, Guri, Korea (the Republic of); 2Hong
Ik Hospital, Seoul, Korea (the Republic of); 3Hanyang university
hospital, Seoul, Korea (the Republic of); 4Sungkyunkwan university
samsung hospital, Seoul, Korea (the Republic of).
Purpose: To measure the maximum angle of horizontal versions in
patients with comitant horizontal strabismus.
Methods: One hundred two subjects with comitant exotropia
and Fifty-two subjects with comitant esotropia were included.
Photographs were obtained in the cardinal positions of gaze and the
images were processed using Photoshop. The images were analyzed
using the Image J program to measure the angle of version (Fig
1). The maximum angle of horizontal versions (dextoversion and
levoversion) was quantified using a modified limbus test.
Results: The mean angle of adduction (38.1±7.2°) was smaller than
that of abduction (46.6±8.5°) in patients with exotropia (P < 0.001)
(Fig 2). In patients with esotropia, the mean angle of abduction
(45.4±6.3°) was smaller than that of adduction (48.1±8.3°) (P =
0.039). There was a significant negative correlation between the
angle of adduction and the prism diopter of exotropia in patients
with exotropia (R = -0.367, P = 0.001). The angle of abduction and
the prism diopter of esotropia showed no correlation in patients with
esotropia (R = -0.215, P = 0.065).
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Conclusions: The angle of adduction and abduction on horizontal
versions were asymmetric in patients with horizontal strabismus.
These findings suggest that assessment of the angle of ocular
movements is required for better understanding of inequality of the
conjugate eye movements in horizontal strabismus.
Figure 1. Image processing by Photoshop and Image J for
quantitative measurement of the ocular movement. A, Semitransparent image of depression was overlapped with primary
position image using Photoshop. B, The overlapping image was
converted to identify the margin of limbus using Photoshop. C,
Geometrical analysis with Image J showing degrees of ocular rotation
of the limbus.
Figure 2. Case. Composite images as an outcome of overlapping
with the layer of the primary position and processing by Photoshop.
The angle of adduction is lower than that of abduction on both
dextroversion (47.6° vs. 50.8°) and levoversion (35.5° vs. 43.1°) in
this patient.
Commercial Relationships: Han Woong Lim, None; Jung Wook
Lee, None; Heeyoon Cho, None; Yumi Song, None; Moon sang
won, None; Byung Ro Lee, None; Sei yeul oh, None
Program Number: 5224 Poster Board Number: D0229
Presentation Time: 3:45 PM–5:30 PM
Surgical outcomes of exotropia in patients aged under 4 years
Hye Shin Jeon, Jae Ho Jung, Hee-Young Choi. Ophthalmology,
Pusan National university hospital, Busan, Korea (the Republic of).
Purpose: To investigate surgical outcomes in children with
intermittent exotropia who were operated before 4 years old.
Methods: Three hundred forty one patients who had been operated
for intermittent exotropia were included in this study. All of the
patients were followed up for more than 1 year. Pre and post
operative angle of deviation, type of surgery, surgical success rate,
stereopsis at final follow up and factors related to success were
evaluated. Surgical success was defined as binocular deviation was
less than 10 prism diopter(PD) at 1 year after surgery.
Results: Patients were divided into two groups whether operated
before 48 months (younger group) or after 48 months (older group).
Preoperative horizontal deviation was 31.58 +- 8.43 PD in the
younger group and 26.41 +- 8.05 PD in the older group which was
significantly larger in the younger group.
36 (61.0%) of 59 patients in younger group achieved surgical success,
1 (1.70%) had overcorrection and 22 (37.3%) had recurrence. In older
group, 177 (62.8%) of 282 patients were successfully aligned, 105
(37.2%) had recurrence. Surgical success rate was not significantly
different between two groups. (p=0.883, Chi-square test)
Success rate was significantly higher when the primary horizontal
deviation is smaller than 35 PD in the younger group (p=0.036,
Chi-square test) and initial esotropia was more prominent at 1 week
after surgery. (p=0.034, Mann-whitney U test) Success rate was not
significantly different whether deviation is below or above 35 PD in
the older group.
Conclusions: Comparable surgical outcome was achieved in patients
with intermittent exotropia between the younger and older group.
Surgical outcome is likely less favorable when horizontal deviation is
larger than 35PD in patients under 4 years old.
Commercial Relationships: Hye Shin Jeon, None; Jae Ho Jung,
None; Hee-Young Choi, None
Program Number: 5225 Poster Board Number: D0230
Presentation Time: 3:45 PM–5:30 PM
Surgical strabismus in Down syndrome patients
Jeffrey Hollander, Luai Eldweik, Danielle Ledoux. Ophthalmology,
Boston Children’s Hospital, Boston, MA.
Purpose: There is an increased incidence of acquired strabismus
in the Down syndrome population, more commonly resulting in
esotropia than other deviations. We performed a retrospective chart
review of the Down syndrome population with esotropia who had
strabismus surgery to better understand the types of esotropia seen
and the surgical outcomes.
Methods: We performed a seven year (2007–2014) retrospective
chart review of all patients with a diagnosis of Down syndrome
who had surgery for strabismus at a single, tertiary care center. Data
including indications for surgery, preoperative and postoperative
sensorimotor exam, presence of anomalous head posture, and type of
surgery were recorded. Postoperative exam was at least one month
after surgery. Surgical success was defined using three criteria: i)
orthotropia to an esotropia of less than, or equal to 8 prism diopters in
primary position, ii) improvement of anomalous head posture, and iii)
no further indication for surgery.
Results: 16 patients were identified who had Down syndrome
and were surgically treated for esotropia. Of these 1 was excluded
due to follow-up of only two weeks. Preoperative findings of the
remaining 15 patients included 8 (53%) with an A-pattern, 1 (7%)
with a V-pattern, 1 (7%) with a head tilt dependent esotropia, 2 (13%)
who had no assessment of pattern, and 3 (20%) with no pattern of
esotropia. Anomalous head postures were appreciated in 5 (33%)
patients preoperatively, resolved in 4 patients postoperatively, and
persisted in 1. In addition, 2 other patients had anomalous head
postures not appreciated preoperatively. Of the 8 patients with an
A-pattern esotropia, 4 were treated with only a bilateral medial rectus
recession, 3 (75%) of who required a second surgery. Ultimately, 7 of
the 8 patients achieved successful surgical outcomes. Overall surgical
success in this study was 87% (13/15). 2 patients were deemed
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
surgical failures due to persistence of anomalous head posture and
esotropia.
Conclusions: Surgical success was achieved in 87% of patients with
Down syndrome and esotropia. We identified an increased incidence
of A-pattern strabismus in the Down syndrome population, a finding
not previously noted. All 3 patients who required reoperation had
A-patterns that were not addressed at the time of surgery. Ultimately,
88% of patients with A-pattern strabismus achieved successful
surgical outcomes. Recognition of patterns preoperatively may help
guide the surgical plan.
Commercial Relationships: Jeffrey Hollander, None; Luai
Eldweik, None; Danielle Ledoux, None
Program Number: 5226 Poster Board Number: D0231
Presentation Time: 3:45 PM–5:30 PM
Minimally invasive adjustable suture marginal tenotomy and
plication for correction of incomitant vertical strabismus and
torsion
Melinda Chang, Stacy Pineles, Federico Velez. Ophthalmology, Jules
Stein Eye Institute, Los Angeles, CA.
Purpose: To evaluate the effectiveness of minimally invasive
adjustable suture marginal tenotomy and plication of vertical rectus
muscles in correcting incomitant vertical strabismus and torsion.
Methods: Retrospective review of all patients who underwent
marginal tenotomy or marginal plication of a vertical rectus muscle
for correction of incomitant vertical strabismus or torsion by a single
surgeon at a single Eye Institute from July 2013 to September 2014.
Patients were excluded if they did not complete at least 6 weeks of
follow-up.
Results: A total of 10 patients were identified. Two patients
underwent monitored anesthesia care, and eight patients had general
anesthesia. Marginal plications were performed on five patients,
two of whom had incomitant vertical strabismus, one of whom had
cyclotorsion without incomitant vertical strabismus, and two of
whom had both. Marginal tenotomies were performed on five patients
to correct both incomitant vertical strabismus and cyclotorsion.
Two patients were adjusted postoperatively. Marginal plications
corrected a mean of 10 prism diopters (range 4 to 14 prism diopters)
of incomitant deviation, from a mean of 10.75 prism diopters (range
4 to 14 prism diopters) preoperatively. Marginal plications corrected
a mean of 2 degrees of cyclotorsion (range 4 degrees increase in
torsion to 8 degrees decrease in torsion), from a mean preoperative
torsion of 8 degrees (range 11 degrees incyclotorsion to 8 degrees
excyclotorsion). Marginal tenotomies corrected a mean of 4.7 prism
diopters (range 2 to 9 prism diopters) of vertical incomitance, from a
mean of 5 prism diopters (range 2 to 9 prism diopters) preoperatively.
Marginal tenotomies corrected a mean of 3.7 degrees of cyclotorsion
(range 0.5 degrees increase in torsion to 9 degrees decrease in
torsion) from a mean preoperative torsion of 7.3 degrees (range 5
to 10 degrees excyclotorsion). Nine of 10 patients had resolution of
vertical and torsional diplopia postoperatively.
Conclusions: Minimally invasive marginal tenotomy and marginal
plication surgeries are effective in reducing or eliminating incomitant
vertical strabismus. Their effect on torsion is more variable. They are
advantageous compared to surgery on oblique muscles, especially
the inferior oblique, because they can be performed under monitored
anesthesia care with intraoperative and/or postoperative adjustment.
Commercial Relationships: Melinda Chang, None; Stacy Pineles,
None; Federico Velez, None
Program Number: 5227 Poster Board Number: D0232
Presentation Time: 3:45 PM–5:30 PM
Comparing refractive error distribution in children with
Intermittent Exotropia from the Chinese and American NonChinese ethnicity
Mellisa Hege1, Jason CS Yam2, Simon Ko3, Gabriela Chong3,
Jeremy Kwok3, Laila Mossa-Basha4, Shanshan Li5, Jingyun
Wang1. 1Opthalmalogy, Glick Eye Institute-IUSM, Indianapolis,
IN; 2Department of Ophthalmology and Visual Sciences, Chinese
University of Hong Kong, Hong Kong, China; 3Department of
Ophthalmology, Tung Wah Eastern Hospital, Hong Kong, China;
4
Marian University College of Osteopathic Medicine, Indianapolis,
IN; 5School of Public Health, Indiana University Purdue University at
Indianapolis, Indianapolis, IN.
Purpose: Children with Intermittent Exotropia (IXT) in the West
are often emmetropic or low hyperopic (Abrahamsson et al, 1992).
However, the prevalence of myopia has been reported to be higher
in Chinese ethnicity (Pan et al, 2012). It is possible that Chinese
children with IXT are more myopic than children with IXT in
the western countries. This study compared the refractive error
distribution at the age of detection in children with IXT in Hong
Kong to children with IXT in Indiana, USA.
Methods: Retrospective cohort study of children with IXT from
Hong-Kong (Chinese ethnicity) and Indiana (American NonChinese ethnicity: 85% Caucasian and 15% of other races, excluding
Chinese). Eligibility criteria included: 3 to 15 years old, diagnosed
with IXT, no prior surgery, no Down syndrome or other systematic
or genetic conditions, and birth age >36 weeks. Cycloplegic
refractive errors at the age of detection culled from medical records
were converted to a spherical equivalent (SEQ) in diopters (D).
Astigmatism was estimated by the magnitude of cylinder (CYL).
Both SEQ and CYLwere analyzed for two age subgroups: a 3- to
7-year-old subgroup and an 8- to 15-year-old subgroup. To compare
the SEQ difference between the two groups, an independent t-test
was used. Due to the general similarity of refractive error in both
eyes in children with IXT, only the results from the right eye were
reported.
Results: The study included 156 patients. On average, SEQ is more
myopic in the Chinese group than in the American non-Chinese
group. The SEQ of Chinese children in two age subgroups were
all significantly more myopic than that of American non-Chinese
Children (p<0.05, see Table 1). In both Chinese and Non-Chinese
groups, the mean SEQ was significantly more myopic in the 8-15
year-old subgroup than in the 3-7 year-old subgroup (P<0.01, Table
1). However, there was no significant difference on the CYL between
groups (p=0.6).
Conclusions: Compared to American Non-Chinese children with
IXT, Chinese children with IXT are more myopic. Also, older
children tend to be more myopic. Such distribution may be associated
with the high prevalence of myopia in Chinese ethnicity.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Commercial Relationships: Jan Roelof Polling, None; Willem
Tideman, None; Vincent Jaddoe, None; Albert Hofman, None;
Caroline C. Klaver, None
Commercial Relationships: Mellisa Hege, None; Jason CS Yam,
None; Simon Ko, None; Gabriela Chong, None; Jeremy Kwok,
None; Laila Mossa-Basha, None; Shanshan Li, None; Jingyun
Wang, None
Program Number: 5228 Poster Board Number: D0233
Presentation Time: 3:45 PM–5:30 PM
Refractive error determines type of strabismus: The Generation
R study
Jan Roelof Polling3, 2, Willem Tideman3, Vincent Jaddoe1, Albert
Hofman1, Caroline C. Klaver1. 1Epidemiology, Erasmus MC,
Rotterdam, Netherlands; 2Orthoptics & Optometry, University
of Applied Sciences, Faculty of Health, Utrecht, Netherlands;
3
Ophthalmology, Erasmus MC, Rotterdam, Netherlands.
Purpose: Previous studies suggest that the prevalence of strabismus
subtypes is related to ethnicity, with exotropia being more frequent
in Asian populations and esotropia in Caucasian populations. This
predilection may be determined by refractive error. We investigated
the relationship between strabismus subtype and refractive error in a
large population-based cohort of young children.
Methods: The Generation R Study is a multi-ethnic population-based
birth-cohort study in Rotterdam, the Netherlands, which includes
6690 children. LogMAR visual acuity (LEA charts) was determined
at age 6, and those with LogMAR acuity > 0.1 or those receiving
ophthalmic care were evaluated for ocular alignment and cycloplegic
refraction. Strabismus subtype was determined by the treating
orthoptist according to a national classification system.
Results: Mean age of children was 6.2 (SD ±0.5) years., N=110
(1.6%)children were identified with a manifest strabismus. Of
these convergent strabismus was most common (n = 74, 1.1%),
with accommodative esotropia (n = 55, 0.82%) as nost common
subtype, followed by constant esotropia (n = 15, 0.2%) and infantile
esotropia (n = 4, 0.06%). Exotropia was detected in n=25 (0.4%)
children; n=10 (0.1%) children had special forms of strabismus
such as congenital trochlear palsy, Duane, congenital fibrosis and
acquired palsy. Mean spherical equivalent was +4.67D (SD ±1.94)
in accommodative esotropia and +0.04D (SD 2.17; P<0.01) in
exotropia.
Conclusions: Type of strabismus appears to be associated to
refractive error; exotropic children are more myopic, whereas
esotropic children are more hyperopic. The increasing prevalence of
myopia worldwide may determine the relative increase of exotropia
and may be the cause of the ethnic variation in strabismus subtypes.
Program Number: 5229 Poster Board Number: D0234
Presentation Time: 3:45 PM–5:30 PM
Acquired Brown’s Syndrome in children:
MRI abnormalities of the superior oblique tendon-trochlea
complex
Christina Gerth-Kahlert1, Veit Sturm2, Werner Wichmann3.
1
Ophthalmology, University Hospital Zurich, Zurich, Switzerland;
2
Ophthalmology, Cantonal Hospital St. Gallen, St. Gallen,
Switzerland; 3Neuroradiology, University Hospital, Zurich,
Switzerland.
Purpose: To characterize and demonstrate structural abnormalities in
the rare instance of acquired Brown’s syndrome in children.
Methods: Retrospective chart review of pediatric patients with
the diagnosis of non- congenital Brown’s syndrome. Blinded reevaluation of available MR imaging was performed.
Results: Three patients (2 female, 1 male) with an age at onset of
first symptoms of 6.2, 8.2 and 8.5 years were identified. Signs and
symptoms at onset were diplopia, abnormal head posture (AHP)
and strabismus. 2/3 children had a documented normal orthoptic
examination prior to the acute onset of vertical strabismus. All
children lacked other neurological signs. MRI performed between 10
days and 8 weeks after first diagnosis showed contrast enhancement
of the superior oblique tendon in 2/3 and thickening in the area
of the trochlea- tendon complex in 2/3 cases. Clinical follow up
demonstrated improved motility with consecutive reduction of
diplopia and extent of AHP in 2/3 cases after 0.4 to 1.4 years.
Conclusions: Acquired Brown’s syndrome might be caused by
a localized inflammation of the superior oblique tendon/ trochlea
complex. Despite the good clinical outcome, MR imaging in patients
with an acute onset is recommended to exclude other etiologies.
Commercial Relationships: Christina Gerth-Kahlert, None; Veit
Sturm, None; Werner Wichmann, None
Program Number: 5230 Poster Board Number: D0235
Presentation Time: 3:45 PM–5:30 PM
Clinical Characteristics of Exodeviated Patients from
Accomodative Esotropia and Hyperopia
Sang H. Rah, Soo Han Kim. Ophthalmology, Wonju Severance
Christian Hospital, Wonju, Korea (the Republic of).
Purpose: To evaluated the characteristics of exodeviated patients
form accomodative esotropia and hyperopia.
Methods: Chart review of patients from Jan 1st 1997 to DEC 31st
2013. Patients developed exotropia from accommodative esotropia
and hyperopia. Patient whom received surgery for strabismus were
excluded.
Results: 13 patient was recognized. Initially patient was referred at
mean 4.1years old. Cycloplegic refraction mean +5.58 Diopter (D)
at initial. 10 Patients(76.9%) had accommodative esotropia with
mean 24.75 Prism Diopter (PD) at near gaze. 7 patient (53.8%) had
bilateral amblyopia with average visual acuity of 0.3 and spherical
equivalent of +5.74D. 6 patients (46.15%) had monocular amblyopia
with visual acuity of 0.25 at amblyopic eye and 0.55 at dominant eye.
Spherical equivalent of amblyopic eye was +5.93D and +4.79D in
dominant eye. Exodeviation was first appeared at average 9.2 years of
age. Spherical equivalent was +4.50D in bilateral amblyopic patients.
In patients with monocular amblyopia spherical equivalent was
+3.60D in amblyopic eye and +2.17D in dominant eye. Exodeviation
was average 13.1PD but ranged from small exotropia to 16 PD
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
exotropia. Patient with residual hyperopia(83.8%), exotropia was
successfully decreased with spectacle correction.
Conclusions: All patients who developed exotropia form
accomodative esotropia and hyperopia had bilateral or unilateral
amblyopia. Observation is needed in case of accommodative
esotropia and hyperopia, since exodeviation could develop. Exotropia
was successfully managed with spectacle correction. Further study is
needed for possible surgical intervention.
Commercial Relationships: Sang H. Rah, None; Soo Han Kim,
None
511 Optic neuritis / Optic nerve
Thursday, May 07, 2015 8:30 AM–10:15 AM
Exhibit Hall Poster Session
Program #/Board # Range: 5528–5560/B0099–B0131
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Contributing Section(s): Biochemistry/Molecular Biology, Clinical/
Epidemiologic Research, Visual Neuroscience
Program Number: 5528 Poster Board Number: B0099
Presentation Time: 8:30 AM–10:15 AM
Neuroprotective Effects of Amnion-derived Cellular Cytokine
Solution (ACCS) in Experimental Optic Neuritis
Reas Sulaimankutty1, Kimberly Dine1, Helayna Brown1, Larry
R. Brown2, Kenneth S. Shindler1. 1Ophthalmology, Univ of
Pennsylvania, Scheie Eye Inst, Philadelphia, PA; 2Stemnion Inc,
Pittsburgh, PA.
Purpose: Optic neuritis is a demyelinating inflammation of the optic
nerve that often occurs in multiple sclerosis (MS) patients. Loss of
retinal ganglion cells (RGCs) and their axons also occurs in optic
neuritis, and correlates with permanent vision loss. ACCS is a novel
biologic mixture of growth factors and cytokines secreted from
Amnion-derived Multipotent Progenitor (AMP) cells, that exhibits
anti-inflammatory and neuroprotective properties in a variety of
disease models. The ability of ACCS to suppress optic neuritis in the
experimental autoimmune encephalomyelitis (EAE) model of MS
was examined.
Methods: EAE was induced in C57/BL6 mice by immunization with
myelin oligodendroglial glycoprotein peptide. Mice were treated
daily with one drop (6 uL) of ACCS intranasally beginning before
or after onset of optic neuritis. Visual function was assessed by
optokinetic responses (OKR) at baseline, then weekly until sacrifice
6 weeks post-immunization. Retinas and optic nerves were isolated.
RGCs were immunolabeled with Brn3a antibodies to quantify RGC
survival. Inflammation was assessed by H&E and Iba1 (macrophage/
microglia marker) staining, demyelination by luxol fast blue staining,
and axonal loss by neurofilament staining of optic nerve sections.
Results: Progressive decreases in OKR occurred in vehicle-treated
EAE mice, along with significant RGC loss, consistent with prior
studies showing onset of optic neuritis occurring 12-15 days after
EAE induction. Daily intranasal ACCS treatment beginning on
day 0 (day of immunization), 15, 22, or 30, significantly reduced
the level of vision loss, and treatment from day 0 or day 15
significantly attenuated RGC loss. ACCS also decreased the degree of
demyelination and axonal loss, but had limited effects on the level of
inflammation in the optic nerve.
Conclusions: ACCS treatment attenuates RGC loss, preserves
OKR responses, and reduces demyelination and axonal loss during
experimental optic neuritis in EAE mice. ACCS exerts effects with
treatment initiated before and after onset of optic neuritis, suggesting
it may be useful as a preventative or abortive therapy. Results suggest
ACCS is a potential treatment for optic neuritis that warrants further
study. Furthermore, potent effects seen after intranasal administration
suggest this may be a novel drug delivery method for optic neuritis.
Commercial Relationships: Reas Sulaimankutty, None; Kimberly
Dine, None; Helayna Brown, None; Larry R. Brown, Stemnion Inc
(I); Kenneth S. Shindler, Stemnion Inc (F)
Support: NIH Grant EY019014
Program Number: 5529 Poster Board Number: B0100
Presentation Time: 8:30 AM–10:15 AM
Experimental optic neuritis induced by the microinjection of
lipopolysaccharide into the optic nerve
Marcos Luis Aranda, Damian Dorfman, Pablo Sande, Ruth E.
Rosenstein. Human Biochemistry, University of Buenos Aires /Sch of
Medicine, Buenos Aires, Argentina.
Purpose: Optic neuritis (ON) is a condition involving primary
inflammation, demyelination, and axonal injury in the optic
nerve which leads to retinal ganglion cell (RGC) loss, and visual
dysfunction. We investigated the ability of a single microinjection
of bacterial lipopolysaccharide (LPS) directly into the optic nerve to
induce functional and structural alterations compatible with ON. For
this purpose, optic nerves from male Wistar rats remained intact or
were injected with vehicle or LPS.
Methods: The effect of LPS was evaluated at several time points
post-injection in terms of: i) visual pathway and retinal function
(visual evoked potentials (VEPs) and electroretinograms, (ERGs),
respectively), ii) anterograde transport from the retina to its
projection areas, iii) consensual pupil light reflex (PLR), iv) optic
nerve histology, v) microglia/macrophage reactivity (by Iba1- and ED1-immunostaining), vi) astrocyte reactivity (by glial
fibrillary acid protein-immunostaining), vii) axon number (by
toluidine blue staining), vii) demyelination (by myelin basic protein
immunoreactivity and luxol fast blue staining), viii) optic nerve
ultrastructure, and ix) RGC number (by Brn3a immunoreactivity).
Results: LPS induced a significant and persistent decrease in VEP
amplitude and PLR,without changes in the ERG. In addition, LPS
induced a deficit in anterograde transport, and an early inflammatory
response consisting in an increased cellularity, and Iba-1 and ED1immunoreactivity in the optic nerve, which were followed by changes
in axonal density, astrocytosis, demyelination, and axon and RGC
loss.
Conclusions: These results suggest that the microinjection of LPS
into the optic nerve may serve as a new experimental model of
primary ON.
Commercial Relationships: Marcos Luis Aranda, None; Damian
Dorfman, None; Pablo Sande, None; Ruth E. Rosenstein, None
Support: CONICET-PIP0446, ANPCyT-PICT0610, FUNDACION
FLORENCIO FIORINI, UBA
Program Number: 5530 Poster Board Number: B0101
Presentation Time: 8:30 AM–10:15 AM
Impaired axonal transport in a rodent model of optic neuritis due
to NMO spectrum disorder
Yoshiko Matsumoto1, Akiyasu Kanamori1, Sho Nobuyoshi1, Ichiro
Nakashima2, Makoto Nakamura1. 1Department of Ophthalmology,
Kobe University Graduate School of Medicine, Kobe, Japan;
2
Department of Neurology, Tohoku University Graduate School of
Medicine, Sendai, Japan.
Purpose: We previously reported that exposure of serum from
patients with seropositive neuromyelitis optica spectrum disorders
(NMOSDs) led to astrocytic damage at 7 days. However, axonal
loss was not detected at that time (Matsumoto Y, et al. Exp. Eye Res.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
2014). The purpose of this study was to evaluate whether axonal
transport is impaired in a rodent model of optic neuritis in NMOSDs.
Methods: We collected serum from patients with idiopathic or
NMO-optic neuritis or from normal subjects. Using male SpragueDawley rats (200-300g), we exposed the rat optic nerve to the
collected serum as previously reported. The treated rats were divided
into those exposed to aquaporin 4 (AQP4) autoantibody-positive
serum (AQP4+) or those exposed to AQP4 antibody-negative serum
(AQP4-). Seven days (7D) and 14 days (14D) after treatment, rats
were sacrificed and the optic nerves were excised. Cryosections
of the optic nerves were subjected to immunohistochemistry
against neurofilament (NF) and kinesin1-kif5b (Kif5b). Real-time
polymerase chain reaction (RT-PCR) analyses were also conducted to
evaluate Kif5b gene expressions.
Results: Linear Ki5b immunoreactivity (IR) was co-localized with
NF expression in the optic nerves. Aggregated IR of Kif5b was
scattered in the optic nerves of the AQP4+ group at 7D. The number
of the aggregated Kif5b IR in the AQP4+ group was statistically
increased than that in the AQP4- group (n=8 each, unpaired t-test;
p=0.02). The gene expression of Kif5b was significantly decreased in
the AQP4+ group at 14D compared with controls (n=6 each, unpaired
t-test; p=0.02), but not in the AQP4- group.
Conclusions: Given that kinesin1-Ki5b plays a critical role in
the anterograde axonal transport, the present study suggested that
axonal transport is impaired in the optic nerves of rodent models of
NMOSDs before detectable axonal loss.
Commercial Relationships: Yoshiko Matsumoto, None; Akiyasu
Kanamori, None; Sho Nobuyoshi, None; Ichiro Nakashima, None;
Makoto Nakamura, None
Support: JSPS KAKENHI, The Uehara Memorial Foundation
Program Number: 5531 Poster Board Number: B0102
Presentation Time: 8:30 AM–10:15 AM
Phosphatase and Tensin Homolog (PTEN) Knockout in Retinal
Ganglion Cells (RGCs) Rescues Optic Neuritis in Experimental
Autoimmune Encephalomyelitis (EAE) Mice
Venu Talla1, Vince Chiodo2, Vittorio Porciatti1, Sanford L. Boye2,
William W. Hauswirth2, John Guy1. 1Ophthalmology, Bascom Palmer
Eye Institute, Miami, FL; 2Department of Ophthalmology, University
of Florida, Gainesville, FL.
Purpose: To rescue visual loss and optic neuropathy in EAE mouse
model using ssAAV2Cre-GFP mediated knockout (KO) of floxed
PTEN (PTEN fl/fl), a negative regulator of mTOR (mammalian target
of rapamycin) pathway involved in optic nerve axonal regeneration
in RGCs.
Methods: EAE was induced in floxed-PTEN mice (n=11) and
littermates (n=8) by subdermal injection of 0.1 ml homologous spinal
cord emulsion in complete Freunds adjuvant in the nuchal area. EAE
sensitized floxed-PTEN mice received an intravitreal injection of
ssAAV-Cre-GFP into both eyes whereas EAE littermates received
scAAV-mCherry as an injection control. Unsensitized littermates
with or without scAAV-mCherry injections acted as additional
controls (n=16). Visual function was assessed by recording pattern
electroretinograms (PERG). Spectral domain OCT evaluated the
thickness of the inner plexiform layer to the nerve fiber layer at 1, 4
and 9 months post injection (MPI). Expression of the Cre-GFP in the
RGCs and ONs were evaluated in live mice by confocal scanning
laser ophthalmoscope (CSLO) imaging at 5 and 9 MPI. Retina and
ON tissues were dissected and Tuj1 labeled RGCs and ON axons
were evaluated by immunofluorescence.
Results: Expression: CSLO imaging at 5 and 9MPI in live EAE
floxed-PTEN mice revealed expression of Cre-GFP in RGC layer.
Rescue: PERG analysis at 1M, 4M and 9MPI showed a 25%, 37%
and 41% reduction in amplitude of EAE-mCherry mice compared
to mCherry/control mice (p<0.005). The PERG latencies were also
delayed by 7%, 17% and 27% in EAE-mCherry at 1M, 4M (p<0.05)
and 9MPI (p<0.05). Interestingly, knockout of PTEN in EAE mice
RGCs by AAV2-Cre-GFP injection rescued the amplitudes by 51,
54 and 77% (p<0.005) at 1, 4 & 9MPI. However, the latencies were
not significantly rescued compared to EAE-mcherry. OCT images
of the EAE-mCherry mice showed a significant thinning (p<0.005)
in RNFL/RGC/inner plexiform layers while the OCT images of the
PTEN (KO) EAE mice were 150% (p<0.0001) & 122% (p<0.0001)
thicker compared to control at 5 & 9 MPI. Quantitative analysis of
Tuj1 positive cells revealed 57% rescue of RGCs in PTEN (KO) mice
compared to EAE mice (p<0.05).
Conclusions: PTEN is involved in intrinsic axonal growth arrest and
knocking out the PTEN in RGCs is a strategy that may be useful for
treating the 8% of optic neuritis patients experiencing permanent loss
of vision.
Commercial Relationships: Venu Talla, None; Vince Chiodo,
None; Vittorio Porciatti, None; Sanford L. Boye, None; William
W. Hauswirth, AGTC (F); John Guy, None
Support: R01EY07892, EY017141, EY012355, EY019077, NIH
center grant P30-EY014801, unrestricted grant to Bascom Palmer
Eye Institute from Research to Prevent Blindness, Inc.
Program Number: 5532 Poster Board Number: B0103
Presentation Time: 8:30 AM–10:15 AM
Changes of CXCL12, CXCL14 and PDGF levels in the brain
of patients with idiopathic demyelinating optic neuritis and
neuromyelitis optica
Tingjun Chen. neuro ophthalmology, Beijing, China.
Purpose: The CXC chemokines (CXC-motif ligand 12 and CXCmotif ligand 14) and platelet-derived growth factor are suggested
to modulate remyelination in the course of many demyelinating
diseases. The present study compared the difference in the brain
levels of these chemokines between patients with idiopathic
demyelinating optic neuritis (IDON) and neuromyelitis optica
(NMO) by measuring concentrations of these chemokines in the
cerebrospinal fluid using an enzyme linked immunosorbent assay.
Methods:
In this study, PDGF, CXCL12 and CXCL14 levels in the CSF of
IDON and NMO patients were measured by ELISA and compared,
and non-inflammatory neural disease (NIND) patients were used as
negative control as reported by others .
Results:
Our data indicate that the prognosis of neuritis depends on the
remyelinating process that is impaired due to decreased chemokines.
The much lower levels of chemokines would specifically indicate the
severe neuritis, such as NMO.
Conclusions:
In conclusion, the present study strongly suggests that chemokines,
PDGF, CXCL12 and CXCL14, may alone and/or together associate
with these two types of ON. The former two would serve to
stimulate the maturation of OPCs, and the last one is a possible OPC
maturation inhibitor.
Commercial Relationships: Tingjun Chen, None
Support: Chinese Postdoctoral Science Foundation
(No.2013M542249)
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 5533 Poster Board Number: B0104
Presentation Time: 8:30 AM–10:15 AM
Color cone contrast testing adds predictive value of visual
function in combination with low-contrast testing in multiple
sclerosis
Hao Yiu, Samuel Arnow, Jeffrey Gelfand, Christopher Songster,
Denise Bolivar, Ari Green. Neurology, University of California, San
Francisco, San Francisco, CA.
Purpose: Low contrast visual function has been validated as
an important clinical outcome measure in both observational
and therapeutic investigational studies in multiple sclerosis.
Computerized tests of visual performance provide convenient
measures of visual function in the clinic. Subjects with multiple
sclerosis frequently have structural injury to the retina that can
be assessed via spectral-domain optical coherence tomography.
Recent advances in software algorithms allow segmentation and
quantification of individual retinal layers.
Methods: We performed Rabin cone contrast testing (CCT),
computerized low contrast threshold testing (LCT), and Heidelberg
Spectralis spectral-domain optical coherence tomography (SD-OCT)
in 52 people with multiple sclerosis (MS) (102 eyes, 71% female, 18
with a history of a prior optic neuritis). Linear mixed-models were
used to analyze the association between cone-contrast and lowcontrast visual function and retinal layer thickness, adjusting for age,
sex, history of optic neuritis, and accounting for intra-subject intereye correlations.
Results: Red, Blue, and Green CCT scores were positively correlated
with macular ganglion cell / inner plexiform layer (GCIPL) thickness
(p<0.001), but were not significantly associated with the thickness of
other retinal layers. Linear mixed-effect regression models predicting
GCIPL thickness showed significant improvement with the addition
of LCT scores (change in deviance of 79.0 and 81.0 in models with
and without CCT, respectively). The addition of CCT had a lower
magnitude but significant effect on model deviance even when low
contrast vision was included as a predictor in the model (change
in deviance of 33.6 and 27.4 on models with and without LCT,
respectively).
Conclusions: Color cone contrast testing is correlated with GCLIP
thickness in MS and provides added predictive value of visual
pathway injury in combination with low-contrast testing in MS
patients.
Commercial Relationships: Hao Yiu, None; Samuel Arnow, None;
Jeffrey Gelfand, Journal Watch Neurology (Massachusetts Medical
Society) (R), Medical Legal Consulting (C); Christopher Songster,
None; Denise Bolivar, None; Ari Green, Accorda (C), Biogen (C),
Biogen/Idec/Applied Clinical Intelligence (R), Novartis (C), Prana
Bioscience (C), Roche (C)
Program Number: 5534 Poster Board Number: B0105
Presentation Time: 8:30 AM–10:15 AM
Visual outcome predictors in acute optic neuritis
Sangah Kim, Samin Hong, Chan Yun Kim, Gong Je Seong.
Ophthalmology, Yonsei University College of Medicine, Seoul,
Korea (the Republic of).
Purpose: To find the visual outcome predictors in patients who
received intravenous steroid pulse therapy (ISPT) due to acute optic
neuritis (AON).
Methods: A retrospective, observational, clinical study. A total
of 33 AON patients received ISPT (methylprednisolone, 250 mg,
four times a day, 3 days) and had follow-up checkups for at least 3
months after the therapy were included in this study. Patients were
divided into two groups, those who finally recovered their vision over
LogMAR 0.3 (Group 1, n=25) vs. those who didn’t (Group 2, n=8).
We evaluated the demographics and clinical characteristics and tried
to determine which factors had affected the visual outcome.
Results: The presence of a relative afferent pupillary defect (RAPD)
and a pattern of visual field (VF) defect at presentation, and the
degree of visual loss at the 3 month and 1 year after treatment were
associated to the final visual outcome. While, age, gender, bilaterality,
moving pain, headaches, and the degree of vision and color sense
loss were not related to the final visual outcome. The presence of disc
swelling and retinal nerve fiber layer (RNFL) defect, the abnormal
responses on visual evoked potential (VEP), the abnormal level of
erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)
were also not associated with the final visual outcome.
Conclusions: At presentation, the RAPD and VF defect excluding
visual loss were associated with the final visual outcome in AON
patients who had received ISPT. Regarding vision, the visual acuity
at 3 months and 1 year after treatment were associated with the final
visual outcome.
Commercial Relationships: Sangah Kim, None; Samin Hong,
None; Chan Yun Kim, None; Gong Je Seong, None
Program Number: 5535 Poster Board Number: B0106
Presentation Time: 8:30 AM–10:15 AM
Retinal Sensitivity Reduced in Patients with Neuromyelitis
Optica Spectrum Disorder with no History of Optic Neuritis
Ryutaro Akiba1, Hirotaka Yokouchi1, Takayuki Baba1, Toshiyuki
Oshitari1, Setsu Sawai2, Masahiro Mori2, Satoshi Kuwabara2,
Shuichi Yamamoto1. 1Ophthalmology and Visual Science, Chiba
University Graduate School of Medicine, Chiba, Japan; 2Department
of Neurology, Chiba University Graduate School of Medicine, Chiba,
Japan.
Purpose: Neuromyelitis optica spectrum disorder (NMOSD) is
an inflammatory autoimmune disease that can cause severe optic
neuritis (ON) and myelitis. The results of previous studies have
suggested that early structural changes of retina were present in
patients with multiple sclerosis (MS) who have no history of ON.
However, there has been very few reports of functional or structural
changes in patients with NMOSD who have no history of ON. The
purpose of this study was to determine the retinal sensitivity by
microperimetry and retinal structure by spectral-domain optical
coherence tomography (SD-OCT) in patients with NMOSD who
have no history of ON. In addition, we compared the early functional
and structural changes of the retina of patients with NMOSD to that
of healthy controls.
Methods: Twelve eyes of 6 patients with NMOSD who had no
history of ON were studied, the NMOSD group. We determined the
retinal sensitivity of the central 100 (37 points) and central 20 (13
points) by macular integrity assessment (MAIA). We also measured
the best-corrected visual acuity (BCVA) expressed in logarithm of
minimum angle of resolution (logMAR) units and retinal structure
by SD-OCT. We quantified the mean thickness of the retinal nerve
fiber layer (RNFL) and ganglion cell layer (GCL) from the OCT
images. Twenty-five eyes of 13 volunteers who had no high myopia,
glaucoma, or other macular disorders were included in the HC
groups.
Results: There was no significant difference in the BCVA (P=0.168),
age (P=0.321), and refractive error (P=0.549) between the NMOSD
and HC groups. The retinal sensitivity of the central 100 (NMOSD,
27.65±1.75 dB; HC, 29.12±0.85 dB) and 2 degrees (NMOSD,
27.68±1.96 dB; HC,29.41±1.12 dB) were significantly lower in the
NMOSD group (P=0.015 and P=0.015 respectively, Mann-Whitney
U-test). The RNFL thickness (NMOSD, 109.5±14.6 μm; HC,
107.2±7.4 μm), and GCL thickness(NMOSD, 94.7±12.0 μm; HC,
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
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ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
97.5±5.2 μm) were not significantly different between the two groups
(P=0.527, P=0.557 respectively, Mann-Whitney U-test).
Conclusions: These results indicate that the retinal sensitivity
is impaired even before the development of ON in NMOSD
patients, and also that the functional impairments precede the
structural impairments. Although further investigations are needed,
microperimetry appears useful to determine subclinical change of
retina in eyes with NMOSD
Commercial Relationships: Ryutaro Akiba, None; Hirotaka
Yokouchi, None; Takayuki Baba, None; Toshiyuki Oshitari, None;
Setsu Sawai, None; Masahiro Mori, None; Satoshi Kuwabara,
None; Shuichi Yamamoto, None
Program Number: 5536 Poster Board Number: B0107
Presentation Time: 8:30 AM–10:15 AM
Evaluation of ganglion cell complex after optic neuritis by OCT
Annalisa Costa1, Christian Cordano2, Antonella Panizzi1, Laura
Landi1, Federico Bisio1, Alessandro Bagnis1, Carlo E. Traverso1,
antonio uccelli2, Antonio Ferreras3, Michele M. Iester1. 1DINOGMI,
University of Genoa Eye Clinic, Genova, Italy; 2DiNOGMI,
University of Genoa, Clinica Neurologica, Genova, Italy; 3University
eye clinic, Zaragoza, Spain.
Purpose: To compare the macular assessment and RNFL thickness
by using two different OCTs: a time domain (TD) and a spectral
domain (SD) OCT, in patients with unilateral optic neuritis.
Methods: This is a retrospective study. 34 multiple sclerosis (MS)
subjects with a single unilateral optic neuritis (ON) were included in
the study. An ophthalmological examination, TD OCT and SD OCT
were performed. The following parameters were selected: Superior
max, Inferior max, Inferior average thickness, Superior average
thickness, Average thickness and Foveal thickness from TD OCT
and Average ganglion cell complex, superior ganglion cell complex,
inferior ganglion cell complex, focal loss ganglion cell complex,
global loss ganglion cell complex, average full retina, superior full
retina, inferior full retina, focal loss full retina, global loss full retina,
average outer retina, superior outer retina, inferior outer retina,focal
loss outer retina, global loss outer retina from SD OCT. Student’s
t-test was used to compare the two sets of data when the distribution
of the data was normal. Mann–Whitney test coefficient was utilized
to compare the two sets of data when they did not follow a normal
distribution. The statistical power of the study ranged between
76.2 and 94.2% with an alpha of 0.05 and a beta of 0.5. Bonferroni
correction was applied to Student’s t-test because otherwise we would
have a significant chance of 40.1% of our finding.
Results: In the affected eye group a reduction of the average
thickness of retinal nerve fibre layer (RNFL) was found using
TD OCT and the reduction was of 22.78% and the difference was
statistically significant (P<0.001) between the two groups in almost
all the investigated retina areas. Similar results were found when
eyes were analysed with SD OCT, also when the ganglion cell layer
(GCC) was considered: a reduction of 18.08% of GCC average
thickness was found. No significant difference was found when the
outer retina was considered.
Conclusions: In MS patients both OCT systems were able to detect
difference between eyes with an outcome of optic neuritis and those
without optic neuritis.
Commercial Relationships: Annalisa Costa, None; Christian
Cordano, None; Antonella Panizzi, None; Laura Landi, None;
Federico Bisio, None; Alessandro Bagnis, None; Carlo E.
Traverso, None; antonio uccelli, None; Antonio Ferreras, None;
Michele M. Iester, None
Program Number: 5537 Poster Board Number: B0108
Presentation Time: 8:30 AM–10:15 AM
Intravitreal injection of erythropoietin in late-stage optic
neuropathy
Bekir Kucuk1, Uğur Acar1, Koray Sevinc2, Seçkin Aykas2, Mesut
Erdurmus1, Gungor Sobaci1. 1Ophthalmology, Hacettepe University,
Ankara, Turkey; 2Ophthalmology, Gulhane Military Medical
Academy, Ankara, Turkey.
Purpose: Recent clinical findings have showed that
erythropoietin(EPO) has both neuroprotective and neuroregenerative
capabilities for axonal degenerative disease of the optic nerve. In this
retrospective interventional study, we evaluated if intravitreal EPO
administration has any neuroregenerative effect in patients with latestage optic neuropathy, or not.
Methods: Twelve eyes of 12 patients with optic atrophy[(defined
as overall thinning(90 mm)in the retinal nerve fiber layer(RNFL)]
from definite demyelinating optic neuritis history were included.
Patients who had both minimum 6-months medical history and light
perception vision in the affected eye, were enrolled into the study.
Using pars plana approach, 2000IU/0.2ml EPO(Eprex4000IU/0.4ml,
Janssen-Cilag AG,Switzerland) was administered intravitreally
with a 30-gauge needle on a tuberculin syringe. Injections were
administered 3-times with 6-weeks intervals. Clinical [Best corrected
visual acuity(BCVA) and opthalmoscopic and laboratory(OCT
measurements, electrodiagnostic tests)] examinations were repeated
at regular intervals, and final visit was performed 3-months after the
third intravitreal EPO injection. The primary outcome parameters,
BCVA and RNFL thickness and secondary outcome parameters,
visual evoked potentials(VEP) and electroretinography(ERG) at
initially and at final visit were analyzed.
Results: No inflammatory, immunological or proliferative response
was detected. The median BCVA of the patients with optic atrophy
was 1.71±1(0.5-3.1)logMAR at initially and 1.69±1(0.5-3.1)
logMAR at final visit. No one obtained minimum 0.2 logMAR BCVA
improvement (success criteria). RNFL value was 49.1±22(22-88)mm
before injections, and 48.6±20(25-81)mm after injections. The mean
amplitude values of combined response in ERG(N35-P50, P50-N95)
were 5.68±2(2.9-10.2)mV, 6.91±3(3.7-14.9)mV before the injections
and 5.45±2.1(2.6-9.6)mV, 6.73±2.5(3.7-12)mV after the injections,
respectively. The mean amplitude and latancy values of response in
VEP 121.25±19.5(90-153) msn and 3.75±2.7(1.4-12)mV before the
injections and 114.8±15(93-134)msn and 3.96±3.1 (0.7-12.4)mV
after the injections, respectively.
Conclusions: Intravitreal EPO injections has no neuroregenerative
effect on the optic nerve when it was administered in the late period
(>6months) of optic neuropathy. Meantime, we did not find any
adverse effects of this administration on visual parameters and retinal
microstructures.
Commercial Relationships: Bekir Kucuk, None; Uğur Acar, None;
Koray Sevinc, None; Seçkin Aykas, None; Mesut Erdurmus,
None; Gungor Sobaci, None
Program Number: 5538 Poster Board Number: B0109
Presentation Time: 8:30 AM–10:15 AM
The design of a randomized clinical trial on the neuroprotective
properties of erythropoietin in optic neuritis: Treatment of Optic
Neuritis with Erythropoietin (TONE)
Wolf Lagrèze1, Ricarda Diem2. 1Ophthalmology, University of
Freiburg, Freiburg im Breisgau, Germany; 2Neurology, University
Heidelberg, Heidelberg, Germany.
Purpose: After successful completion of the VISION PROTECT
pilot trial (NCT00355095) providing the first morphologic
OCT-based evidence for neuroprotection with erythropoietin in
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
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ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
optic neuritis, the German government has recently approved a
subsequent, full-scale, nationwide randomized controlled clinical trial
(NCT01962571), whose design we intend to present here.
Methods: A power analysis based on publications on the natural
course and thinning of the peripapillary retinal nerve fiber layer after
optic neuritis yielded a number of 47 patients in each treatment arm
of a placebo-controlled, randomized, double-blind clinical trial to
demonstrate a treatment effect of 50% reduction of nerve fiber loss
with an α of 0.05 and β of 0.80.
Results: Recruitment of TONE has commenced in December 2014.
Patients are randomized on either i.v. placebo or intravenous 33.000
IU i.v. erythropoietin as an add-on to a 3 day course of i.v. megadose
methylprednisolone. Primary outcome measure is the peripapillary
retinal nerve fiber layer thickness determined with the NSITE 6.0
software of the Spectralis®-OCT. Secondary analyses comprise
retinal layer segmentation. Functional measures are ETDRS-chart
based visual acuity at 2.5% and 100% contrast, contrast sensitivity,
volumetric analysis of the visual field defect determined by the
German Adaptive Threshold Estimation (GATE) algorithm, VEPlatencies and vision-related quality of life. Results are expected after
completion presumably in 2017. A 1.5 year open label follow-up shall
provide further insights of erythropoietin effects with regard to MSprogression.
Conclusions: A positive outcome of the TONE-Trial would not only
provide new treatment options for patients with optic neuritis, but
might promote further clinical research in multiple sclerosis.
Commercial Relationships: Wolf Lagrèze, None; Ricarda Diem,
None
Support: BMBF (German Ministry of Education and Research)
Clinical Trial: NCT01962571
Program Number: 5539 Poster Board Number: B0110
Presentation Time: 8:30 AM–10:15 AM
Early treatment of recombinant human granulocyte colony
stimulating factor (G-CSF) in the rat model of anterior ischemic
optic neuropathy (rAION) reveals a beneficial neuroprotective
effect
Rong-Kung Tsai1, 2, Yao-Tzeng Wen1, Chung Hsing Chang3. 1Institute
of Eye Research, Buddhist Tzu-Chi Medical Center, Hualien,
Taiwan; 2Institute of Medical Sciences, Tzu Chi University, Hualien,
Taiwan; 3Department of Dermatology, Kaohsiung Medical University
Hospital, Kaohsiung, Taiwan.
Purpose: Our previous report demonstrated that immediate
administration of recombinant human granulocyte colony-stimulating
factor (G-CSF) had neuroprotective effects in a rat model of anterior
ischemic optic neuropathy (rAION). This study is aim to investigate
whether delayed treatment of G-CSF is as effective as early treatment
after rAION induction.
Methods: The rAION rats were subcutaneously injected G-CSF
starting at day 0, 7, and 14-post rAION induction for 5 consecutive
days. Survival rate of retinal ganglion cells (RGCs) was determined
by using retrograde labeling of Fluorogold. Apoptosis in RGCs layer
and inflammation at optic nerve (ON) were measured by TUNEL
assay and immunohistochemical (IHC) staining of ED1 respectively.
Visual function was assessed by photoptic flash visual evoked
potentials (FVEP).
Results: G-CSF treatment started at day 0-post rAION induction had
significant better survival rate of RGCs than treatments at day 7 and
14-post infarct both in central and mid-peripheral retinas (p<0.05).
Treatment with G-CSF at day 0-post rAION induction resulted in
significantly lower number of apoptotic cells in RGCs layer of retinas
and significantly lower level of inflammation at ON than treatment at
day 7 and 14-post rAION induction (p<0.05). Rats received G-CSF
treatment at day 0-psot rAION induction preserved better latency and
amplitude of the p1 wave in FVEP than rats treatment with G-CSF at
day 7 and 14-post rAION induction (p<0.05).
Conclusions: Early treatment with G-CSF has significantly better
neuroprotective effects on RGCs and optic nerve than the delayed
treatment starting at 1 or 2 weeks post-infarct.
Commercial Relationships: Rong-Kung Tsai, None; Yao-Tzeng
Wen, None; Chung Hsing Chang, None
Support: 103-2314-B-303 -007 -MY3 from Ministry of Science and
Technology of Taiwan
Program Number: 5540 Poster Board Number: B0111
Presentation Time: 8:30 AM–10:15 AM
The Presence of Calcium Significantly Enhanced Annexin-VLabelling of Degenerating Axons after Experimental Anterior
Ischemic Optic Neuropathy
Gun Ho Lee1, M Ali Shariati1, Ming-Hui Sun1, 2, Yaping J. Liao1.
1
Stanford University, Cupertino, CA; 2Chang Gung Memorial
Hospital - LinKou, LinKou, Taiwan.
Purpose: Annexin-V binds to exposed phosphyltidylserine on
the extracellular membrane in a calcium-dependent fashion and
has been shown to label degenerating retinal ganglion cell axons
and soma after experimental anterior ischemic optic neuropathy
(AION). Because the labeling of degenerating axons with annexin-V
is relatively labile, in this study, we determine whether inclusion
of calcium in different experimental steps helps to enhance axonal
labeling.
Methods: We induced optic nerve head ischemia in adult C57BL/6
mice using laser-assisted photochemical thrombosis. After one
week, we performed intravitreal injection of annexin-V-A488 and
imaged the retina 2-3 hours later using confocal scanning laser
ophthalmoscopy (cSLO) and optical coherence tomography (OCT).
Then, we prepared retinal whole mount in calcium-free or 2.5
mM CaCl2 conditions and imaged the retinae using fluorescence
microscopy for up to 7 days after mounting.
Results: On the day of annexin-V-A488 labeling, degenerating axons
were easily seen in both Ca2+-containing (N = 30) and Ca2+-free (N
= 10) conditions. Annexin-V-A488 labeling of degenerating axons
one week after ischemia correlated well with the presence of optic
nerve swelling on day-1 as measured by OCT. No annexin-V-A488
labeling of axons was seen in the control eyes (N = 6), which showed
no swelling on OCT. Inclusion of Ca2+ to the fixative, wash, and
mounting solutions significantly improved the persistence of annexinV-A488 signal one to seven days after labeling. In contrast to the
difficulty of preserving axonal labels, bright annexin-V-A488 signal
on degenerating soma was easily seen even one week after labeling.
We used these brightly labeled soma to test the lability of annexinV-A488 labeling over 5, 10, and 20 min of light exposure and found a
dramatic, time-dependent decrease in fluorescence signal, consistent
with the relative lability of the annexin-V-A488 signal.
Conclusions: Annexin-V-A488 brightly labels degenerating retinal
ganglion cell axons one week after experimental anterior ischemic
optic neuropathy, and the presence of 2.5 mM Ca2+ during retinal
tissue preparation helps preserve this relatively labile label. During
microscopy, even minutes of bright light exposure can quench
annexin-V-A488 signal, and every effort should be made to shield the
tissue from bright light during experimentation.
Commercial Relationships: Gun Ho Lee, None; M Ali Shariati,
None; Ming-Hui Sun, None; Yaping J. Liao, None
Support: Stanford Undergraduate Advising and Research Grant, Vice
Provost for Undergraduate Education Grant
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 5541 Poster Board Number: B0112
Presentation Time: 8:30 AM–10:15 AM
Rapamycin rescues the innate immune/inflammatory response in
the retina of the Ndufs4 mouse
Alfred K. Yu1, Lanying Song1, Karl Murray2, Gino Cortopassi1. 1Vet
Med: Molecular Biosciences, University of California, Davis, Davis,
CA; 2Center for Neuroscience, University of California, Davis, Davis,
CA.
Purpose: Mitochondrial complex I dysfunction has been shown to
lead to vision loss via the loss of function of retinal ganglion cells
(RGCs), however the mechanism of which that occurs in unclear.
A recent study has shown that rapamycin treatment of Ndufs4
deficient mice alleviates mitochondrial disease and prolongs the life
expectancy of these mice by reducing mTOR signaling. The goal of
this study is to see the effects of rapamycin treatment in the retina of
these mice by evaluating innate immune and inflammatory transcripts
that we have already seen to increase in the Ndufs4 KO mouse. This
will be valuable in developing therapeutics for mitochondrial visual
diseases, such as Leber’s hereditary optic neuropathy (LHON) and
Autosomal dominant optic atrophy (ADOA).
Methods: Two Ndufs4 KO and two wild type controls received
intraperitoneal injection (IP) of rapamycin (8mg/kg) daily for nine
days starting from P22. Additionally, two Ndufs4 KO and two wild
type controls received IP injection of vehicle. Experiments were
conducted in compliance with the ARVO Statement for the Use of
Animals in Ophthalmic and Visual Research. After nine days of
treatment the nice were sacrificed and the retinas were surgically
removed and placed in RNALater. Total RNA was extracted from the
retinas and cDNA was synthesized for evaluation by qRT-PCR. The
primers tested include: Fas, Tlr4, Ccl5, Ccl12, C1ra, Tlr3, Mmp12,
Icam1, Cxcl9, Aif1, Tlr2, Cd68, C1qc, B2m, and Cxcl10. Analysis
was done by calculating the delta delta Ct and statistical significance
was determined by student’s t-test (2 tailed; equal variance).
Results: Of the inflammatory transcripts tested, 16 out of 16
transcripts showed mean elevation compared to wild type
controls, as was previously seen. Treatment with rapamycin
inhibited the inflammatory response and the mean levels of all 16
transcripts rebounded and returned to values similar to wild type
control, indicating that rapamycin suppresses inflammation that
is downstream of mitochondrial dysfunction and may prevent
neurodegeneration.
Conclusions: In the Ndufs4 retinal, mitochondrial complex I
deficiency leads to vision loss, which is mediated by an innate
immune and inflammatory response. Systemic treatment with
rapamycin rescues this innate immune and inflammatory response
and may prevent RGC death-mediated vision loss. This will provide
therapeutic insight in mitochondrial diseases such as LHON and
ADOA
Commercial Relationships: Alfred K. Yu, None; Lanying Song,
None; Karl Murray, None; Gino Cortopassi, None
Support: NH Grant EY012245
Program Number: 5542 Poster Board Number: B0113
Presentation Time: 8:30 AM–10:15 AM
Microglial activation in a rat model of NAION
Anne-Laure Remond1, Audrey Fel1, Manuel SIMONUTTI2, Ivana
IVKOVIC2, Jose A. Sahel2, Phuc LeHoang1, Bahram Bodaghi1, Serge
A. Picaud2, Valerie Touitou1. 1Ophthalmology, Pitie Salpetriere, Paris,
France; 2Vision Institut, Paris, France.
Purpose: Non arteritic anterior ischemic optic neuropathy
(NAION) is the most common optic neuropathy over 50 years and
its pathophysiology remains controversial. Activation of retinal
microglial cells (RMC) is known to contribute to retinal ganglion cell
(RCG) death after optic nerve injury. The purpose of this study was to
investigate early microglial activation and the effect of minocycline
on this activation in a rat model of NAION (rNAION).
Methods: We used a rNAION model to generate axonal ischemic
infarct by rose Bengal dye laser photoactivation. NAION was
induced in the right eye (RE) of each animal. One group of animals
received minocycline (22 mg/kg) intraperitoneally and a second
group received a sham injection of saline, 3 days before induction
till sacrifice. Animals were euthanazied at day 1, 3 and 7 after laser
photoactivation. Immunohistochemistry and quantitative stereology
of RCG (Brn3a positive cells) and RMC (IBA-1positive cells) were
performed on flat-mounted retina. Expression levels of IBA-1,
apoptosis-related genes (Bax, caspase 3) and vascular growth factor
related genes (VEGF-a) were measured by qPCR.
Results: A significant increase in the number of RMC was observed
with stereology on flat-mounted retina in eyes with NAION, at day
1, 3 and 7 after induction. The expression of Iba-A, a microglia/
macrophage-specific calcium-binding protein, measured by qPCR,
was statistically increased in the eyes with NAION, at day 3 for
both groups (minocycline and saline) and at day 7 for the group
treated with minocycline (p<0,05). This expression was higher
with minocycline at day 3 and 7. The expression of caspase was
significantly increased (p <0.05) in NAION eyes at day 3 in the group
treated with minocycline and VEGF-A tended to have an increased
expression in the group with saline at day 3 and 7 (p>0.05). There
was no difference in the expression of Bax between the two groups.
Conclusions: Our results demonstrate that microglia is activated
early in the course of NAION and contribute to retinal ganglion
cell death after NAION. The presence of an increased number of
activated microglial cells in the eyes with NAION of animals treated
with minocyclin is unexpected considering the supposed effect of
minocyclin. However, microglial cells include a broad spectrum of
populations and minocycline could modulate one of these subpopulations with a protective effect on ganglion cells after the stroke
thus promoting RGC survival.
Commercial Relationships: Anne-Laure Remond, None; Audrey
Fel, None; Manuel SIMONUTTI, None; Ivana IVKOVIC, None;
Jose A. Sahel, None; Phuc LeHoang, None; Bahram Bodaghi,
None; Serge A. Picaud, None; Valerie Touitou, None
Program Number: 5543 Poster Board Number: B0114
Presentation Time: 8:30 AM–10:15 AM
Lucentis is Not Neuroprotective in a Primate Model of NonArteritic Anterior Ischemic Optic Neuropathy (NAION)
Mary A. Johnson1, Neil R. Miller2, Steven L. Bernstein1. 1Ophthal and
Vis Science, Univ of Maryland Sch of Medicine, Baltimore, MD;
2
Ophthalmology, Johns Hopkins Univ. Sch. Med., Baltimore, MD.
Purpose: Non-Arteritic Anterior Ischemic Optic Neuropathy
(NAION) is the most common cause of acute optic nerve-related
vision loss in people over 50. There is no treatment. A retrospective
study (Saati et al., 2013) and 2 small case studies (Bennett et al.,
2007; Bajin et al., 2011) suggested that a single intravitreal (IVT)
injection of ranibizumab protects against vision loss in NAION. A
Genentech-supported clinical trial was completed in 2012; the results
have not been announced. The relatively rare nature of the disorder
and the 40% incidence of spontaneous improvement (IONDT, 1995)
are challenges for NAION clinical studies. For this reason, we tested
the efficacy of a single IVT injection of ranibizumab (Lucentis) in our
primate model of NAION (pNAION).
Methods: Four normal male rhesus monkeys (8 - 12kg) were given
a single IVT injection of Lucentis (1.25mg in 0.05ml) immediately
following induction of experimental NAION (Chen & Johnson et al.,
2008) in one eye. Four weeks later the fellow eye was induced and
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
injected with a single IVT dose of vehicle. Spectral-domain OCT
(Heidelberg, Inc), flash electroretinograms (ERGs), and simultaneous
pattern ERG (pERG) and pattern visual evoked potentials (VEPs)
were recorded, and fundus photography and fluorescein angiography
(FA) were performed on each animal before and at 1 day, 1 week, 2
weeks, 4 weeks and 8-12 weeks after induction of pNAION. Animals
were sacrificed within 2 weeks of final assessment. Differences in the
retinal ganglion cell (RGC) numbers in each eye were estimated by
stereological analysis of optic nerve axons. Optic nerve axons, myelin
and inflammatory cells were evaluated using immunohistochemistry.
Results: Lucentis conferred no advantage to the treated eye in
development or resolution of macular (p = 0.45) or peripapillary
edema (by OCT), in retention of VEP (p = 0.19) and pERG (p =
0.28) amplitudes, in the time course of optic nerve leakage and
fluorescein dye staining, or in preservation of RGCs, compared with
vehicle controls. Three of the 4 Lucentis-treated eyes showed more
peripapillary leakage and eventual atrophy than the vehicle-treated
eyes.
Conclusions: IVT administration of Lucentis showed no evidence
of neuroprotection in a primate model of NAION, despite maximal
dosing and immediate treatment post-induction. This finding suggests
that VEGF inhibition is likely to be ineffective in clinical NAION
treatment.
Commercial Relationships: Mary A. Johnson, None; Neil R.
Miller, None; Steven L. Bernstein, None
Support: NIH Grant EY019529
Program Number: 5544 Poster Board Number: B0115
Presentation Time: 8:30 AM–10:15 AM
Characterization and application of a nonhuman primate
model of non-arteritic anterior ischemic optic neuropathy for
therapeutic screening
Matthew S. Lawrence1, Jordan Attwood1, Alex Lewis1, Rohn Brookes1,
Vernard Woodley1, Meghan Tucker1, Wenzheng Hu1, Robin J. Goody1,
Sean Callanan2, Demetrios Vavvas3. 1Research, RxGen, Hamden, CT;
2
Ross University, Basseterre, Saint Kitts and Nevis; 3Massachusetts
Eye and Ear Infirmary, Boston, MA.
Purpose: To characterize the nature and time course of optic nerve
and retinal pathology following induction of non-arteritic anterior
ischemic optic neuropathy (NAION) by focal photothrombotic insult
to the optic nerve head (ONH) in African green monkeys, and to
evaluate the effect of candidate neuroprotective agents in reducing
the elicited pathology.
Methods: Fifteen adult monkeys received unilateral ONH laser
treatment (wavelength 532mm; power 100mW; spot size 500mm;
duration 9 seconds x 4), immediately following intravenous
administration of rose bengal (0.1 ml/kg of 25 mg/kg) to induce
oxidative endothelial injury of ONH microvasculature. Eyes
were evaluated by slit lamp exam, color fundus photography,
fluorescence angiography, optical coherence tomography (OCT)
and electroretinography (ERG) at baseline and days 1, 7, 14, 28, 56
and 84 post-laser. Apoptosis and necrosis inhibitors or vehicle were
administered intravitreally immediately following laser treatment.
Results: Photothrombotic injury to the ONH employing the applied
laser parameters consistently triggered the onset and evolution of
a pathology very similar to clinical NAION, with ONH edema
within 24 hours, followed by retinal venous stasis, peripapillary
hemorrhages, and optic nerve fiber layer (ONFL) thickening over the
ensuing week, which gradually resolved, leaving residual ONH pallor
and ONFL thinning. Electrophysiological changes were correlated
with ONFL changes detectible by OCT. Terminal histology findings
were additionally correlated with in-life exam findings. Intervention
with pan-caspase and receptor interacting protein 1 kinase inhibitors
at the doses explored positively modulated endpoints, although
demonstration of statistically significant therapeutic effect was
limited by sample size.
Conclusions: Photothrombotic NAION in the green monkey exhibits
pathological changes very similar to the human condition with early
onset ONH and retinal edema followed by ONFL thinning with
associated ERG changes indicative of functional deficit, all of which
can be evaluated in a quantitative, longitudinal manner. This supports
application of the model as a test system to further understand
the pathophysiology of NAION and the evaluation of candidate
therapies, the utility of which as been demonstrated in our initial
exploration of the therapeutic effect of cell death pathway inhibitors.
Commercial Relationships: Matthew S. Lawrence, RxGen (F);
Jordan Attwood, RxGen (F); Alex Lewis, RxGen (F), RxGen (F),
RxGen (F); Rohn Brookes, RxGen (F); Vernard Woodley, RxGen
(F); Meghan Tucker, RxGen (F); Wenzheng Hu, RxGen (F); Robin
J. Goody, RxGen (F); Sean Callanan, None; Demetrios Vavvas,
None
Support: NEI 1 R43 EY023867-01
Program Number: 5545 Poster Board Number: B0116
Presentation Time: 8:30 AM–10:15 AM
Risk factors associated with nonarteritic anterior ischemic optic
neuropathy in young patients at a reference center in Mexico City
SECTION: Eye Movements/Strabismus/Amblyopia/Neuroophthalmology (EY)
Mariana A. Flores, Laura Andrea Torrado, Mayra F. Camargo.
Ophthalmology, Instituto de Oftalmologia, Mexico City, Mexico.
Purpose: Nonarteritic anterior ischemic optic neuropathy remains
a diagnosis for people older than 50 years old. We aim to describe
the demographic characteristics and risk factors associated with
nonarteritic anterior ischemic optic neuropathy in patients younger
than 50 years old in a reference center in Mexico City.
Methods: Retrospective analysis of the medical records of all
the patients diagnosed with nonarteritic anterior ischemic optic
neuropathy from September 2007 to November 2014 in a reference
center in Mexico City. We include age, sex, best-corrected visual
acuity and comorbilities associated. We exclude those patients with
an incomplete record.
Results: We found 1967 medical records with the diagnosis of
nonarteritic anterior ischemic optic neuropathy. 177 patients were
younger than 50 years old (ranged: 2 -49 years-old). 110 females 67
males. 23.16% presented dyslipidemia (41 patients), 22.60% with
diabetes mellitus type 2 (40 patients) and 19.77% primary systemic
hypertension (35 patients). Thirteen patients (7%) presented with a
history of trauma, 4.51% (8 patients) with hemorrhagic or ischemic
cerebral vascular event and 2.8% with a cerebral tumor (5 patients).
In the group of patients younger than 30 years old a repetitive
antecedent of neonatal hypoxia was found (12 patients, 6.7%) and
only one case with hereditary optic neuropathy.
Conclusions: In this study we found that the comorbidity such
as dyslipidemia, diabetes mellitus and hypertension represented
the most significant risk factors for presenting with nonarteritic
ischemic optic neuropathy. This is the first information obtained
in latinamerican population. We believe that the Mexican diet and
lifestyle could have an important impact in its development and more
studies need to be done.
Commercial Relationships: Mariana A. Flores, None; Laura
Andrea Torrado, None; Mayra F. Camargo, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 5546 Poster Board Number: B0117
Presentation Time: 8:30 AM–10:15 AM
50% of Non-Arteritic Anterior Ischemic Optic Neuropathy
Occurs between 40-55 Years Old
Ming-Hui Sun1, 2, Yaping J. Liao1, M Ali Shariati3. 1Ophthalmology,
Byers Eye Institute Stanford University, Palo Alto, CA;
2
Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical
Center, Kweishan, Taoyuan, Taiwan; 3Ophthalmology, Stanford
University school of Medicine, Palo Alto, CA.
Purpose: Non-arteritic ischemic optic neuropathy (NAION) is the
most common acute optic neuropathy in those older than 50. and
young onset NAION has been reported in 4-23% of patients. The
aim of our study is to investigate the age of onset of NAION and
correlation with risk factors.
Methods: We performed a retrospective review at a single institution
of consecutive patients with the diagnosis of NAION (2009-2014)
who had neuro-ophthalmic evaluation, automated static perimetry,
and optical coherence tomography (OCT).
Results: We studied 50 NAION eyes in 32 patients (24 male, 8
female; unilateral: 14 patients, bilateral: 18 patients). The average age
of first events was 54.6±2.4 years (median 54 years; ≤50: 11 (33.7%)
patients, >50: 20 (66.3%) patients; range 24-80 years). In fact, 50%
of patients presented with their first event between ages 40-55. In
all ages, AION led to significant visual field loss (mean deviation
AION: -14.1±1.5 dB; control: -1.6±0.5 dB; P<0.001, Mann-Whitney)
and significant thinning of thickness of the retinal nerve fiber layer
(AION: 66.0±3.9 mm; control: 89.9±4.6 mm; P<0.001) and macular
ganglion cell complex as measured by OCT (AION: 61.7±1.8 mm;
control: 82.4±3.4 mm, P<0.001). In terms of AION risk factors, all
age groups had small optic disc area (mean optic disc area 1.65± 0.30
mm2, N = 43 eyes), obstructive sleep apnea (≤50: 82%, average AHI
27.9±7.9; >50: 80%, average AHI 24.6±7.7), and vascular risk factors
(hypertension, diabetes, hyperlipidemia). Treatment for obstructive
sleep apnea did not prevent future events but was associated with
delayed onset of new events (treated: 63.5±54.9 months, median
10 months; not treated: mean 21.6±16.4 months, median 5 months;
P=0.2). The presence of optic disc drusen was associated with earlier
onset of AION by 2 decades (N=2 patients, 3 affected eyes), but
all affected eyes had final visual acuity of 20/20. Consistent with
this finding, age may be an important factor in visual prognosis,
since those ≤50 years old at first event had a trend of better final
visual acuity, visual field mean deviation, and OCT retinal thickness
measurements than those >50.
Conclusions: Fifty percent of NAION patients had onset of first
event at 40-55, so age greater than 40 should be considered the
common presentation of NAION. Age may also be an important
factor in NAION prognosis, since younger patients had better visual
outcome.
Commercial Relationships: Ming-Hui Sun, None; Yaping J. Liao,
None; M Ali Shariati, None
Program Number: 5547 Poster Board Number: B0118
Presentation Time: 8:30 AM–10:15 AM
Nocturnal Diastolic Blood Pressure decrease under 50mmHg is a
risk factor for Nonarteritic Anterior Ischemic Optic Neuropathy
in elderly patients
thibaut Chapron1, 2, Fouzia Mantout1, Sylvie Feldman1, marie
helene errera3, Laurence Du Pasquier1, Isabelle Rossignol1, Rabah
Benrabah1, Emmanuel Heron1. 1Internal medicine, Hopital Quinze
Vingt, Paris, France; 2Université Paris Descartes, Paris, France;
3
Ophthalmology 4, Hopital Quinze Vingt, Paris, France.
Purpose: To analyze 24-hours Arterial Blood Pressure (ABP)
recordings in elderly patients with Nonarteritic Anterior Ischemic
Optic Neuropathy (NAION) compared with other retinal vascular
diseases.
Methods: Over a 7-year period, 49 NAION patients and 27 control
subjects with sudden visual loss due to arterial, venous or diabetic
retinal vascular acute episodes, all aged 70 or more, underwent
24-hours ABP recordings. Our main outcome was the number of
patients with one or more nocturnal diastolic ABP fall under 50
mmHg. Number of patients with one or more nighttime systolic
ABP fall under 90 mmHg, mean systolic and diastolic ABP during
24-hours, daytime and nighttime, as well as standard NAION risk
factor were also studied.
Results: Nocturnal diastolic ABP values ≤50 mmHg were observed
in 20 (41%) NAION and 4 (15%) control subjects (P=0.02).
Nocturnal systolic ABP values ≤90 mmHg were observed in 5 (10%)
NAION and 4 (15%) control subjects (p=0,55). Mean systolic(SD)/
diastolic(SD) 24-hour ABP was 134(17)/70(9) mmHg in NAION
and 135(20)/71(10) mmHg in control subjects (P=0.78). No statistic
difference was observed regards of mean systolic and mean diastolic
ABP whether in daytime or nighttime recordings. 23 (46%) NAION
and 19 (70%) control subjects took hypotensive drug therapy
(p=0.04). Sex ratio, body mass index, and the frequency of diabetes
and dyslipidemia were not different.
Conclusions: Nocturnal diastolic ABP fall under 50mmHg, a risk
factor for cerebral hypoperfusion, is significantly more frequent in
elderly patients with acute visual loss due to NAION compared with
other vascular retinal etiologies, and appears to be a specific risk
factor for this disease.
Commercial Relationships: thibaut Chapron, None; Fouzia
Mantout, None; Sylvie Feldman, None; marie helene errera,
None; Laurence Du Pasquier, None; Isabelle Rossignol, None;
Rabah Benrabah, None; Emmanuel Heron, None
Program Number: 5548 Poster Board Number: B0119
Presentation Time: 8:30 AM–10:15 AM
MMP19 Expression in the Human Optic Nerve
Ralph Hazlewood1, 2, Kathy Miller1, 2, Robert F. Mullins1, 2, Markus
H. Kuehn1, 2, Lee M. Jampol3, John H. Fingert1, 2. 1Ophthalmology
and Visual Sciences, University of Iowa, Iowa City, IA; 2Stephen A.
Wynn Institute for Vision Research, Iowa City, IA; 3Ophthalmology,
Feinberg School of Medicine, Northwestern University, Chicago, IL.
Purpose: We previously linked MMP19 mutations with a congenital
malformation in which the optic disc is deeply excavated known
as cavitary optic disc anomaly (CODA). The purpose of this study
was to investigate the expression of MMP19, a secreted matrix
metalloproteinase, within the optic nerve.
Methods: MMP19 protein expression in the optic nerve was
evaluated by immunohistochemistry in sagittal and en face sections
of optic nerves obtained from normal human donor eyes. Sections
were co-labeled with antibodies directed against glial cells (GFAP),
ganglion cell axons (βIII Tubulin), and microglia (CD45). All
experiments were conducted in triplicate using three different human
donor eyes.
Results: MMP19 immunolabeling was observed throughout the optic
nerve including the optic nerve head. Expression was highest in the
prelaminar region and laminar region, with much lower levels in the
retrolaminar region. Differential MMP19 labeling was also observed
in the cross-sections of the optic nerve, with increased signal in
the periphery or edges towards the scleral canal and pia mater.
Additionally, no significant co-localization was observed between
MMP19 and markers of glial cells, ganglion cell axons, or microglia.
Conclusions: Immunohistochemical analysis shows that MMP19
is strongly expressed in the optic nerve head of human donor
eyes, the primary site of pathology in CODA patients. No obvious
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
co-localization was observed with markers for cell types that
populate the optic nerve, suggesting that MMP19 accumulates
primarily within extracellular spaces in the optic nerve. Moreover,
the lateral localization of MMP19 within the optic nerve suggests
that dysregulation of its enzymatic function might undermine the
adhesion between the optic nerve and the scleral canal and promote
formation of an excavated optic nerve head – the key feature of
CODA.
Commercial Relationships: Ralph Hazlewood, None; Kathy
Miller, None; Robert F. Mullins, None; Markus H. Kuehn, None;
Lee M. Jampol, None; John H. Fingert, None
Support: NIH (Grants R21 EY24621, R01EY018825,
R01EY023512) to J.H.F and the Dean’s Graduate Fellowship, the
University of Iowa to R.J.H.
Program Number: 5549 Poster Board Number: B0120
Presentation Time: 8:30 AM–10:15 AM
Artificial Intelligence Methods are robust and useful techniques
to classify optic nerve fibers using its morphometric parameters
Joaquin De Juan1, Jose L. Girela2, David Gil3, Noemi Martínez-Ruiz2,
Jorge Azorin3, Bassima Boughlala2. 1Biotechnology, Universidad
de Alicante, San Vicente del Raspeig, Spain; 2Biotechnology,
Universidad de Alicante, Alicante, Spain; 3Computer Technology,
Universidad de Alicante, Alicante, Spain.
Purpose: The rat optic nerve axons come from the retinal ganglion
cells. Only a few of them have their origin in the pretectal area. The
diameters of the optic nerve axons are far from being a homogeneous
population. There are at least three main groups of ganglion cells in
rat retinas and three different axon types in the rat optic nerve. The
morphometric study of optic nerve fibers is a useful tool to research
the function, development, aging and pathological conditions of
them. Thus, classification of the optic nerve axons is crucial in
order to make experimental comparisons. The aim of this work is
to classify the optic nerve axons by analyzing their ultrastructural
parameters with Artificial Intelligence (AI) methods.
Methods: Adult albino Wistar rats were anesthetized, transcardially
perfused and its optic nerves removed and processed for
ultrastructural microscopy studies. Optic nerve axons were analyzed
with a computer-linked planimeter. Several parameter, were obtained
for each axonal cross-section using a computer program. The
parameters were: axon diameter, axon area, myelin sheath thickness,
G-Ratio, microtubule number (MTn), neurofilament number (NFn)
and R-proportion (R = NFn/[NFn+MTn]). Data were processed
with a set of AI methods, two supervised techniques, Multilayer
Perceptron (MLP) and Decision Trees (DT), and other unsupervised
one, K-Means clustering. All the computations of the decision tree
were developed using the WEKA software (Machine Learning Group
at the University of Waikato).
Results: Using k-means clustering analysis we were able to
identify three different groups of fibers in the optic nerve, which
are consistent with the results obtained in functional studies. The
main parameters that allowed us the classification of optical nerve
fibers were axon diameter, G-Ratio, and R-proportion. Using these
parameters, we analyzed the classification accuracy of MLP and
DT, as tools to develop an automated system. In both cases, the
Classification Accuracy was above 95%, being higher with the MLP
technique that reached a 98.9% of accuracy.
Conclusions: Results show that morphometric parameters can be
used to identify different populations of nerve fibers, with a high
accuracy when AI methods are used. Only a limited number of
parameters are needed to produce a consistent classification. The
MLP technique is the most useful.
Commercial Relationships: Joaquin De Juan, None; Jose L.
Girela, None; David Gil, None; Noemi Martínez-Ruiz, None;
Jorge Azorin, None; Bassima Boughlala, None
Support: Vicerrectorado de Innovación, University of Alicante,
Spain (Vigrob-137)
Program Number: 5550 Poster Board Number: B0121
Presentation Time: 8:30 AM–10:15 AM
Lamina Cribrosa Position Changes with the Valsalva maneuver
Keegan Harkins1, Sachin Kedar1, Yasir J. Sepah1, Mohammad A.
Sadiq1, Justin West2, Deepta Ghate1. 1Ophthalmology, University
of Nebraska Medical Center, Omaha, NE; 2College of Medicine,
University of Kentucky, Lexington, KY.
Purpose: The Valsalva maneuver (VM) causes an increase in
intraocular pressure (IOP) and intracerebral pressure (ICP). This
prospective clinical study aimed to test if acute changes in ICP and
IOP can cause changes in the lamina cribrosa (LC) position.
Methods: The study population had 20 healthy volunteers from the
University of Kentucky. VM was performed with a manometer and a
mouth pressure of 30-33 cm of H2O held for 15 seconds. The Icare®
tonometer was used to check IOP before and during the VM (after 15
seconds). The Spectralis OCT® was used to acquire 12 radial optic
nerve head images before and during the VM (after 15 seconds).
There was a 10 minutes gap between right and left eye measurements
and between the IOP and OCT acquisition. 3 of the 12 radial OCT
sections (selected by expert grader) were independently graded by 2
graders for anterior lamina cribrosa depth (LCD), Bruch’s membrane
opening width (BMO) and cup depth from BMO plane. Any image
with a measurement discrepancy>40 mm was re-graded by the expert
grader.
Results: The mean age was 29±4.7 years with 40 eyes analyzed
There was no significant change in BMO depth (mean change
-3.7±37.5 mm), cup depth (mean change -1.3±24.1 mm) and LC depth
(mean change -0.3±31.4 mm) with the VM. IOP increased with the
VM in all eyes (mean change3.2±2.2 mmHg, p<0.05). 20 eyes had
anterior LC shift with the VM (mean LC position change -20.9±13.6
mm). 14 eyes had LC posterior shift (mean LC position change
-29.2±28.2 mm). 2 eyes had no change in LC position and 4 eyes
had ungradable LC. Mean IOP change was significantly (p<0.05)
higher with anterior LC shift (3.65 mm Hg) versus posterior LC shift
(2.93 mm Hg). There was no significant difference in IOP change
with BMO widening versus shortening and in anterior and posterior
cup depth shift. There was no significant association between BMO
widening or shortening and anterior or posterior LC shift. There was
a significant association between anterior and posterior shift of the
LC and cup depth (chi square=4.37, p< 0.05).
Conclusions: Despite an IOP rise in all eyes, the VM causes anterior
LC shift in 50% of eyes. This anterior LC shift is associated with
higher IOP change and an anterior shift of the cup depth but not with
BMO width changes. The eyes with anterior LC shift presumably
had a rise in ICP> IOP which would presume that the LC position
changes with fluctuations in ICP.
Commercial Relationships: Keegan Harkins, None; Sachin
Kedar, None; Yasir J. Sepah, None; Mohammad A. Sadiq, None;
Justin West, None; Deepta Ghate, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 5551 Poster Board Number: B0122
Presentation Time: 8:30 AM–10:15 AM
Color-Fundus-Feature-Based Prediction of Regional SD-OCTBased ONH-Volume in Optic Nerve Edema
Jason Agne1, Jui-Kai Wang1, Randy H. Kardon2, 3, Mona K. Garvin2, 1.
1
Department of Electrical and Computer Engineering, The University
of Iowa, Iowa City, IA; 2Center for the Prevention and Treatment
of Visual Loss, Iowa City VA Health Care System, Iowa City, IA;
3
Department of Ophthalmology and Visual Sciences, The University
of Iowa, Iowa City, IA.
Purpose: Optic nerve edema is commonly assessed via direct
funduscopic observation or digital fundus photographs using a
six-stage Frisén grading scale. While 3D image-analysis of spectraldomain optical coherence tomography (SD-OCT) can provide
volumetric measures of optic nerve head (ONH) swelling (Wang
et al., IOVS 2012), developing automated objective quantitative
measures of the degree of swelling is important in situations where
SD-OCT is not commonly available, such as in emergency rooms.
The purpose of this work is to develop and evaluate a machinelearning approach for the prediction of regional SD-OCT volumetric
measures from color-fundus-photographic features.
Methods: Our previously developed 3D image-analysis approach
was used to measure regional (nasal, superior, temporal, and inferior
regions within 1.73 mm of the center of the ONH) from 48 ONHcentered SD-OCT volumes (Zeiss Cirrus) of 48 patients with varying
stages of optic nerve edema (Figure 1a,b). Features concerning the
boundary of the ONH swelling (such as the area of the bounded
region and the smoothness of the boundary), global and local texture
features (such as joint entropy of various image transformations and
local entropy of the area bounded by the ONH swelling), and vessel
features (such as edge derivative values, and a measure of vessel
discontinuity) were extracted from color fundus photographs taken
on the same day (Figure 1c) using our automated approach, and used
in a leave-one-patient-out random forest regression to predict the
volumetric information for each region of the SD-OCT image.
Results: Pearson correlation coefficients of Rnasal = 0.74, Rsuperior =
0.66, Rtemporal = 0.68, and Rinferior = 0.67 were obtained between our
fundus-based predicted measures and the actual SD-OCT-based
regional measures. Scatter plots are shown in Figure 2.
Conclusions: Regional 3D volumetric information can be predicted
from 2D fundus information and demonstrates the feasibility of
objectively and quantitatively measuring optic nerve edema from
fundus photographs alone.
From top to bottom: (a) Example 3D rendering of top surface from
SD-OCT image with the primary region indicated. (b) Computed
volumetric measures of ONH displayed on a thickness map. (c)
Corresponding fundus image.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Results: There was a correlation between the amplitude of the
mfPhNR and Central Lineal Visual Sensitivity in the inferior
(R=0.456, P=0.012). On the other hand, there was no correlation
between the amplitude of the mfPhNR and Central Lineal Visual
Sensitivity in the superior (R= 0.332, P= 0.068).
Conclusions: We presented previously that there was a strong
correlation between the amplitude of mfPhNR and Lineal Visual
Sensitivity in about 20 degrees. There was less correlation between
the amplitude of mfPhNR and Lineal Visual Sensitivity in about 10
degrees.
Commercial Relationships: Ari Kamei, None; Eiichiro Nagasaka,
None
The volume for each sub-region as predicted from this method
plotted against the volume for each sub-region as computed with a
segmentation of SD-OCT images
Commercial Relationships: Jason Agne, None; Jui-Kai Wang,
None; Randy H. Kardon, Acorda (C), Department of Veterans
Affairs Research Foundation, Iowa City, IA (S), Fight for Sight Inc
(S), Novartis (C); Mona K. Garvin, The University of Iowa (P)
Support: R01 EY023279
Program Number: 5552 Poster Board Number: B0123
Presentation Time: 8:30 AM–10:15 AM
Multifocal Photopic Negative Response (mfPhNR) and Central
Lineal Visual sensitivity in Patients with Optic Nerve Lesions
Ari Kamei1, Eiichiro Nagasaka2. 1Ari Eye Clinic, Oshu-Mizusawa,
Japan; 2Mayo Corp., Inazawa, Japan.
Purpose: To evaluate the interrelation of mfPhNR and Central Lineal
Visual Sensitivity in superior and inferior in patients with optic nerve
lesions.
Methods: Thirteen eyes of thirteen volunteers with normal vision
and eighteen eyes of nine patients with optic nerve lesions including
normal tension glaucoma (NTG) were tested.
The mfPhNR was recorded with the VERIS Science System 5.0.4.
The visual stimulus was made up of 37 hexagons in an approximately
40-degree visual field, Pseudo-randomly alternating between black
(5cd/m2) and white (200cd/m2) on the CRT monitor. Burian-Allen
ERG Electrodes, Adult-bipolar or Pediatric-bipolar, were used for
this testing. The recording time was approximately 8 min. with
dilated pupils having the best-corrected visual acuity. The band pass
filter of the amplifier was set from 1 to 100 Hz. The amplification
and stimulus frequency were set to 10000 and 9.41 Hz (8 frames)
respectively.
Each trace of the mfPhNR found in superior and inferior regions was
analyzed in about 10 degrees.
The static visual field was examined with a central 30-2 SITA
Standard program using a Humphrey Field Analyzer. The mean
deviation (dB) in 10 degrees was converted to lineal visual sensitivity
(1/Lambert) to apply for the analysis.
Program Number: 5553 Poster Board Number: B0124
Presentation Time: 8:30 AM–10:15 AM
OPTIC ATROPHY IN CLASSICAL METHYLMALONIC
ACIDEMIA
JOYCE MBEKEANI2, 1, Hachemi Nezzar3, 4, Ola Al Ali5, Zahra
Al Sahlawi5, Abdelmoneim Eldali6, Mohammed Al Owain5.
1
Ophthalmology & Visual Sciences, Albert Einstein College of
Medicine, Bronx, NY; 2Surgery, North Bronx Health Network, Bronx,
NY; 3Ophthalmology, King Faisal Specialist Hospital & Research
Center, Riyadh, Saudi Arabia; 4Ophthalmology, Centre Hospitalier
Universitaire, Clermont Ferrand, France; 5Medical Genetics, King
Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia;
6
Biostatistics, King Faisal Specialist Hospital & Research Center,
Riyadh, Saudi Arabia.
Purpose: Methylmalonic acidemia (MMA) is an autosomal recessive
disorder resulting in failure to process various amino acids and lipids.
The classical form results in methylmalonyl CoA mutase deficiency,
preventing the Vit B12-dependent conversion of methylmalonyl CoA
to succinyl CoA, required in Krebs cycle. Patients typically present
in early infancy with lethargy, vomiting, dehydration and failure
to thrive. Long-term complications include renal failure (CRF),
encephalopathy and pancreatitis. 4 cases of optic atrophy (OA) have
been reported in classical MMA on appropriate dietary restrictions.
The exact etiology is unknown but likely is multi-factorial. With
improved survival of patients offered advanced treatment, OA needs
to be identified so that prophylactic/therapeutic intervention, when
available, can be incorporated into management protocols. The
purpose of this observational study is to identify and determine the
prevalence of OA in a small cohort of patients with classical MMA.
Methods: 22 patients clinically diagnosed and genetically
confirmed to have classical MMA were assessed with full history,
neuroophthalmic exam, fundus photos and visual evoked potentials
(VEP). Diagnosis of OA was determined by a combination of visual
acuity, pupil reactions, optic nerve appearances, OCT and VEP.
Associations of tabulated data were determined using Mann-Whitney
U, Kruskal-Wallis, Chi-squared and Fisher’s exact tests.Statistical
significance was set at p<0.05. Patients with proprionic acidemia and
intracellular cobalamin metabolism disorders, which have clinical
features of MMA were excluded.
Results: 8 patients were female and 14, male. Age range was 7
to 27yrs (median=14;IQR=11-16).13 patients (59%) had OA;
85% of these were bilateral. 6 (46.15%) reported decreased
vision and 7 (53.85%) were asymptomatic.12 patients had CRF
(median=16;IQR=14.5-20). Age was not significantly associated with
OA (p=0.17) but significantly related to CRF (p=0.0067). Patients
with OA were more likely to have CRF than those without OA
(p=0.0058).
Conclusions: Optic atrophy is a frequent finding in classical
MMA and most commonly is bilateral and sub-clinical. A positive
correlation with CRF, known independently to be associated with
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
OA, suggests a contributing causal relation. These findings have
important clinical and management implications: early and periodic
ophthalmic exams including VEP and OCT should be performed in
all, including asymptomatic patients with MMA.
Commercial Relationships: JOYCE MBEKEANI, None;
Hachemi Nezzar, None; Ola Al Ali, None; Zahra Al Sahlawi,
None; Abdelmoneim Eldali, None; Mohammed Al Owain, None
Program Number: 5554 Poster Board Number: B0125
Presentation Time: 8:30 AM–10:15 AM
Optic Nerve Atrophy in Methylmalonic Acidemia (MMA)
Laryssa Huryn1, Irini Manoli2, Elizabeth Harrington2, Jennifer
Sloan2, Brian P. Brooks1, Charles Venditti2, Wadih M. Zein1. 1National
Eye Institute, Bethesda, MD; 2National Human Genome Research
Institute, Bethesda, MD.
Purpose: To investigate the topographic pattern of retinal nerve fiber
layer thickness (RNFL) of patients with isolated MMA caused by
methylmalonyl-CoA mutase deficiency using spectral domain optical
coherence tomography (SD-OCT).
Methods: Twenty- three patients with isolated MMA (15 mut, 5
cblB and 3 cblA deficiency) admitted through a dedicated natural
history protocol at the National Institutes of Health (NCT00078078)
underwent comprehensive ophthalmic evaluations. Visual acuity,
color vision and Cirrus optical coherence tomography (Carl Zeiss
Meditec, Inc) data was analyzed. For patients under 18 years of age,
normative data published in the literature was used. Two patients
were removed from the analysis because of lack of adequate OCT
scans due to age and reduced cooperation.
Results: Age at presentation for ophthalmic examination ranged from
10 to 31 years (20.1y +/- 6.9y). Visual acuity at baseline examination
ranged from 20/12.5 to 20/800. Seventeen patients presented with at
least 20/25 visual acuity in one eye; of these, seven had demonstrable
RNFL thinning. Of the eighteen patients that had documented color
vision examinations at presentation, only two had abnormal results;
one of these patients presented with 20/25 visual acuity. Two patients
developed significant vision loss and optic atrophy with thinning of
the superior and inferior portions of the optic nerve. Of the patients
with optic nerve atrophy and no vision loss, the superior and inferior
quadrants of the optic nerve were most often involved.
Conclusions: Optic nerve atrophy is a well-known feature of
mitochondrial disease. Many mechanisms for the pathogenesis
of mitochondrial optic neuropathy have been proposed including
bioenergetic failure, oxidative stress and glutamate toxicity. The
atrophy in MMA patients presents primarily in the superior and
inferior quadrants of the optic nerve as measured by OCT which
differs from other optic neuropathies. It is recommended that
patients undergo regular eye examinations, including OCT to
monitor for changes in retinal nerve fibers. Future studies with
OCT measurements may help shed light on changes that occur over
time as well as highlight the earliest signs of change and a potential
therapeutic window in this disease process.
Commercial Relationships: Laryssa Huryn, None; Irini Manoli,
None; Elizabeth Harrington, None; Jennifer Sloan, None; Brian P.
Brooks, None; Charles Venditti, None; Wadih M. Zein, None
Support: NIH Intramural Research Program
Clinical Trial: NCT00078078
Program Number: 5555 Poster Board Number: B0126
Presentation Time: 8:30 AM–10:15 AM
Optic nerve morphology as a marker for disease severity in
cerebral palsy of perinatal origin
Deepta Ghate1, Veda Vedanarayanan2, James Corbett2, Abdulbaset
Kamour3, Sachin Kedar1. 1Ophthalmology, Truhlsen Eye Center,
University of Nebraska Medical Center, Omaha, NE; 2Neurology,
university of Mississippi Medical Center, Jackson, MS; 3University
of Kentucky, Lexington, KY.
Purpose: It has been hypothesized that a large cup in premature
children is associated with period of gestation (POG) > 28 weeks.
Early prognostication in children with POSE will result in early
rehabilitation with improved functional outcomes. Recognition of
the association of POSE and large cups will prevent unnecessary
examinations under anethesia for glaucoma.Our study aims to
correlate optic nerve head (ONH) pallor and cupping to period of
gestation (POG) at birth and severity of neurological damage in
children with perinatal onset static encephalopathy (POSE).
Methods: 54 consecutive patients with POSE were enrolled.
Exclusion criteria included genetic, metabolic or congenital
structural brain abnormalities not related to perinatal complications;
intraocular disease (ROP/glaucoma/cataract) and hydrocephalus.
ONH morphology (pallor and cup to disc ratio-CDR) was assessed
independently by 2 fellowship-trained ophthalmologists by dilated
examination using direct and indirect ophthalmoscopy. ONH
were labeled as pale or large cup (cup/disc ratio≥0.5) only if the
2 ophthalmologists agreed. Inter-rater reliability was >0.8 for all
parameters . A pediatric neurologist determined eligibility, age
of onset of POSE, neurological deficit and reviewed available
neuroimaging.
Results: Mean age was 11.88±6.53years; period of gestation at birth:
33.26±4.78weeks. 33/54 (61%) showed ONH pallor or cupping. Of
17 patients with ONH pallor, 88% were quadriplegic and 82% nonambulatory. Mean cup/disc ratio was 0.45±0.22; 50% patients had
large cup. Multivariate logistic regression models showed that disc
pallor was significantly associated with non-ambulatory status (OR:
12.5; p=0.03) and quadriplegia (OR: 21.7; p=0.0025) and large cup
was associated with age at examination (OR 1.15; p=0.025). Cup/disc
ratio and age showed positive correlation (r=0.42; p=0.002). ONH
parameters were not statistically associated with POG at birth.
Conclusions: ONH changes are common in POSE and are not
associated with POG. Optic disc pallor, a bedside clinical finding
is a prognostic indicator for severe neurological insult in high-risk
children with perinatal complications that should prompt early
referral for rehabilitation. Optic disc cupping is correlated with the
age at examination which may indicate that the cupping worsens with
age.
Commercial Relationships: Deepta Ghate, None; Veda
Vedanarayanan, None; James Corbett, None; Abdulbaset
Kamour, None; Sachin Kedar, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 5556 Poster Board Number: B0127
Presentation Time: 8:30 AM–10:15 AM
The Site of Inflammation in the Artery Wall in Temporal Arteritis
Angeline Wang, Krishna Surapaneni, Daniel M. Albert.
Ophthalmology and Visual Sciences, University of Wisconsin,
Madison, WI.
Purpose: Temporal arteritis is an ophthalmic emergency and requires
prompt treatment to prevent vision loss. The gold standard for
diagnosis is the temporal artery biopsy. Current literature describes
a positive biopsy as revealing chronic granulomatous inflammation
at the level of the internal elastic lamina. The purpose of this study
was to verify the location of most severe inflammation within a
positive temporal artery and study other characteristics of our series
in comparison to previous reports.
Methods: The list of patients with biopsy-proven temporal arteritis
was generated by searching the University of Wisconsin Eye
Pathology Laboratory database for the terms “giant cell arteritis” and
“temporal arteritis.” Charts and pathology slides for patients from the
last 15 years (1999 to present) were reviewed (n = 32). Cases with
indeterminate diagnoses were excluded, as were cases where clinical
information was unavailable.
Results: The average age of onset was 76.2 years, with 81% (26/32)
of positive cases diagnosed in women. Patients were treated with
oral steroids for an average of 4.25 days prior to biopsy. Unilateral
temporal artery biopsies were submitted in 91% of cases (29/32);
the remaining biopsies were bilateral. Both arteries were positive in
two of the bilateral cases; one was positive and the other negative
in the third case. The average artery sample length was 20 mm.
Histopathologic features of the positive biopsies included intimal
hyperplasia (32/32), lymphocytes (32/32), epithelioid cells (32/32),
giant cells (29/32), fragmented internal elastic lamina (29/32), lumen
narrowing (18/32), and concomitant Monckeberg’s arteriosclerosis
(15/32). Skip areas were noted in 9% (3/32) of cases. The most severe
inflammation was at the level of the media and adventitia in 37%
of biopsies (12/32); the remaining had full thickness inflammation.
No biopsies had inflammation isolated at or centered on the internal
elastic lamina.
Conclusions: In contrast to the current literature, biopsies of
patients with temporal arteritis reveal the principal focus of chronic
granulomatous inflammation to be at the level of the media and
adventitia or throughout the layers of the artery, not at the level of
the internal elastic lamina. Other findings are generally consistent
with previous reported series. Our findings lead us to hypothesize
that the muscularis and adventitia may play an inciting role in the
pathogenesis of temporal arteritis.
Commercial Relationships: Angeline Wang, None; Krishna
Surapaneni, None; Daniel M. Albert, None
Support: Department of Ophthalmology and Visual Sciences CORE
Grant (UW – Madison); Financial Support from Ocular Services on
Demand (OSOD)
Program Number: 5557 Poster Board Number: B0128
Presentation Time: 8:30 AM–10:15 AM
Final Diagnosis in Headache Patients Following Temporal Artery
Biopsy
Marie Somogyi, Sarah Hale, David K. Yoo, Yasmin Shayesteh.
Ophthalmology, Loyola University Medical Center, Maywood, IL.
Purpose: Giant cell arteritis (GCA) is a diagnosis made based on
a combination of signs, symptoms and laboratory evidence (1).
Temporal artery biopsy is the gold standard for the diagnosis of
GCA and a referral for biopsy is commonly encountered entity
in oculoplastic surgery practice (2). Our review investigates the
final diagnosis and clinical course of headache patients undergoing
temporal artery biopsy with the suspicion of giant cell arteritis
(GCA). To our knowledge, this series of 143 patients is the largest
study to date evaluating the final diagnosis in temporal artery biopsy
patients from a single institution.
Methods: Retrospective chart review of 143 patients who underwent
a temporal artery biopsy from January 2006 to April 2014 by vascular
surgery, plastic surgery and oculoplastic surgery at our institution.
Results: Of 143 patients, 15 had positive biopsies (10.5%) and 128
had negative biopsies. Among the patients with negative biopsies,
41 patients (28.7%) ultimately were given the diagnosis of a benign
headache. Biopsy-negative GCA was diagnosed when the American
College of Rheumatology classification (7) criteria were met,
symptoms improved within 3 days of corticosteroid therapy and
no other diagnosis relevant to the patient’s presenting symptoms
was diagnosed. 30 patients (20.9%) were ultimately diagnosed
with biopsy-negative GCA. Of the remaining negative biopsies,
7 (4.9%) were found to have non-arteritic anterior ischemic optic
neuropathy, 3 (2.1%) had isolated polymyalgia rheumatic, 3 (2.1%)
with systemic vasculitis, 3 (2.1%) with acute angle closure, 3 (2.1%)
with hypertensive urgency, 2 (1.4%) with posterior ischemic optic
neuropathy, and 2 (1.4%) with granulomatosis with polyangiitis.
Conclusions: Even though only 15 patients (10.5%) had positive
temporal artery biopsies, a total of 45 patients (31.5%) were
ultimately treated for giant cell arteritis. Although the majority of
patients (41 patients or 28.7%) undergoing temporal artery biopsy
were diagnosed with benign headache, it is important to consider
other vision and life threatening entities when presented with a
patient with suspected GCA.
Final Diagnoses Following Temporal Artery Biopsy
Commercial Relationships: Marie Somogyi, None; Sarah Hale,
None; David K. Yoo, None; Yasmin Shayesteh, None
Program Number: 5558 Poster Board Number: B0129
Presentation Time: 8:30 AM–10:15 AM
Acute ischemic stroke in monocular vision loss of vascular
etiology
Lucy Zhang1, Richard Kim3, Danielle Rudich4, Robert Lesser1, 2,
David Greer2, Hardik Amin2. 1Ophthalmology and Visual Sciences,
Yale University, New Haven, CT; 2Neurology, Yale University, New
Haven, CT; 3Yale University School of Medicine, New Haven, CT;
4
The Eye Care Group, New Haven, CT.
Purpose: To evaluate the rate of co-occurrence of acute ischemic
stroke and monocular vision loss of vascular etiology, as diagnosed
by magnetic resonance imaging (MRI) with diffusion-weighted
imaging (DWI). Two recent retrospective studies have shown that
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
patients with monocular vision loss of ischemic origin are also more
likely to have acute brain infarcts; however, these studies did not
exclude patients with concurrent focal neurologic deficits (totaling
13-15% of their study populations). The goal of our study is to
evaluate the likelihood of subclinical acute stroke identified on DWI
in patients presenting with isolated monocular vision loss.
Methods: A retrospective analysis was performed using medical
records from February 2013 through August 2014 at Yale-New Haven
Hospital of patients who were diagnosed with monocular vision loss.
Patients whose vision loss was likely related to a vascular etiology
(such as amaurosis fugax or central or branch retinal vascular
occlusion) and who underwent brain MRI within a seven day period
were included. We determined the proportion of patients with
monocular vision loss and acute stroke on brain MRI.
Results: A total of 448 records were reviewed. Of these, 293 patients
had monocular vision loss of suspected or confirmed vascular
etiology. Seventy-four patients were excluded due to the presence
of other focal neurologic symptoms. Of the remaining 219 patients,
54 underwent MRI of the brain within seven days of the onset of
symptoms, and 13 (24%) were found to have evidence of acute
ischemic stroke based on restricted diffusion.
Conclusions: Patients with monocular vision loss due to amaurosis
fugax, CRAO, or BRAO may have up to 24% risk of ischemic stroke
as a result of thromboembolic phenomena. This study provides
further evidence that ophthalmologists should refer monocular vision
loss patients for neurologic evaluation and brain MRI with DWI even
when vision loss is the isolated symptom.
Commercial Relationships: Lucy Zhang, None; Richard Kim,
None; Danielle Rudich, None; Robert Lesser, None; David Greer,
None; Hardik Amin, None
Program Number: 5559 Poster Board Number: B0130
Presentation Time: 8:30 AM–10:15 AM
Chiasmal syndrome: clinical features in mexican patients, a 5
year review
Aline Astorga-Carballo, Juan Carlos Serna-Ojeda, Mayra F.
Camargo. Instituto de Oftalmologia Fundación Conde de Valencia
I.A.P., Mexico City, Mexico.
Purpose: To evaluate the ocular manifestations of intracranial
pathology producing a chiasmal syndrome, for those initially
diagnosed or referred to an ophthalmologic institution.
Methods: An observational and retrospective study was performed
with review of the records of all the patients with a diagnosis of
chiasmal syndrome at an ophthalmologic reference center in a 5-year
period. The variables analyzed included: demographic data, reason
for consultation, visual acuity, visual field defect in Goldmann’s
perimetry, afferent pupillary defect, changes in the color vision test,
characteristics of the optic nerve and cranial imaging.
Results: 104 patients were included with a median age of 52 years
(range 4 – 86 years). 54 patients (51.9%) were initially diagnosed
because of the ophthalmologic examination, and 50 (48.07%) were
referred with the presumptive diagnosis of an intracranial tumor.
The median visual acuity at the time of diagnosis was 20/60 in the
eye with worst vision, with 41 patients with a vision in one eye
severely affected (worst than 20/400). The main symptoms were
decreased central vision in 57 patients (54.8%) and changes in the
peripheral visual field in 20 (19.2%); other aggregated manifestations
like headache and systemic signs for elevated pituitary hormones
were present in 10 (9.61%) and 18 cases (17.3%) respectively. Nine
patients had a misdiagnosis of glaucoma for years. The most common
visual field defect was bitemporal hemianopsia in 59 (56.73%). 54
patients (51.92%) had relative afferent pupillary defect, and in 65
(62.5%) the color vision test was affected. The optic nerve presented
changes in 64.4% of the population. Cranial imaging confirmed the
presence of an intracranial tumor in 23 cases (22.11%), being the
most common pathology a pituitary adenoma.
Conclusions: Ophthalmologic examination could imply the initial
diagnosis of intracranial pathology as the ocular manifestations are
varied. Decreased vision is a common reason for consultation in
patients with chiasmal syndrome, and other neurologic and systemic
findings can be present. Complimentary study findings of intracranial
pathology include bitemporal hemianopsia in Goldmann’s perimetry,
altered color vision test and diagnostic cranial imaging.
Commercial Relationships: Aline Astorga-Carballo, None; Juan
Carlos Serna-Ojeda, None; Mayra F. Camargo, None
Program Number: 5560 Poster Board Number: B0131
Presentation Time: 8:30 AM–10:15 AM
Proposing a new mechanism for chiasmal visual field loss in an
unusual case of junctional scotoma: the degree of stretch of the
anterior optic chiasm closely relates to the pattern of visual loss
in a patient
Yevgeniy Sychev, Raghu C. Mudumbai. University of Washington,
Seattle, WA.
Purpose: To report a case of an unusual junctional scotoma in a
patient produced via a stretching of an anterior aspect of the optic
chiasm.
Methods: A single case report describing a patient with an unusual
mechanism of junctional scotoma is presented.
Results: We present a case of an unusual junctional scotoma
resulting from compression of the anterior optic chiasm by a pituitary
macroadenoma. A patient presented complaining of unilateral vision
loss in the left eye. Automated Humphrey visual field demonstrated
dense temporal hemianopia in the left eye and only trace visual field
change in the left eye. Magnetic Resonance Imaging demonstrated
a macroadenoma under the anterior aspect of the optic chiasm
resulting in marked stretch of the chiasm in the horizontal coronal
axis. Following surgical decompression the visual field deficit has
resolved. (see figure) Postoperative imaging demonstrated marked
reduction in the degree of chiasm stretch.
Conclusions: The visual field deficit observed in the presented case
cannot be explained by the classic theory that states that dysfunction
of visual axons stems from their compression at the chiasm. The
deficit observed is neither a bitemporal hemianopia, nor a typical
junctional scotoma seen in syndromes of the middle and anterior
chiasm compression respectively. Instead, the presented visual field
defect implies involvement of predominantly the nasal fibers of the
left optic nerve with sparing of the left temporal fibers and the right
optic nerve. Pure compressive forces on the chiasm does not easily
explain this pattern of visual loss. Close correlation between the
degree of chiasm stretch and development of the temporal scotoma
in this patient suggests that stretch of nerve fibers likely played an
important role. The perpendicular relationship of the uncrossed fibers
of the left optic nerve to the tumor with minimum lateral stretch
forces at the chiasm may have lead to their relative protection. The
crossing fibers may have been injured because of their partially
parallel course to the horizontal stress forces in the anterior chiasm
from the tumor. This mechanism of optic neurologic dysfunction
may also be important contributor in other cases of bitemporal and
junctional scotomas.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
529 Visual pathways
Thursday, May 07, 2015 12:00 PM–1:45 PM
4CD Mile High Blrm Paper Session
Program #/Board # Range: 5855–5861
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Commercial Relationships: Yevgeniy Sychev, None; Raghu C.
Mudumbai, None
Program Number: 5855
Presentation Time: 12:00 PM–12:15 PM
Retinal Development in Achromatopsia: A Prospective Study
of Infants and Young Children using Optical Coherence
Tomography
Helena Lee1, Ravi Purohit1, Viral Sheth1, Rebecca J. McLean1, Gail
Maconachie1, Susanne Kohl2, Bart P. Leroy3, 4, Michel Michaelides5,
Frank A. Proudlock1, Irene Gottlob1. 1Ophthalmology, University
of Leicester, Leicester, United Kingdom; 2Insitute for Ophthalmic
Research, Molecular Genetics Laboratory, Universitätsklinikum
Tübingen, Tübingen, Germany; 3Dept of Ophthalmology & Ctr
for Medical Genetics, Ghent University, Ghent, Belgium; 4Div of
Ophthalmology & Ctr for Cellular & Molecular Therapeutics, The
Children’s Hospital of Philadelphia, Philadelphia, PA; 5UCL Institute
of Ophthalmology, London, United Kingdom.
Purpose: To characterize postnatal retinal development in infants and
young children with achromatopsia using hand-held spectral domain
optical coherence tomography (HH-SDOCT) and to investigate
whether retinal changes are progressive.
Methods: Forty-one mixed cross-sectional and longitudinal HHSDOCT images were obtained from eight infants and young children
with achromatopsia (mean age 3.3 years; range 0-8.3 years) and
compared with 82 age-matched control examinations. All patients
had homozygous mutations in either CNGA3 (n=2) or CNGB3 (n=6).
Retinal layer segmentation was performed manually using ImageJ.
Differences in development of retinal layers with age between the
achromatopsia and control groups were analysed using linear mixed
regression modelling. The severity and progression of photoreceptor
disruption was evaluated in all participants with longitudinal data
(11 eyes of 6 participants; mean follow-up time 14.8 months; range
7.2-20.9 months).
Results: In achromatopsia, retinal thickness increased more slowly
with age and was reduced at the fovea in comparison to controls
(p < 0.05). There was delayed regression of the inner retinal layers
(IRLs) at the fovea and a reduction in the thickness of the perifoveal
IRLs. This was especially significant for the perifoveal inner (p <
0.0001) and outer (p < 0.01) plexiform layers. Elongation of the outer
retinal layers (ORLs) was diminished across the retina resulting in
a significant reduction in ORL thickness, especially at the fovea (p
< 0.0001). There was evidence of an increase (4 eyes), decrease (1
eye) and no change (2 eyes) in the grade of photoreceptor disruption
on longitudinal assessment. Interestingly, in 4 eyes both an increase
and decrease in the grade of photoreceptor disruption was observed at
different time points.
Conclusions: Previously, it has been thought that retinal development
is arrested in achromatopsia. We demonstrate ongoing retinal
development in achromatopsia in the postnatal period albeit at an
altered rate and magnitude in comparison to controls. Achromatopsia
appears to be a dynamic and progressive condition in infants and
young children. This has potential implications for planned gene
therapy, since intervention at the earliest stages of the disease may
promote normal retinal development.
Commercial Relationships: Helena Lee, None; Ravi Purohit,
None; Viral Sheth, None; Rebecca J. McLean, None; Gail
Maconachie, None; Susanne Kohl, None; Bart P. Leroy, None;
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Michel Michaelides, None; Frank A. Proudlock, None; Irene
Gottlob, None
Support: Medical Research Council, London, UK (grant number:
MR/J004189/1), Ulverscroft Foundation, Leicester, UK and
Nystagmus Network UK.
Program Number: 5856
Presentation Time: 12:15 PM–12:30 PM
Optical Coherence Tomography Findings in Huntington’s
Disease: a Potential Biomarker of Disease Progression?
Hannah M. Kersten1, Helen V. Danesh-Meyer1, Dean H. Kilfoyle2, 3,
Richard H. Roxburgh2, 3. 1Department of Ophthalmology, University
of Auckland, Auckland, New Zealand; 2Department of Neurology,
Auckland City Hospital, Auckland, New Zealand; 3Centre for Brain
Research, University of Auckland, Auckland, New Zealand.
Purpose: Previous reports of ocular abnormalities in Huntington’s
disease (HD) have detailed eye movement disorders. Mitochondrial
dysfunction is a feature of HD, and diseases affecting mitochondrial
function frequently manifest neuro-ophthalmic signs and symptoms
including optic neuropathy. However, these changes have not been
reported in HD. The objective of this case-control study was to
investigate optic nerve and macular morphology in HD using optical
coherence tomography.
Methods: A total of 26 HD patients and 29 controls underwent a
thorough neuro-ophthalmic examination including digital retinal
photography and spectral domain optical coherence tomography
(OCT) scans of the macula and peripapillary retinal nerve fibre layer
(RNFL). Genetic testing results, disease duration, HD disease burden
scores and unified HD rating scale (UHDRS) motor scores were
acquired for HD patients.
Results: Of the 26 patients with HD, 13 were women; the mean
age was 52.0 years (range 33 – 68). The control group was matched
for age and gender. The range of the CAG repeat expansion size
was 38-48 repeats. Amongst the 52 HD patient eyes, eight were
excluded from macular and/or RNFL analysis due to poor scan
quality. After statistical analysis confirmed no significant difference
in the measurements from both eyes of each participant, 22 right
eyes were included in OCT analysis. Temporal RNFL thickness
was significantly reduced in the HD group (62.3 (± 7.3) μm vs. 69.8
(±10.8) μm, p = 0.005). There was no significant difference in total
macular volume between HD patients and controls (8.57 (± 0.38) mm
vs. 8.62 (±0. 31) mm), p = 0.63). There was, however, a significant
negative (p < 0.05) correlation between macular volume and UHDRS
motor scores (R2 = -0.56), and disease duration (R2 = -0.57).
Conclusions: The temporal RNFL is preferentially thinned in HD
patients. This could implicate mitochondrial dysfunction as the
temporal RNFL is reduced in other conditions where mitochondrial
function is impaired, including Leber’s hereditary optic neuropathy.
The correlation between the decrease in macular volume and
increasing motor disability suggests that ocular coherence
tomography may be a useful biomarker for disease progression in
HD. Larger, longitudinal studies are required in order to corroborate
these findings.
Commercial Relationships: Hannah M. Kersten, None; Helen
V. Danesh-Meyer, None; Dean H. Kilfoyle, None; Richard H.
Roxburgh, None
Program Number: 5857
Presentation Time: 12:30 PM–12:45 PM
Very Preterm Neonatal Retinal Nerve Fiber Layer Thickness is a
Biomarker of Brain Anatomy and Neurodevelopmental Health
Adam Rothman1, Monica B. Sevilla1, Mays El-Dairi1, 3, Joshua
Shimony4, Kathyrn Gustafson3, Carolyn Pizoli3, Amy Tong1, Sina
Farsiu2, 1, Sharon Freedman1, 3, Cynthia A. Toth1, 2. 1Ophthalmology,
Duke University School of Medicine, Durham, NC; 2Biomedical
Engineering, Duke University Pratt School of Engineering, Durham,
NC; 3Pediatrics, Duke University School of Medicine, Durham, NC;
4
Radiology, Washington University of St. Louis School of Medicine,
St. Louis, MO.
Purpose: To assess retinal nerve fiber layer (RNFL) thickness
measurements at term equivalent age (TEA, 37-42 weeks
postmenstrual age, PMA) in very preterm (VPT, <32 weeks
gestational age) infants and to compare these measurements to
maturity, brain magnetic resonance imaging (MRI) findings, and
neurodevelopment.
Methods: In a prospective cohort study, VPT infants and full
term controls were imaged with handheld spectral domain optical
coherence tomography (Bioptigen, Inc., Research Triangle Park, NC)
in the nursery. A custom MATLAB script (Mathworks, Inc., Natick,
MA) segmented the RNFL, and graders corrected segmentation and
marked the fovea and optic nerve center. From these coordinates,
a second script created an organizing fovea-optic nerve axis and
calculated mean RNFL thickness for the papillomacular bundle
(PMB), extending from -15° to +15° to the organizing axis, at a radial
distance of 1.5 mm from the optic nerve center. For VPT infants,
clinical brain MRI scans obtained in the nursery were scored for
structural abnormalities based on scaling of Kidokoro et al. (Am J
Neuroradiol, 2013, 2208-14). In addition, Bayley Scales of Infant and
Toddler Development were assessed at 18-24 months corrected age,
by evaluating cognitive, language, and motor skills. Expert MRI and
Bayley evaluators were masked to eye imaging data. We assessed the
relationships between mean RNFL thickness and Bayley scores or
MRI scores using linear regression.
Results: Mean ± standard deviation RNFL thickness at the PMB was
greater for term (n=50, 72 ± 13 μm) versus VPT infants (n=57, 61
± 17 μm, P<0.001), respectively. Retinal nerve fiber layer thickness
inversely correlated with MRI scores while in the nursery (signifying
more extensive global lesions (n=14, R2=0.37, P=0.02)) as well as
cognitive (n=29, R2=0.19, P=0.015) and motor scores (R2=0.21,
P=0.009) at 18-24 months follow-up. Retinal nerve fiber layer
thickness did not correlate with language scores (P=0.67).
Conclusions: Thinner RNFL at the PMB in TEA VPT infants
correlates with worse cognitive and motor skills at 18-24 months
corrected age and with worse abnormalities on brain MRI. Retinal
nerve fiber layer thickness measured at the infant bedside provides
insight into VPT infants’ brain and neurodevelopment.
Commercial Relationships: Adam Rothman, None; Monica B.
Sevilla, None; Mays El-Dairi, None; Joshua Shimony, None;
Kathyrn Gustafson, None; Carolyn Pizoli, None; Amy Tong,
None; Sina Farsiu, Duke University (P); Sharon Freedman,
None; Cynthia A. Toth, Alcon (F), Bioptigen (F), Duke University
(unlicensed) (P), Genentech (F), National Institute of Health (F),
Research to Prevent Blindness (F), Retina Research Foundation (F),
The Andrew Family Foundation (F), The Hartwell Foundation (F)
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Program Number: 5858
Presentation Time: 12:45 PM–1:00 PM
NAION: Analysis of the cellular immune response and treatment
targeting
Steven L. Bernstein1, 2, Yan Guo1, Valerie Touitou3, Zara Mehrabyan1.
1
Ophthalmology, Univ of Maryland Sch of Medicine, Baltimore, MD;
2
University of Maryland, Anatomy and Neurobiology, Baltimore,
MD; 3Neuro-Ophtalmologie, hopital salpetrie, Paris, France.
Purpose: We recently demonstrated that optic nerve lesion in clinical
specimens and in both the primate (pNAION) and rodent (rAION)
NAION models generates a strong, stereotypical cellular immune
response that extends over days and weeks (Salgado and Vilson,
2012; Zhang et al 2008). Cellular macrophage responses can be either
M1 (classical neurodegenerative) or M2 (alternative-neuroprotective).
We wanted to use the rAION model to: 1) Evaluate the specific
M-type response in the primary and secondary optic nerve damage
regions; 2) Determine whether we could switch the M-type response
by pharmacological means.
Methods: We utilized Sprague-Dawley male rats and induced rAION
in one eye; the second eye was left as a control. Animals were treated
post-induction with either vehicle, minocycline (30mg/kg/IP/day, or
administered an intraventricular dose of IL4+TGFβ. Tissues were
collected from the lamina and distal ON at a variety of times postinduction, and evaluated for M1 markers CD16/32 and iNOS, M2
markers Arginase-1 (Arg1) and Ym1, and microglia and universal
immune cell markers CD11b and Iba1.
Results: The primary ON lesion at the lamina in vehicle treated
animals exhibited a strong M1 response by 3 days and continued to at
least 7 days post-induction, with upregulation of M1 markers. . Early
and late analysis of the primary lesion in treated animals revealed
a only a modest M2 response, in the minocycline treatment group,
with continuing M1 expression. Interestingly, Arg-1 expression
was also seen. Although axons degenerate along the entire ON
with oligodendrocyte death, there was minimal M1 response in the
distal ON at either 7- or 30 days post-induction, in either vehicle or
minocycline-treated animals.
Conclusions: NAION likely induces a strong early (3-7d) M1
cellular response at the primary lesion, with minimal alteration of the
M1/M2 macrophage response in regions with only secondary axonal
degeneration. The lack of M2 response in animals given minocycline
after induction, compared with the reported neuroprotective response
in animals given minocycline prior to treatment (Fel et al, 2014), as
well as the reported post-induction neuroprotection in rodents and
primates using prostaglandin J2 suggests that minocycline may be
ineffective when given after ON damage has commenced.
Commercial Relationships: Steven L. Bernstein, None; Yan Guo,
None; Valerie Touitou, None; Zara Mehrabyan, None
Support: Supported by NEI RO1EY015304 to SLB
of the MR images to measure the displacement of the optic tract in
the pre-chiasmal, chiasmal, and post-chiasmal regions. They also
subjectively assessed the degree of right-left asymmetry in the tumor.
To quantify the degree and laterality of visual field loss, we utilized
algorithms previously developed for the Neurological Hemifield Test.
In brief, we used the pointwise pattern deviation values from each
visual field to assign a score proportional to the degree of vision loss
loss at each point. These pointwise scores were then summed in each
quadrant of the visual field. Each right-left pair of visual fields for
each patient was summarized in terms of temporal field asymmetry
(right temporal field minus left temporal field), the proportion of
visual field loss that was temporal, total field asymmetry (all right eye
minus all left eye), and total visual field damage (sum of all 4 fields
in both eyes). These visual field metrics were then compared to either
the maximum displacement of the optic tract or the tumor asymmetry
on MR imaging.
Results: Of the 114 subjects, 64 (56%) were male and the average
age was 54.6 years. Both the summation of vision loss in both eyes
and the proportion of visual field loss in the temporal hemifields
were statistically significantly related to the maximum displacement
of the optic tract (both p < 0.001 for fit of linear regression) - Figure
1. There was no statistical relationship between the subjective
assignment of tumor asymmetry on MR imaging and either the
asymmetry of temporal vision loss (R-L) or the asymmetry of total
vision loss (R-L) (p > 0.05 by analysis of variance) - Figure 2.
Conclusions: As might be expected, the displacement of the optic
tract by pituitary tumors is quantitatively associated with both the
total amount of vision loss and the proportion of visual field loss that
is temporal. Although there was right-left asymmetry of vision loss
in some subjects, it was not related to the subjective assessment of
asymmetry on MR imaging.
Program Number: 5859
Presentation Time: 1:00 PM–1:15 PM
Quantitative analysis of the size and asymmetry of pituitary
lesions and the associated visual field loss
Michael V. Boland1, In Ho Lee2, David M. Yousem2, Neil R. Miller1.
1
Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD;
2
Department of Radiology and Radiological Sciences, Johns Hopkins
University, Baltimore, MD.
Purpose: To understand the quantitative relationship between the
size and asymmetry of pituitary tumors and the visual field loss they
cause.
Methods: We identified patients who had magnetic resonance
(MR) imaging with a diagnosis of pituitary macroadenoma who
also had reliable visual field testing. Neuroradiologists reviewed all
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
Relationship between asymmetry of visual field damage and of the
tumor on MR imaging.
Commercial Relationships: Michael V. Boland, None; In Ho Lee,
None; David M. Yousem, None; Neil R. Miller, None
Support: NIH Grant EY01765
Program Number: 5860
Presentation Time: 1:15 PM–1:30 PM
Prediction of visual field defects in children with perinatal
arterial ischemic stroke using early DTI-based tractography of
the optic radiation
Yvonne Koenraads, Giorgio L. Porro, Kees P. Braun, Floris
Groenendaal, Linda S. de Vries, Niek E. van der Aa. University
Medical Center Utrecht, Utrecht, Netherlands.
Purpose: Visual field (VF) defects are a common sequela of perinatal
arterial ischemic stroke (PAIS) and can be detected using specialized
VF assessments, such as the ‘behavioral visual field screening’ test
(BEFIE). Conventional MRI does not always predict VF deficits. The
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
aim of this study was to investigate whether diffusion tensor imaging
(DTI) based tractography of the optic radiation (OR) at 3 months of
age improves the prediction of VF defects.
Methods: Seventeen patients with unilateral PAIS, who underwent
conventional MRI (T1/T2) and DTI at the age of 3 months and a
BEFIE VF examination later in life (median age 3yrs) were included.
DTI-based tractography of the bilateral OR was performed, and the
average fractional anisotropy (FA), axial (λ1), radial (λ23) and mean
diffusion (MD) were extracted. Asymmetry of these parameters was
used as a predictor of VF defects in the 15 patients with a conclusive
result of the BEFIE test, using receiver operating characteristic
(ROC) analysis. Conventional MRI was used to assess myelination
of both ORs and scored as symmetrical, mildly asymmetrical or
severely asymmetrical and compared with the VF results.
Results: Nine children had a normal VF, 6 children had a VF
defect (5 hemianopia and 1 quadrantanopia) and 2 children had an
inconclusive result of the BEFIE tests. ROC curve analysis revealed
that VF outcome could be correctly predicted based on conventional
MRI assessment in the majority of children, with an area under the
curve (AUC) of 0.94 (95%CI 0.70-1.00). Prediction based on DTI
parameter asymmetry indices showed an AUC of 0.98 (95%CI 0.751.00), 0.85 (95%CI 0.58-0.98), 0.96 (95%CI 0.72-1.00) and 0.94
(95%CI 0.70-1.00) for FA, λ1, λ23 and MD, respectively (see Figure 1
& Table 1).
Both children who were excluded from the analysis since they had
inconclusive BEFIE test results also had an inconclusive prediction
of the VF according to the cut-off values of de DTI parameters based
on the other 15 children.
Conclusions: Asymmetry in myelination of the OR at 3 months and
especially DTI-based tractography of the OR can be used to predict
VF defects after PAIS.
Figure 1. DTI parameter asymmetry indices of children with and
without a visual field defect
Table 1. Results of diagnostic values of DTI parameter asymmetry
indices to predict visual field (VF) defects
Commercial Relationships: Yvonne Koenraads, None; Giorgio
L. Porro, None; Kees P. Braun, None; Floris Groenendaal, None;
Linda S. de Vries, None; Niek E. van der Aa, None
Support: ODAS Foundation, Dr. F.P. Fischer Foundation, SNOO
Foundation, Rotterdamse Blindenbelangen Foundation and Vrienden
van het UMCU Foundation
Program Number: 5861
Presentation Time: 1:30 PM–1:45 PM
Long Distance Homonymous Hemi-Macular Retrograde
Degeneration of the Visual Pathway: A Comparison of Anterior
and Posterior Visual Pathway Lesions
Alekya Rajanala, M Ali Shariati, Yaping J. Liao. Stanford School of
Medicine, Palo Alto, CA.
Purpose: Trans-synaptic degeneration of the visual pathway
following ablation of the striate cortex is well established in nonhuman primates and involves parvocellular retino-geniculate
connections. In humans, trans-synaptic degeneration is more
controversial but has been described recently. In this study, we used
optical coherence tomography (OCT) to examine the severity and
timing of retrograde degeneration in human visual pathway lesions.
Methods: We performed a retrospective chart review of patients
with homonymous visual field loss and confirm lesions of the visual
pathway on brain imaging studies. Patients were categorized by
location of brain lesion. We analyzed over 70 high quality OCT
studies and correlated the findings with visual field loss and MRI.
Results: We studied the changes in macular ganglion cell complex
in 15 patients with anterior and 20 patients with posterior visual
pathway lesions. There was significant hemi-macular thinning of
the ganglion cell complex (GCL+IPL) in patients with anterior
(abnormal: 56.2±2.5 mm, normal: 78.2±1.5 mm, N=15, P<0.0001)
and posterior (abnormal: 63.6±2.3 mm, normal: 71.7±2.6 mm, N=19,
P=0.01, Mann-Whitney). At one year after onset, anterior lesions
led to significantly more severe GCC thinning than posterior lesions
(anterior: 59.2±2.9 mm, N=10; posterior: 67.8±2.8 mm, N=6; P=0.03).
At two years after onset, the rate of thinning of the anterior lesions
was significantly faster and more than three times that of the posterior
lesions (anterior: 4.6±1.0 mm/month, posterior: 1.2±1.1 mm/month;
P=0.05). Patients with congenital or incidentally noted homonymous
hemifield defects often exhibited significant hemi-macular thinning,
presumably because the thinning has had years to develop.
Correlation between the pattern of retinal thinning and that of visual
field loss indicated that a decrease of 1 dB in visual field sensitivity
predicts a decrease of 0.1543 mm in GCC thickness.
Conclusions: Retrograde, homonymous, hemi-macular thinning
occurred in the human visual pathway over long distance, even
trans-synaptically. There was more rapid and more severe thinning
in anterior visual pathway lesions (optic tract, LGN) compared with
that of occipital lobe lesions. Further investigation of trans-synaptic
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts by Scientific Section/Group - Eye Movements / Strabismus / Amblyopia / Neuro-Ophthalmology
degeneration can assist regeneration therapy and efforts to restore
patient vision.
Commercial Relationships: Alekya Rajanala, None; M Ali
Shariati, None; Yaping J. Liao, None
Support: Career Award in Biomedical Sciences, Center for
Biomedical Imaging at Stanford, Weston Havens Foundation,
Stanford Vice Provost for Undergraduate Research, Stanford
Undergraduate Major Grant
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].