Download Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session

Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706
127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY
646 - D686
The Microrna Expression Profile of Rodent Extraocular Muscles
647 - D687
Quasi-linear Viscoelastic Behavior of Bovine Extra-ocular Muscles
C.A. McMullen, F.H. Andrade. Physiology, University of Kentucky, Lexington, KY.
L.H. Yoo1A,2, H. Kim1A, V. Gupta1B,1A, J.L. Demer2,1B. AMechanical Engineering,
B
Biomedical Engineering, 1UCLA, Los Angeles, CA; 2Ophthalmology, UCLA, Jules
Stein Eye Inst/Los Angeles, CA.
Purpose: The extraocular muscles (EOMs) represent an extreme example of skeletal
muscle specialization. It is not surprising that transcriptional and biochemical studies
of these muscles have identified many genes and proteins differentially expressed in
EOMs compared to limb skeletal muscles. MicroRNAs (miRNAs) are small noncoding
RNAs (21 to 26 nucleotides) that regulate gene expression by inhibiting mRNA
translation or promoting mRNA degradation. Some miRNAs are tissue-specific and
may influence the adult tissue phenotype. In this study, we tested the hypothesis
that EOMs would have a unique miRNA expression profile that would include a
combination of muscle-specific miRNAs.
Methods: We isolated EOMs and gastrocnemius muscles from adult male SpragueDawley rats for expression profiling using miRNA microarrays, real-time quantitative
PCR, and northern blots.
Results: A total of 223 miRNAs were present in all muscle samples (out of 636 miRNAs).
Fourteen miRNAs were more abundant in EOMs compared to gastrocnemius, and five
were less abundant. Surprisingly, miR-206, previously demonstrated to be enriched in
skeletal muscle, was significantly less abundant in EOM. miRNAs more abundant in
EOM were miR-133a/b which have been found in skeletal muscle and heart. miRNAs
found in brain were also increased in EOM: miR-24 and miR-30c. Ubiquitously
expressed miRNAs, miR-143and and miR-320 were also upregulated in EOM.
Conclusions: The results support our initial hypothesis that EOMs have a specific
miRNA expression profile, significantly different from that of a limb skeletal muscle.
These EOM-enriched miRNAs may represent a hitherto unrecognized regulatory
influence on the phenotype of these muscles.
Supported by NEI EY12998
CR: C.A. McMullen, None; F.H. Andrade, None.
Support: NEI EY12998
648 - D688
Identification of the Unique Extraocular Muscle (EOM) ‘microRNAome’
Purpose: There has been no prior comprehensive analytical model of the nonlinear
viscoelastic stress-strain behavior of extraocular muscles (EOMs). The present study
describes the nonlinear, history-dependent viscoelastic properties and elastic stressstrain relationship of the EOMs using a quasi-linear viscoelastic (QLV) model.
Methods: From each of the six oculorotary EOMs obtained fresh from a local abattoir,
longitudinally oriented specimens were taken from different regions and subjected
to uniaxial tensile, relaxation, and cyclic loading testing using an automated load
cell under temperature and humidity control. Twelve samples were subjected to
uniaxial tensile loading with 1.7%/s strain rate until failure to characterize elastic
function within the mechanical model. Sixteen specimens were subjected to relaxation
studies over 1,500 seconds to describe time-dependent viscoelastic behavior exhibited
by EOMs. Cyclic loading was performed to validate predictions of the QLV model
characterized from uniaxial tensile loading and relaxation data.
Results: Uniform and highly repeatable stress-strain behavior was observed for 12
specimens extracted from various regions of all EOMs. Since the results from tensile
tests and relaxation tests of all six EOMs were similar, mechanical properties for
each of the six EOMs were assumed to be same. Results from 16 different relaxation
trials illustrated that most stress relaxation occurred during the first 30-60s for 30%
extension. Elastic and reduced relaxation functions were fit (nonlinear least square
fit) to the data, from which a QLV model was assembled and compared with cyclic
loading data. Predictions of the QLV model agreed with observed peak cyclic loading
stress values to within 8% for all specimens and conditions.
Conclusions: Close agreement between the QLV model and both relaxation and
cyclic loading data validates model quantification of EOM mechanical properties,
and will permit development of accurate overall models of mechanics of ocular
motility and strabismus.
CR: L.H. Yoo, None; H. Kim, None; V. Gupta, None; J.L. Demer, None.
Support: NIH Grant EY08313, NIH Grant EY00331
649 - D689
Applying Computer Aided Visualization Techniques to Extra Ocular Muscle
and Eye MRI
U. Zeiger, T.S. Khurana. Physiology and Pennsylvania Muscle Institute, University
of Pennsylvania, Philadelphia, PA.
Purpose: The EOMs are a unique group of muscles that are anatomically and
physiologically distinct from other skeletal muscles. Strikingly, EOMs show differential
susceptibility to disease, exemplified by their preferential sparing in Duchenne’s
Muscular Dystrophy (DMD). Previously, we and others have shown that EOMs have
a unique transcriptome and proteome. In this study we investigated the expression
pattern of microRNAs (miRNAs) at the whole genome level, as they may play a role
in generating the unique EOM allotype.
Methods: We used microRNA microarray chips (LCSciences) covering the sequences
of miRBase 10.0 to define the microRNAome of normal mouse EOM and limb muscle
(TA-tibialis anterior). Data of four independent chips were analysed using background
substraction, normalization and statistics. Online databases, such as miRBase and
TargetScan were used to identify potential miRNA-target pairs.
Results: 74 miRNAs were found to be differentially regulated based on a p-value of
< 0.05 (t-test); 43 miRNAs were up-regulated and 31 miRNAs were down-regulated.
Bioinformatic tools and databases were used to integrate the results with our previous
transcriptomic and proteomic profiling data. Interestingly, miR-155 which we found
to be down-regulated in EOM, has recently been shown to be up-regulated in many
primary muscular disorders, including DMD (Eisenberg et al. PNAS 2007).
Conclusions: In conclusion, our definition of the distinct and unique EOM
microRNAome complements existing data about the molecular make-up of EOM,
which will help to explain their differential sensitivity to disease and may assist in
development of therapeutic strategies.
CR: U. Zeiger, None; T.S. Khurana, None.
Support: NIH Grant EY013862
A.M. Palmowski-Wolfe1A, C. Kober2, I. Berg1B, C. Buitrago-Téllez3, C. Kunz1C, E.W.
Radü1D, S. Wetzel1D. ADepartment of Ophthalmology, BDept. of Cranio-Maxillofacial
Surgery, CDepartment of Cranio-Maxillofacial Surgery, DDepartment of
Neuroradiology, 1University of Basel, Basel, Switzerland; 2Faculty of Life Science,
Germany, HAW Hamburg, Hamburg, Germany; 3Radiological Center Aarau, Spital
Zofingen AG, Zofingen, Switzerland.
Purpose: At ARVO 2008 we had shown computer aided visualization techniques
(CAVT) applied to oculodynamic MRIs of the orbit. Within the extra ocular muscles
(EOM) a devision was seen that was discussed as possibly relating to the obital and the
bulbar layer of the EOM. The purpose of this study is to further improve information
on EOM structure and the eye in an integrated MRI-based approach.
Methods: A threefold strategy was followed. First, a post mortem MRI of a control
subject was analyzed (1.5T, T1 weighted image sequence, 0.6mm layer thickness). 2nd,
we analyzed a 1.5T MRI, done with the Gadolinium based contrast agent Dotarem®,
that was obtained in a tumor patient for evaluation of his underlying disease. 3rd, the
resulting images were compared to those of a living control (1.5 T) whose oculodynamic
MRI movies we presented last year. To enhance visibility of the orbital structures,
special adapted CAVT procedures based on direct volume rendering were applied
to all MRI scans.
Results: For all three approaches, the horizontal and vertical EOM could be clearly
identified. Also, for all approaches, these EOM revealed a two layered structure,
possibly related to the orbital and bulbar layer of the EOM, with some intermediate
tissue in between. In the Dotarem ® MRI, contrast was enhanced in both the presumed
ocular and the presumed bulbar layer of the EOM, but the intermediate zone was
spared, indicating the absence of vascular structures. The enhanced contrast based
on CAVT techniques facilitated identification of sclera, periorbita and muscular
structures. Due to high resolution and image quality of the post mortem MRI, highly
detailed 3D-reconstruction of the orbital anatomy was possible that allowed better
visualization of the oblique muscles and virtual ‘turning’ of the eye in all directions.
In addition, the lens including its attachment to the ciliary fibers could be shown.
Conclusions: Distribution of the contrast medium, Dotarem, in the EOM supports our
previous thesis that 2 layers of the EOM can be shown. We postulate, that these relate
to the orbital and the bulbar layer of the EOM. While 3D-reconstruction of the eye
and its EOM could be greatly improved, differentiation within the connective tissue
at the EOM muscle insertion to the sclera is still subject to future work.
CR: A.M. Palmowski-Wolfe, None; C. Kober, None; I. Berg, None; C. BuitragoTéllez, None; C. Kunz, None; E.W. Radü, None; S. Wetzel, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
646-649
Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706
127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY
650 - D690
Treatment of Dysthyroid Ophthalmopathy With Superior Eye Lid Injection of
Triamcinolone
651 - D691
Clinical and Mri Features in Patients With Dysthyroid Optic Neuropathy
A. Kozaki, T. Inoue, N. Komoto, R. Inoue, Y. Inoue. Ophthalmology, Olympia Eye
Hospital, Tokyo, Japan.
N. Komoto, A. Kozaki, R. Inoue, T. Inoue, T. Maeda, T. Inoue, Y. Inoue. Olympia Eye
Hospital, Shibuya-ku, Japan.
Purpose: This study was conducted to assess the therapeutic efficacy of triamcinoline
injection therapy on lid retraction and swelling associated with dysthyroid
ophthalmopathy.
Methods: The subjects of this study consisted of 29 eyes of 21 cases of dysthyroid
ophthalmopathy that were injected with triamcinoline (40mg) via the conjunctiva
of the upper eyelid for treatment of lid retraction and swelling and then monitored
for three months or more. The subjects consisted of 5 eyes of 3 men and 24 eyes of
18 women. The average age was 43 years. The proptosis as measured by MRI had
an average value of 18.9 mm. To determine side effects of the treatments, palpebral
fissure height, degree of swelling, sizes of the superior rectus muscle (SR) and levator
palpebrae superioris muscle (levator) as determined by MRI were evaluated after
treatment and compared to the respective value before treatment.
Efficacy was evaluated by defining improvement of palpebral fissure height of 1 mm
or more as indicating efficacy against lid retraction and evaluating swelling on the
basis of photographs of the external eye at three months after treatment.
Results: Treatment for lid retraction was performed on 20 eyes while treatment
for swelling was performed on 22 eyes (some eyes underwent treatment for both).
The average palpebral fissure height was 9.6 mm before treatment and 8.7 mm after
treatment, demonstrating a significant decrease (P<0.05). There were 11 eyes (55%) in
which treatment was effective for lid retraction and 19 eyes (86%) in which treatment
was effective for swelling. Although there were no changes observed in surface area of
the SR before and after treatment, that of the levator decreased significantly (P<0.05).
T2-SIR, which is an indicator of inflammatory activity of the extraocular muscle, was
significantly decreased after treatment in both cases (P<0.05). Side effects consisted
of 1 eye exhibiting ocular hypertension (Max.27mmHg) that occurred 3.5 months
after the injection.
Conclusions: Although triamcinoline injection therapy demonstrated somewhat
low efficacy against lid retraction, it was thought to be extremely effective against
eyelid swelling.
CR: N. Komoto, None; A. Kozaki, None; R. Inoue, None; T. Inoue, None; T. Maeda,
None; T. Inoue, None; Y. Inoue, None.
Support: None
Purpose: To define clinical background factors such as thyroid function, systemic
and ocular history, and Magnetic Resonance Imaging (MRI) features in patients with
dysthyroid optic neuropathy (DON).
Methods: The study involved 42 consecutive DON patients (male: 17, female: 25)
of which 72 eyes were examined. All patients underwent visual field and MRI
examination. Mean age was 58 years old.
Results: Patients with thyroid dysfunction included Graves’ disease (40 patients), and
Hashimoto disease (2 patients). Of those with Graves’ disease 2 (5%) were pregnant
females and 4 (10%) had undergone radioiodine treatment. Thyrotropin receptor
antibodies (TRAb) and thyroid stimulating antibodies (TSAb) were found to be present
in 31 of 37 and 38 of 38 patients, respectively. In past history, 6 patients had diabetes
and 4 had hepatitis. Twenty-seven patients (64%) were smokers or ex-smokers. In
ophthalmic examination the proptosis ranged from 12 to 24 mm (average 18.1 mm).
Best corrected visual acuity was less than 20/200 in 15 eyes and 20/25 or better in
19 eyes. All eyes had visual fields abnormalities and reduced critical flicker fusion
frequency (CFF). Optic disc appearance was normal in 36 eyes (50%) with DON.
Orbital imaging using MRI showed apical muscle crowding in all eyes. Forty five
eyes had enlargement of 4 rectus muscles, 21 had enlargement of 3 rectus muscles, 5
had enlargement of 2 rectus muscles, and one only involved the superior rectus. In
T2 enhanced MRI, 25 of 67 eyes had superior ophthalmic vein enhanced.
Conclusions: Patients with DON did not show severe proptosis or abnormal optic
disc features. TSAb should be tested in equivocal DO patients as this was found to
be present in all patients. Radiological evidence of optic nerve compression is the
most useful clinical features in DON, as all eyes showed involvement of at least one
rectus muscle.
CR: A. Kozaki, None; T. Inoue, None; N. Komoto, None; R. Inoue, None; Y. Inoue,
None.
Support: None
652 - D692
Changes of Extraocular Muscle and Orbital Fat After Cervical Sympathectomy
(Iatrogenic Horner’s Syndrome) in Rats
653 - D693
Length and Connectivity of Global Layer (GL) Fibers in Primate Superior
Oblique (SO) Muscle
I.-Y. Chung1, S. Seo1, J. Park1, N. Lee1, H. Kim2, J. Song1. 1Ophthalmology, Gyeongsang
National University, Jinju, Republic of Korea; 2Ophthalmology, Inje University,
Pusan, Republic of Korea.
J.L. Demer1, V. Poukens1, H. Ying2A, X. Shan2B, J. Tian2B, D.S. Zee2B. 1Ophthalmology,
Jules Stein Eye Institute, Los Angeles, CA; AOphthalmology, BNeurology, 2Johns
Hopkins University, Baltimore, MD.
Purpose: To investigate whether cervical sympathectomy (iatrogenic Horner’s
syndrome) induces the morphological changes of extraocular muscles and orbital
fat in rats.
Methods: Unilateral cervical ganglionectomy was done on Sprague-Dawley rats (n=9).
Sympathetic innervation to the eye was destroyed by surgical removal of the right
superior cervical ganglion (superior cervical ganglionectomy; SCGx). The signs of
iatrogenic Horner’s syndrome in these rats included right ptosis and enophthalmos.
After 8 weeks, we extracted bilateral extraocular muscles and orbital fat from rats.
The changes of each tissue were observed and compared using both light and electron
microscopy.
Results: After cervical ganglionectomy, there were no morphological changes between
the control (left) and the experimental (right) orbital fat tissue in rats. However,
the right extraocular muscle (EOM) fibers showed a smaller diameter than the left
under light microscopy. We observed that the number and size of mitochondria were
decreased in the right EOM tissue compared to the left using electron microscopy.
Conclusions: EOM fiber diameter, number, and size of the mitochondria were
significantly attenuated after cervical ganglionectomy in rats. Our data suggest that
extraocular muscle atrophy and changes of mitochondria in EOM may take part in
understanding enophthalmos after cervical sympathectomy.
CR: I.-Y. Chung, None; S. Seo, None; J. Park, None; N. Lee, None; H. Kim, None; J.
Song, None.
Support: None
Purpose: Tension in individual extraocular muscle (EOM) fibers can be related to
overall EOM tension if the lengths and possible series-parallel arrangements of the
fibers are known. Under normal conditions, EOM fibers are too small and numerous
to trace them individually over any significant length. After trochlear neurectomy,
however, some GL fibers in the SO become so markedly hypertrophic that they can
be individually identified and studied. We exploited post-denervation hypertrophy
to trace individual SO fibers throughout the length of the EOM.
Methods: An adult monkey was perfused with formalin 12 mos following unilateral
intracranial trochlear neurectomy (IOVS 2007; 48: 2602 - 2625). The ipsilateral orbit
was embedded whole in paraffin, serially sectioned at 10 micron thickness, and
stained with Masson trichrome. A group of 14 markedly hypertrophic GL fibers
was identified in the SO midbelly. Each fiber was traced from high magnification
micrographs posteriorly to the orbital apex, and anteriorly near trochlear entry, for
a total length of ~19 mm.
Results: All fibers remained within the GL. Six fibers ran the entire ~19 mm SO
length without myomyous junctions, and all fibers were undivided in their posterior
13 mm. Moving anteriorly, there were 2 sets of primary myomyous division into
secondary fiber pairs ~14 mm anterior to the origin, one secondary fiber dividing
again 1 mm further anteriorly. Complex myomyous junctions occurred only 17 - 18
mm anterior to the origin, which is anterior to the globe-optic nerve junction, and
within the sheath surrounding the SO: two pairs of fibers joined into single fibers, a
secondary and tertiary branch of the same fiber rejoined, and two primary and one
secondary fiber joined.
Conclusions: Hypertrophic GL fibers in primate SO extend most or all of retrotrochlear
SO length, and do not insert on orbital layer fibers. About half of hypertrophic GL
fibers are involved in complex, interwoven myomyous junctions limited to a short
extent in the anterior orbit. This suggests that the tension exerted by normal GL fibers
is largely transmitted as oculorotary force to the eye. However, some non-linear force
interaction is to be expected in short anterior segments of GL fibers that are involved
in myomyous junctions.
CR: J.L. Demer, None; V. Poukens, None; H. Ying, None; X. Shan, None; J. Tian,
None; D.S. Zee, None.
Support: NIH Grants EY08313, EY015025, & EY001849
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
650-653
Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706
127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY
654 - D694
The Ultrastructural Changes of Palisade Nerve Endings in the Exotraocular
Muscle After Injection of Botulinum Toxin
655 - D695
Histotopographical Study of Elastic Fibers With Special Reference to the Pulley
System for Extraocular Rectus Muscles
Y.-W. Suh1, M.J. Chang1, S.-H. Kim2, C.-S. Uhm 3, Y.A. Cho1. 1Department of
Ophthalmology, Korea Univ Anam Hospital, Seoul, Republic of Korea;
2
Department of Ophthalmology, Korea Univ Ansan Hospital, Seoul, Republic of
Korea; 3Department of Anatomy, Korea University College of Medicine, Seoul,
Republic of Korea.
H. Osanai1, G. Murakami2, A. Ohtsuka 3, D. Suzuki1, T. Nakagawa4, H. Tatsumi1.
1
Department of Anatomy, Sapporo Medical University School of Medicine,
Sapporo, Japan; 2Iwamizawa Kojinkai Hospital, Iwamizawa, Japan; 3Department
of Anatomy, Okayama University School of Medicine, Okayama, Japan; 4Idai-mae
Nakagawa Eye Clinic, Sapporo, Japan.
Purpose: The purpose of this study was to investigate the ultrastructural changes
of palisade nerve endings after the injection of botulinum toxin A (Botox) into the
extraocular muscles.
Methods: Under the general anesthesia, the medial and superior recti muscles of 12
cats (24 eyes) were exposed. A dose of 5 IU of Botox (0.1 mL) was injected into the
exposed extraocular muscles of one eye and 0.1 ml of normal saline was injected
into the muscles of the other eye. The injection site was about 10 mm proximal to the
myotendinous junction to minimize mechanical trauma of palisade nerve endings. The
myotendinous junctional area was harvested at 1, 4 and 12 weeks after the injection, 4
cats at each time period. The samples were examined under electron microscope. The
myotendinous junction of 4 normal cats were also examined as a normal control.
Results: There was no morphological difference between normal control group and
saline injection group. The proximal portion of palisade nerve endings in control group
was encapsulated structure containing collagen, myelinated and unmyelinated nerve
fiber. At distal palisade endings, myelinated fibers were absent, and encapsulated
nerve endings contained unmyelinated fiber and collagen. At pre-terminal region,
the capsular structure became incomplete. However, axon of unmyelinated fiber
were completely covered with Schwann cell. In botox injection group, separation of
myelin sheath, increase of neurofilament in axons of myelinated and unmyelinated
nerve fiber were observed 1 week after injection, which persisted to 12 weeks. Around
terminal nerve endings, incomplete Schwann cell with axonal exposure were found,
and fibroblast-like change of Schwann cells were also occurred. At 12 weeks, palisade
endings which was not related to the muscle fiber due to Botox induced muscle
atrophy were also found.
Conclusions: Botulinum toxin injected into the extraocular muscle induced
ultrastructural changes of palisade nerve endings. Those alteration can influence
proprioception of the extraocualr muscles. The possibility that those changes can
diminish proprioception of the extraocualr muscle should be considered when
botulinum toxin is used for the treatment of strabismus.
CR: Y.-W. Suh, None; M.J. Chang, None; S.-H. Kim, None; C.-S. Uhm, None; Y.A.
Cho, None.
Support: None
Purpose: To investigate the detailed configuration of the periocular elastic fibers.
Methods: Semiserial paraffin sections were made using 40 whole orbital contents
from 27 elderly cadavers and stained by the aldehyde-fuchsin method.
Results: Periocular tissues were classified into three types according to directions
of the elastic fibers, i.e., tissues containing anteroposteriorly running elastic fibers,
those with mediolateral fibers and, those with meshwork of fibers. Anteroposterior
elastic fiber-dominant tissue was seen in the upper eyelid and newly defined pulley
plate for the medial and lateral recti (MR, LR). In the central part of the inferior rectus
pulley, the mediolateral fibers were seen predominantly. In the pulley plates for the
MR and LR, anteroposteriorly running fibers encased the striated muscle. Tenon’s
capsule and epimysium of the recti were mediolateral fiber-dominant. However, at
the entrance of the muscle terminal where Tenon’s capsule reflects and continues
to the epimysium, composite elastic fibers provided a meshwork-like skeleton. The
elastic mesh was also seen around the lacrimal canaliculi.
Conclusions: The pulley for the recti seemed to be composed of two parts: 1) a
connective tissue plate encasing the recti and 2) specialized Tenon’s capsule at an
entrance or porta of the muscle. For both parts, elastic fibers were major functional
components. Especially, the anteroposterior elastic fibers in the MR and LR pulley
plates seemed to receive anteroposteriorly directed stress and tension from these
striated muscles. The elastic interfaces seemed to prevent any concentration of stress
that would interfere with periocular striated muscle functions including hypothetical
active pulleys.
CR: H. Osanai, None; G. Murakami, None; A. Ohtsuka, None; D. Suzuki, None; T.
Nakagawa, None; H. Tatsumi, None.
Support: None
656 - D696
Correlation Between Eyelid Excursion and Globe Prominence
657 - D697
Analysis of the Extra-Ocular Muscle Paths with the Delft Finite Element Model
of Orbital Mechanics
C. Kum, M.K. Yoon, C.C. Lin, T.J. McCulley. Ophthalmology, UCSF, San Francisco,
CA.
Purpose: Levator muscle function (LF) is often assessed by measuring eyelid excursion.
When reductions in LF are encountered, neuromuscular disease is suspected. Despite
the common use and importance of this clinical sign, little attention has been given
to normal influence factors. In this study we correlate globe prominence with eyelid
excursion.
Methods: The study group (n=58, 22 male, 36 female, range 18 to 90 years of age) was
identified from patients evaluated during the study period. Inclusion criteria were
age >18 and adequate documentation of exophthalmometry measurement results
and levator function, bilaterally. Exclusion criteria included any condition affecting
globe or eyelid position or eyelid function (other than involutional blepharoptosis).
Only right eyes were included in the calculation.
Results: An analysis using Pearson’s correlation coefficient indicates a statistically
significant linear relationship between LF and globe position r(56)=0.54, p<0.001.
For these data, the mean (SD) for LF is 17+/-2.7mm and for globe position 15+/2.2mm. the relationship is defined by the equation y=0.432*x+8.0467 (y=LF and
x=exophthalmometry measurement).
Conclusions: For every 1mm change in axial globe position a mean change in LF of
0.4mm was observed. This reduction in LF with relative enophthalmos should be
considered when interpreting eyelid excursion.
CR: C. Kum, None; M.K. Yoon, None; C.C. Lin, None; T.J. McCulley, None.
Support: None
F.-W. Goudsmit1A, J.W. Moerkerken1A, S. Schutte1A, F.C.T. van der Helm1A, F. van
Keulen1B, H.J. Simonsz2. ABiomechanical Engineering, BPrecision and Microsystems
Engineering., 1Technical University Delft, Delft, The Netherlands; 2Department of
Ophthalmology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Purpose: This investigation studied the importance of sliding surfaces, pressure distribution
and the muscle path with the Delft Finite Element Model of Orbital Mechanics (DFEM). The
path of the EOMs is determined by the tension in the muscle, the stiffness of the muscle itself
and by external forces on the muscle. We investigated, with the DFEM, whether the curved
path could be explained solely by interaction with the fat surrounding the rectus muscles,
rather than through focal mechanical effects.
Methods: The DFEM was extended to incorporate the oblique muscles and optical nerve.
Geometries were obtained from MRI and meshed using 4-noded tetrahedral elements. A
fine mesh was used in areas subjected to large deformations (behind the insertions of the
EOM) and in the narrow area in the apex subjected to large reaction forces. The use of a fine
tetrahedral mesh facilitated calculation and prevented distortion of elements. A contact
algorithm (with zero friction) was employed to model sliding between the interacting
tissues. Sliding was permitted between the fat and EOM, between the fat and optic nerve,
between the fat and the eye. With the model both pressure distribution and muscle paths
were studied.
Results: Sliding permitted more eye rotation than in the previous versions of the model.
The model predicted the pressure distribution in the fat behind the eye (Fig): due to the
use of isotropic homogenous orbital fat, the pressure distribution was more gradual in the
area between the tendon and eye than in reality. During muscle contraction high pressure
gradients were found in the fat between EOM and eye. This resulted in a force orthogonal
to the muscle line of action causing sharp bending (“lateral inflections”) of the muscle
anteriorly.
Conclusion: The model provides insight in the pressure distribution and pressure gradient
in the fat tissue, underlying the curved paths of EOMs. The too gradual pressure distribution
indicates the need for inhomogeneous and/or anisotropic material for the modelling of
the fat.
CR: F.-W. Goudsmit, None; J.W. Moerkerken, None; S. Schutte, None; F.C.T. van der Helm,
None; F. van Keulen, None; H.J. Simonsz, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
654-657
Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706
127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY
658 - D698
Validation of the Delft Finite Element Model of Orbital Mechanics
659 - D699
Analysis of Ex- and Endophthalmos with the Delft Finite Element Model for
Orbital Mechanics
K. de Vries1A, A.M. van Ditten1A, A.G. Dunning1A, S. Ladde1A, S. Schutte1A, C.P. Botha1B,
P. Wielopolski2A, H.J. Simonsz2B. ABioMechanical Engineering, BComputer Graphics,
Dept. Mediamatics, Fac. EEMCS, 1Delft University of Technology, Delft, The
Netherlands; ARadiology, BOphthalmology, 2Erasmus Medical Center, Rotterdam,
The Netherlands.
Purpose: In the Delft Finite Element Model of Orbital Mechanics, material properties
are assigned to the elements based on in-vivo and post mortem measurements. We
performed a validation study using high resolution MRI data and the previously
measured values for viscoelasticity for a comparison with previous in-vivo
measurements of passive rotational stiffness of the eye.
Methods: High quality MRI data of the deformation of the orbital fat were obtained
(see accompanying abstract by Dunning et al.). The orbital fat was segmented (Fig.).
To estimate the displacement of the orbital fat, optical flow analysis (OFA) with the
Demons and B-splines algorithms was employed. A stiffness matrix was build from
finite element 8-node bricks. Material properties of the stiffness matrix were assigned
according to post mortem viscoelasticity measurements on calf orbital fat (G’=250-500
Pa and G’’=80-170 Pa; Schoemaker et al. 2006). Local deformations of the orbital fat
were first multiplied with the stiffness matrix of the fat to calculate the nodal forces.
By multiplying these nodal forces with the deformations again, the energy of the eye
movement was calculated. Dividing this energy by the angle of rotation resulted in
the rotational stiffness. To validate the OFA, MRI control measurements were done
by deformation of a piece of beef.
Results: Stiffness in horizontal eye rotation was 30 - 480 mNmm/deg, comparable to
the stiffness found in in-vivo measurements (120 mNmm/deg). In the OFA validation,
translations were within 6% of the applied value, rotation within 3% and strain
within 4%.
Conclusions: Rotational stiffness of the eye could be derived from imaging data. This
is a step towards the use of preoperative MRI and OFA to adapt the finite element
model to an individual patient.
CR: K. de Vries, None; A.M. van Ditten, None; A.G. Dunning, None; S. Ladde,
None; S. Schutte, None; C.P. Botha, None; P. Wielopolski, None; H.J. Simonsz,
None.
Support: None
660 - D700
Friction in the Orbit
S. Schutte1A, F. van Keulen1B, C.P. Botha1C, F.C.T. van der Helm1A, H.J. Simonsz2.
A
BioMechanical Engineering, BStructural Optimization and Computational
Mechanics, CMediamatics, 1Delft University of Technology, Delft, The Netherlands;
2
Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
Purpose: The human eye is suspended inside the orbit. The interaction between
pressure and tensile forces in the soft tissues keeps the eye in place, while a large
range of rotational motion is enabled. The eye, the extraocular muscles (EOMs),
orbital fat and the optic nerve mechanically interact and exert forces on each other at
every location where they touch. The large range of motion of the eye is facilitated by
sliding at interfaces between tissues. It is currently unknown what the magnitude of
friction is that occurs at these interface layers and how that relates to the energy lost
in viscous deformations of the fat and other tissues.
Methods: The main sliding areas in the orbit are (1) between the sclera and the orbital
fat, (2) between the EOMs and the orbital fat and (3) between the EOMs and the orbital
wall. The total amount of lost energy in eye rotations was measured post mortem in
pigs by passively rotating the eye around the visual axis with a pendulum. This energy
was lost in tissue viscosity and friction at the interface layers. The Delft Finite Element
Model of Orbital Biomechanics, combined with the material properties of the orbital
fat (G’=250-500 Pa and G’’=80-170 Pa;Schoemaker et al. 2006) and deformations of the
tissues found by MRI imaging and optical flow analysis, were used to distinguish
between energy lost in friction and energy lost in viscosity.
Results: The amount of energy that is lost in eye movements due to friction is
small(<10%) compared to the energy lost in viscosity of the tissues. Sliding in the
human body is usually facilitated by a synovial-fluid like substance (mainly consisting
of glycosaminoglycans and glycoproteins) which is known to cause low friction in
joints.
Conclusions: Sliding plays an important role in the orbit and friction at the interface
layers is low. Finite-element modeling enabled estimation of the amount of energy
lost in friction.
CR: S. Schutte, None; F. van Keulen, None; C.P. Botha, None; F.C.T. van der Helm,
None; H.J. Simonsz, None.
Support: None
J.W. Moerkerken1A, F. Goudsmit1A, S. Schutte1A, S.J. Picken1B, F.C.T. van der Helm1A, F.
van Keulen1C, H.J. Simonsz2. ABiomechanical Engineering, BPolymer Materials and
Engineering, CStructural Optimization & Computational Mechanics, 1TU-Delft,
Delft, The Netherlands; 2Ophthalmology, Erasmus Medical Centre, Rotterdam, The
Netherlands.
Purpose: The Delft Finite Element Model for Orbital Mechanics would be well suited
to simulate ex- and endophthalmos like Graves’ disease. In this study the model will
be tested in order to see if the mechanics of these diseases can be simulated.
Methods: Orbital pressure in- and decrease were simulated with expansion and
deflation of part of the tetrahedra constituting the model. To model the orbital
fat we used Herrmann elements. This type of element is used for the modeling of
incompressible materials and provides the hydrostatic pressure as an additional
result. The hydrostatic pressure was considered the resultant of arterial and venous
blood pressure, tissue osmotic pressure and other pressures. For the simulation of
ex- and endophthalmos the orbital volume was increased and decreased; first in the
muscle, then in the fat and finally in the fat and the muscle. Diseases were simulated
with the model: Graves’ disease was modeled by increasing the osmotic pressure
and the volume of the muscles and the orbital fat. Orbital tumor was simulated by
adding orbital fat volume. Cachexia was simulated by reduction of the retrobulbar
fat volume. Finally caroticocavernous fistula was modeled by increasing venous
blood pressure.
Results: Volume and pressure in- and decrease were applied stepwise until the
numerical solution could not be reached by calculation. The model allowed for ±50%
expansion and deflation. Tissue swelling and deflation caused by changes in volume
resulted in ex- and endophthalmos. Adding 50% volume to the orbital fat resulted
in exophthalmos of 6 mm. Pressure increase on the optic nerve was considerable,
pressures up to 15 mmHg were calculated by the model. Reduction of the retrobulbar
fat volume of 50% resulted in endophthalmos of 4 mm.
Conclusions: Ex- and endophthalmos simulations are possible in the Delft Finite
Element Model for Orbital Mechanics and provide insight in the mechanics of various
orbital disorders. The model is now extended to simulate the effect of various surgical
approaches.
CR: J.W. Moerkerken, None; F. Goudsmit, None; S. Schutte, None; S.J. Picken,
None; F.C.T. van der Helm, None; F. van Keulen, None; H.J. Simonsz, None.
Support: None
661 - D701
High-Resolution MRI of Horizontal Gaze Position for Improved Optical Flow
Analysis
A.G. Dunning1A, A.M. van Ditten1A, K. de Vries1A, S. Ladde1A, S. Schutte1A, C.P. Botha1B,
P. Wielopolski2A, H.J. Simonsz2B. ABioMechanical Engineering, BComputer Graphics,
Dept. Mediamatics, Fac. EEMCS, 1Delft University of Technology, Delft, The
Netherlands; ARadiology, BOphthomology, 2Erasmus Medical Center, Rotterdam,
The Netherlands.
Purpose: Long term goal of the Delft Finite Element Model of Orbital Mechanics is to
adapt the model for each individual patient using optical flow analysis (OFA) of MRI
scans taken preoperatively. OFA can estimate displacements and deformations of the
orbital fat by comparing two MRI datasets in different positions of gaze. However, this
MRI data is marred by involuntary head movements and involuntary eye movements.
We obtained high resolution data by limiting head and eye movements.
Methods: A bite board of PVC with dental thermoplast was attached to a stiff MDF
frame that was mounted rigidly to the MRI gantry. To track head movements, MRI
markers were used to detect inadvertent head movement. A LED was rotated at
equidistance in front of the dominant eye in 15 directions of gaze, from 35 degrees
left gaze to 35 degrees right gaze with steps of 5 degrees. The other eye was covered.
Pick-up coils were attached to the frame.
Results: Two 23-year-old males were placed supine in the MRI scanner with a dentalimpression bite board. For 2 minutes 3D T1 weighted scans were made with a Sigma
Excite 3.0T MRI scanner. The successive datasets were analyzed to determine any head
movement. With registration of the markers displacements between successive datasets
were found to be less than 0.1 mm in transversal, 0.5 mm in temporal and 0.3 mm in
vertical direction. The subjects were able to focus on the LED and were able to keep
their eye fixated in the applied direction of gaze: resolution of the scans in extreme
left and right gaze was equal to that of the scan made in primary gaze.
Conclusions: Using this approach high resolution MRI data sets were obtained and
the data sets had sufficient resolution to make high resolution OFA of the deformation
of orbital fat possible (see accompanying abstract by de Vries et al.).
CR: A.G. Dunning, None; A.M. van Ditten, None; K. de Vries, None; S. Ladde,
None; S. Schutte, None; C.P. Botha, None; P. Wielopolski, None; H.J. Simonsz,
None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
658-661
Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706
127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY
662 - D702
Assessment of Blepharospasm and Botulinum Toxin Effects Using
Videonystagmography
663 - D703
Analysis of Microbial Growth in Reconstituted Botulinum Toxin - A Vials
T.H. Osaki, M.H. Osaki, T.H. Osaki, A.E. Sant’Anna, A. Hofling-Lima, M.C. Zorat, R.
Belfort, Jr.. Vision Institute, UNIFESP-Brazil, Sao Paulo, Brazil.
E. Merce1A, G. Casse1A, J.-P. Adenis1A, J.-P. Sauvage1B, P.-Y. Robert1A. AOphtalmology,
B
ENT, 1CHU Dupuytren, LIMOGES, France.
Purpose: The aim of this study was to study blinking parameters using a
videonystagmography device, in order to determine objectively disability, and
to assess the efficiency of botulinum toxin injection in patients with essential
blepharospasm.
Methods: Blinking was studied using the features of pupillary occlusion (PO) as
recorded on a videonystagmography device. In 23 patients presenting with essential
blepharospasm, we studied the frequency, the percentage and the mean duration of
PO, and the longest PO in a 5min test time. Patients were tested prior to botulinum
toxin injection, and respectively 1 month and 3 months after injection. PO of less than
0.3 s and more than 0.3 s were studied apart.
Results: At 1 month after injection, botulinum toxin significantly influenced PO higher
than 0.3 s, both in frequency (9.6/min ± 8.2 on Day0 and 4.7/min ± 7.2 on Month1
(p=0.004)), and in mean duration (0.95 s ± 0,84 on Day0 and 0.58 s ± 0,34 on Month1
(p=0.03)). On the other hand we found no significant effect on PO of less than 0.3 s,
both in frequency (32.4/min ± 28.4 on Day0 and 31.3/min ± 29.0 on Month1 (p=0.7)) and
in mean duration (0.16 s ± 0.04 at Day0 and 0.15 s ± 0.03 at Month1 (p=0.4)). Botulinum
toxin significantly influenced also the mean duration of the longest PO (6,44 s ± 9.4
on Day0 and 1.55 s ± 1.9 on Month1 (p=0.004)) as well as the percentage of PO (29,95%
± 24.6 on Day0 and 13.44% ± 11.1 on Month1 (p=0.003)).
Conclusions: PO can be used as the indirect sign of blinking. Videonystagmography
provides a real-time result, and could be used to objectively evaluate the effect of
botulinum toxin treatment in essential blepharospasm patients.
CR: E. Merce, None; G. Casse, None; J.-P. Adenis, None; J.-P. Sauvage, None; P.-Y.
Robert, None.
Support: None
Purpose: The purpose of this study was to analyze microbial growth in reconstituted
Botulinum toxin - A solutions from vials stored in refrigerator for one month after
use.
Methods: Seventy eight consecutive 100-U vials of Botulinum toxin-A (Botox®) were
reconstituted with 3.0 mL each of normal saline without preservative and were used
in aseptic conditions in blepharospasm and hemifacial spasm patients. The Botulinum
toxin-A solution was used to treat one or two patients in the same day. The same needle
was used for aspiration (just the syringes were replaced and each patient had his own
needle for application). After the applications, each vial was stored in a multiuse
medication refrigerator. Four weeks later, the vials were sent to microbiological
analysis. The contents of the vials were plated by microbiologists using standard
techniques on blood agar, chocolate agar, Sauboraud agar and thioglycolate broth.
Results: Sterility analysis with blood agar, chocolate agar, Sauboraud agar and
thioglycolate broth detected no bacterial growth from the 78 vials of reconstituted
Botulinum toxin-A solutions. There was not fungus growth either.
Conclusions: Even though manufacturers advocate that Botulinum toxin-A shoud
be used within 4 hours after reconstitution, refrigerator storage of medication vials
containing reconstituted botulinum toxin (applied following aseptic precautions),
did not result in microbial contamination of the contents. Therefore, the results
of this study suggest that reconstituted Botulinum toxin-A can be safely stored in
refrigerator for at least 1 month.
CR: T.H. Osaki, None; M.H. Osaki, None; T.H. Osaki, None; A.E. Sant’Anna,
None; A. Hofling-Lima, None; M.C. Zorat, None; R. Belfort, Jr., None.
Support: None
664 - D704
Temporary Management of Involutional Entropion With Application of Octyl-2Cyanoacrylate Liquid Bandage (Band-Aid Liquid)
665 - D705
A Simple, Brow Based Method of Identifying Exophthalmos Correlates with
Established Cases and Detects Unsuspected Cases
M.H. Osaki1, T. Osaki1, T.H. Osaki1,2. 1Ophthalmology, UNIFESP, Sao Paulo, Brazil;
2
Ophthalmology, Santa Casa of Sao Paulo, Sao Paulo, Brazil.
D.S. Bardenstein. Ophthalmology & Pathology, Case Western Reserve University,
Cleveland, OH.
Purpose: Involutional entropion affects basically the lower eyelid and is more
common in older patients. It is associated with several causative factors, including
horizontal lid laxity with attenuation or disinsertion of the lower lid retractors. A
prospective study was designed to evaluate the use of octyl-2-cyanoacrylate liquid
bandage as a temporary treatment in patients awaiting surgical repair for involutional
entropion.
Methods: We evaluated 10 patients (11 lower eyelids) who were awaiting surgical
intervention to correct involutional entropium. The lower eyelid was repositioned
by application of the octyl-2-cyanoacrylate liquid bandage (Band-Aid liquid, Ethicon,
Johnson and Johnson’s, New Jersey, NY, USA) in the lower eyelid, near the lower
orbital rim. Patients were followed at days 1 and 7. Assessment of eyelid correction
and duration of correction were recorded.
Results: All patients presented successful correction at day 1, with significant
improvements in symptoms and signs. The mean duration of action of the octyl-2cyanoacrylate liquid bandage was 3.1±0.9 days. In two patients, adhesion broke at day
2; in five, at day 3; in two, at day 4 and in one, at day 5. No ocular or dermatological
reactions were noted and patients were satisfied with the temporary results.
Conclusions: Octyl-2-cyanoacrylate liquid bandage is a simple and effective method
that provides a potentially simple solution to treat patients with involutional entropion
temporarily, while they are awaiting surgical repair, as well as in patients without
systemic clinical conditions or unwilling to undergo a surgical procedure. It is a
safe, not allergenic and not expensive product that can be used daily (or when the
adhesions break) in these cases.
CR: M.H. Osaki, None; T. Osaki, None; T.H. Osaki, None.
Support: None
Purpose: Expert estimates suggest that 50-85% of patients with Thyroid Eye Disease
(TED) are referred for evaluation later than desired. This is felt to reflect poor detection
of clinical signs of this condition, such as exophthalmos (EXOPH) which can be masked
by concurrent periocular alterations. In addition, most patients at risk for TED are
managed by primary care and internal medicine physicians without special tools such as
exophthalmometers. We sought to develop a simple method to screen for EXOPH, Lateral
Brow Exophthalmometry (LBE) which could be used by most health care providers to
detect EXOPH.
Methods: Patients: 35 Orbit Service patients in whom we suspected EXOPH were included.
Demographic data including: Age, ethnicity and gender were collected. Historic data:
previous suspicion of EXOPH, previous TED, orbit fracture, chronic steroid use andother
causes of EXOPH were obtained Clinical data: Hertel exophthalmometry, lid position
and orbit soft tissue assessment was obtained. Objective EXOPH was defined in 1 of 3
ways: exophthalmometry readings above gender and ethnic norms, showing increase
and alteration of eye position documented from prior photographs. LBE: a rounded
linear rod, was held vertically, resting on the superior orbital rim in the plane of the
corneal apex. LBE was considered positive (+) if the extended line of the posterior rod
surface would intersect the cornea and negative if it was anterior to the corneal apex.
Photodocumentation for the study was then obtained using standard camera orientation
and position. Data analysis: Photographs were printed then coded and examined in a
masked fashion for LBE. LBE was correlated with specialist suspicion of EXOPH, objective
EXOPH and referring provider suspicion of EXOPH.
Results: Patient age ranged from 25-82 years. Ethnicity included Caucasian, African
American, Hispanic and Asian patients. The most common diagnosis was TED, though
in over 30% of cases, EXOPH was unsuspected. Over 90% of patients with + LBE had
objective EXOPH. Over 90% of patients with EXOPH suspected by the specialist showed +
LBE. The exceptions included patients with TED and very deep set orbits. Similarly, over
90% of patients whose EXOPH was not suspected by referring providers had + LBE.
Conclusions: LBE is an extremely simple and safe method for detecting EXOPH requiring
little equipment and training. It is effective both in settings where exophthalmos is very
likely as well as when it is unsuspected. This technique should greatly enhance the
detection of exophthalmos and appropriate referral of patients.
CR: D.S. Bardenstein, None.
Support: NIH EY 11373, Ohio Lions, Research to Prevent Blindness
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
662-665
Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706
127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY
666 - D706
Assessment of the Effect of Ethnicity on the Cosmetic Outcome of Lateral Direct
Brow Lifting
T.J. McCulley, I. Phan, M.K. Yoon, T.N. Hwang. Ophthalmology, University of
California, San Francisco, San Francisco, CA.
Purpose: With the emergence of modern brow lifting techniques, the direct brow
lift is rarely and probably under utilized. This avoidance is due primarily to fear of
unacceptable scarring, particularly in more darkly pigmented individuals. The dermis
of the lateral brow is thinner than medially and therefore less prone to scarring. In
select patients with predominantly lateral brow ptosis, a modified lateral direct brow
lift may serve as a reasonable alternative to larger caliber techniques. In this report
we describe outcomes of ten patients of varying ethnic backgrounds who underwent
lateral direct brow lifts.
Methods: In this retrospective case series, we reviewed 20 brows of 10 consecutive
patients (4 male, 6 female; ages 61 to 77) who underwent a direct lateral brow lift. Main
outcome measure was ethnicity, need for surgical revision and the development of
unacceptable scarring. Surgical technique was as follows: skin incision was made
with a 15-blade scapel and unipolar cautery was used to remove the desired amount
of skin and partial-thickness subcutaneous fat over the lateral half of the ptotic
brow. Inferior dissection within the subcutaneous fat layer allowed mobilization of
the brow superiorly. Closure was performed in three layers: subcutaneous fat using
interrupted 5.0 Vicryl sutures, dermis with interrupted 5.0 Vicryl sutures and skin
with a running 6.0 fast-absorbing plain gut suture.
Results: Patients were of various ethnic backgrounds: Caucasians (n=6), Latinos
(n=2), Filipino (n=1), and Indian (n=1). Follow-up ranged from three to seven months.
No patient required surgical revision. No patient reported or was felt by the treating
physician to have unacceptable scarring. There was no difference in scar visibility in
Caucasian vs non-Caucasian patients (based on patient satisfaction and surgeon review
of post-operative photos). All patients had good functional and cosmetic results.
Conclusions: A lateral direct brow lift is a simple, minimally-invasive surgical
approach that can effectively address lateral brow ptosis and associated lateral
hooding. This small pilot series of patients of varied ethnic backgrounds, suggests
that direct lateral brow lifting may be acceptable even in patients with various degrees
of skin pigmentation.
CR: T.J. McCulley, None; I. Phan, None; M.K. Yoon, None; T.N. Hwang, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
666
Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 925 - 938 / D707 - D720
148. Nerve Fiber Layer in Optic Neuropathy Organizing Section: EY
925 - D707
Prospective Follow-up of Optic Disc Topography and Circumpapillary Retinal
Nerve Fiber Layer Thickness Following Initial Optic Neuritis
926 - D708
One Month Findings Predict Retinal Nerve Fiber Layer (RNFL) Loss at 6
Months After Acute Optic Neuritis
K. Hayashi1, A. Tomidokoro1, M. Yanagisawa1, M. Araie1, M. Wakakura2.
1
Ophthalmology, University of Tokyo, Tokyo, Japan; 2Ophthalmology, Inouye Eye
Hospital, Tokyo, Japan.
S.C. Anderson1, M.J. Kupersmith2, G. Mandel2, R. Kardon1. 1Ophthalmology & Visual
Sciences, VA Medical Center & Univ of Iowa, Iowa City, IA; 2Ophthalmology,
Roosevelt Hospital & New York Eye and Ear Infirmary, New York, NY.
Purpose: To prospectively evaluate the changes in optic nerve head topography and
retinal nerve fiber layer (RNFL) thickness in patients following initial optic neuritis
using the Heidelberg retina tomograph (HRT) II and scanning laser polarimetry
(GDx VCC) .
Methods: Eighteen eyes of 8 unilateral and 5 bilateral patients with an initial episode
of acute optic neuritis were prospectively followed at the 0, 1, 3 and 6 months after
the onset by HRT II, GDx VCC and visual field testing with the Humphrey Field
Analyzer (HFA) 30-2 fast pack.
Results: During the first 3 months after the onset, significant increase in cup area,
cup/disc area ratio and linear cup/disc ratio and significant decrease of rim area in
HRT parameters and significant decrease in TSNIT average, superior average and
inferior average in GDx parameters were found (repeated measure ANOVA, Scheffe
test, P<0.05). These parameters became stable after the month-3. Other HRT and GDx
parameters showed no significant changes during the follow-up. At the month-6,
superior average in GDx was significantly correlated with visual field damage (i.e.
mean deviation of the HFA, R 2=0.506, P=0.0007). In 8 unilateral cases, cup/disc area
ratio and cup shape measure were significantly smaller in the affected eyes than in the
fellow eyes until the month-1 after the onset (P<0.05, paired t-test). These differences
were no longer significant after the month-3. No GDx parameters were significantly
different between the affected and fellow eyes at any time point (P>0.05).
Conclusions: Changes in the optic disc topography and circumpapillary RNFL
thickness were found in the first 3 months following the onset of initial optic neuritis,
which possibly suggest resolving of the acute optic nerve edema and/or gradual
decrease in the number of nerve fibers. Significant correlation between visual field
damage and a GDx parameter may indicate the presence of the axonal damages
after optic neuritis.
CR: K. Hayashi, None; A. Tomidokoro, None; M. Yanagisawa, None; M. Araie,
None; M. Wakakura, None.
Support: None
Purpose: We reported that in acute optic neuritis, RNFL shows acute swelling in
greater than 80% sectors at baseline and thinning in greater than 50% of sectors at
1 month (ARVO 2008). We now report the 3 & 6 month RNFL outcomes of this first
prospective study on patients followed from the onset of acute optic neuritis.
Methods:35 subjects had visual & RNFL assessments using OCT 3 and scanning
laser polarimetry (SLP; enhanced corneal compensation) at entry, 1, 3 & 6 months. We
judged acuity worse than 20/50 or mean deviation (MD) worse than -15 db as severe
vision loss. RNFL thinning for OCT & SLP was significant if 2 clock-hour sectors were
10 microns less than in fellow normal eyes.
Results: RNFL sectors were thinned by SLP in 53% & 76% and by OCT in 73% and 87%
of eyes at 3 & 6 months, respectively. Severe vision loss & sector thinning at 1 month
correlated with thinning of the OCT average RNFL at 6 months(r=.58, p=.006 & r=.54,
p=0.02). The graphs show sector and mean RNFL loss (compared to fellow eyes) over
time. Note swelling of RNFL, common at entry & 1 month, precludes demonstration
of early loss at one month. At 6 months, OCT mean RNFL thinning correlated with
visual acuity (r=.653, p=.001) and MD (r=.725, p=.0001) assessed at that time point.
Conclusions: Sector analysis with fellow eye comparison shows RNFL thinning is
common in optic neuritis, particularly when visual deficits persist. Eyes with severe
vision loss or RNFL thinning at 1 month have worse RNFL loss that continues passed
3 months. This corroborates the importance of the 1 month time point after an acute
optic neuritis.
CR: S.C. Anderson, None; M.J. Kupersmith, Teva Pharmaceutical, C; G. Mandel,
None; R. Kardon, None.
Support: Supported by a Veterans Affairs Merit Rehab Grant and Pearle Vision Fun
927 - D709
Clinical and Ocular Imaging Characteristics of Eyes With Visual Loss Over
Time in Multiple Sclerosis
928 - D710
Structural and Functional Evaluation of the Retinal Nerve Fiber Layer in
Patients With Multiple Sclerosis
E. Bisker1, S. Chang1, A. Conger2, G. Hiremath 3, Y. Dai1, G.-S. Ying1, M. Maguire1, E.
Frohman2, P. Calabresi 3, L. Balcer1. 1University of Pennsylvania School of Medicine,
Philadelphia, PA; 2University of Texas Southwestern Medical Center, Dallas, TX;
3
Johns Hopkins School of Medicine, Baltimore, MD.
E. Garcia-Martin1A,2, V. Pueyo1A,2, J.R. Ara1B, C. Almarcegui1C, J. Martin1B, I. Pinilla1A,2,
M. Idoipe1A,2, F.M. Honrubia1A, J. Fernandez1A. AOphthalmology, BNeurology,
C
Neurophysiology, 1Miguel Servet Hospital, Zaragoza, Spain; 2Instituto Aragones
de Ciencias de la Salud, Zaragoza, Spain.
Purpose: The purpose of this study was to determine the degree of retinal nerve fiber
layer (RNFL) thinning by optical coherence tomography (OCT) that is associated with
losses of low- and high-contrast acuity over time in a multiple sclerosis (MS) cohort.
Visual dysfunction and axonal loss are common in MS. The emergence of OCT has
allowed us to capture the unique structure-function correlations provided by the
anterior visual pathway in MS.
Methods: Patients with MS underwent OCT-3 imaging at baseline and at 6-month
intervals during a mean follow-up period of 1.5 years (range 0.5-3.7) at three academic
centers. RNFL thickness was measured for 360º around the optic disc. Visual function
testing was performed using low-contrast (2.5 and 1.25% levels) and ETDRS acuity
charts. Eyes with comorbid ocular conditions or acute ON within 3 months prior to
testing were excluded.
Results: Among 1,148 patients (2,296 eyes, age 44±11 years) who underwent baseline
assessments, 365 (725 eyes) have participated in longitudinal follow-up. Worsening
of low-contrast acuity was noted in 237 eyes of 123 patients (33% of MS eyes).
Approximately 1/3 of eyes with visual loss had a past history of ON. Two-line (10-letter)
losses of low-contrast acuity were associated, on average, with 1.6 µm decrements in
RNFL thickness over time at 2.5% contrast (p=0.009, GEE models, accounting for age
and within-patient, inter-eye correlations), and 3.7 µm reductions at 1.25% contrast
(p=0.02). Patients with worsening vision were only slightly older (age 45 vs. 43 years),
and had slightly greater disease duration (12 vs. 11 years).
Conclusions: Visual loss occurs in a substantial proportion of MS eyes, and may be
present even in the absence of a history of ON. Reductions in low-contrast acuity
are associated with RNFL thinning over time, suggesting that axonal loss may be a
significant contributor to visual dysfunction in MS.
CR: E. Bisker, None; S. Chang, None; A. Conger, None; G. Hiremath, None; Y.
Dai, None; G.-S. Ying, None; M. Maguire, None; E. Frohman, None; P. Calabresi,
None; L. Balcer, None.
Support: National MS Society PP1115 (Dr. Balcer), National MS Society Translational
Research Partnership TR 3760-A-3 (Drs. Calabresi and Balcer), National Eye Institute
K24 EY 014136 (Dr. Balcer)
Purpose: To evaluate the changes in the retinal nerve fiber layer (RNFL) in patients
with Multiple Sclerosis (MS) by means of ocular imaging technologies and functional
evaluation.
Methods: Forty-six patients with MS (92 eyes) were enrolled in this study. None of the
patients had an optic neuritis episode in at least 6 months prior to the inclusion or during the
follow-up. All patients underwent a complete ophthalmic examination that included visual
acuity (logMAR), colour vision (Ishihara pseudoisochromatic plates), refractive evaluation,
visual field examination, optical coherence tomography (OCT), scanning laser polarimetry
(GDx) and visual evoked potentials (VEP). All the patients were re-evaluated after a period
of 12 months in order to quantify any change in the retinal nerve fiber layer.
Results: All the parameters showed a decrease in the RNFL thickness during the 12-month
follow-up greater than the decrease due to the age in healthy patients, although these changes
were not detected by the standard automated perimetry. Differences were statistically
significant (P<0,05, t test) in the mean and inferior RNFL thickness and macular volume
provided by OCT and in the TSNIT SD provided by GDx. The greater differences were
obtained in the mean RNFL thickness (89.70 µm vs 87.03 µm). Changes in the optic nerve
were detected by structural measurements but not by functional assessments.
Conclusions: The rate of axonal loss observed in patients with MS was greater than that
seen in healthy patients, regardless of the presence of a previous history of optic neuritis.
Progressive axonal loss can be detected in the optic nerve of MS patients. Ocular imaging
technologies are useful tools to evaluate structural abnormalities in the RNFL and changes
in time.
CR: E. Garcia-Martin, None; V. Pueyo, None; J.R. Ara, None; C. Almarcegui, None; J.
Martin, None; I. Pinilla, None; M. Idoipe, None; F.M. Honrubia, None; J. Fernandez,
None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
925-928
Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 925 - 938 / D707 - D720
148. Nerve Fiber Layer in Optic Neuropathy Organizing Section: EY
929 - D711
Relationship Between Optical Coherence Tomography, Pattern
Electroretinogram and Standard Automated Perimetry in Eyes With Temporal
Hemianopia From Chiasmal Compression
930 - D712
Correlation Between Fourier-Domain Optical Coherence Tomography
Measurements of the Macular and Retinal Nerve Fiber Layer and Visual Field
Sensitivity Loss in Patients With Chiasmal Compression
M.L. Monteiro, L.P. Cunha, L.V.F. Costa-Cunha, O.O. Maia, Jr., M.K. Oyamada.
Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil.
L.C. Cunha1, L.P. Cunha2, R.F.S. Malta2, M.L.R. Monteiro2. 1Ophthalmology,
University of Säo Paulo, Sao Paulo, Brazil; 2Ophthalmology, Univ de Sao Paulo, Sao
Paulo, Brazil.
Purpose: To evaluate the relationship between pattern electroretinogram (PERG)
amplitude, optical coherence tomography (OCT) macular and retinal nerve fiber layer
(RNFL) thickness and visual field (VF) loss on standard automated perimetry (SAP)
in eyes with temporal hemianopia from chiasmal compression.
Methods: Forty-one eyes from 41 patients with permanent temporal VF defects
from chiasmal compression and 41 healthy subjects underwent transient full-field
and hemifield (temporal or nasal) stimulation PERG, SAP and time domain-OCT
macular and RNFL thickness measurements (Figure 1). Comparisons were made
using Student’s t test. Deviation from normal VF sensitivity for the central 18° of VF
was expressed in 1/Lambert units. Correlations between measurements were verified
by linear regression analysis.
Results: PERG and OCT measurements were significantly lower in eyes with
temporal hemianopia than in normals. A significant correlation was found between
VF sensitivity loss and full-field or nasal, but not temporal, hemifield PERG amplitude.
Likewise a significant correlation was found between VF sensitivity loss and most
OCT parameters. No significant correlation was observed between OCT and PERG
parameters, except for nasal hemifield amplitude. A significant correlation was
observed between several macular and RNFL thickness parameters.
Conclusions: In patients with chiasmal compression, PERG amplitude and OCT
thickness measurements were significant related to VF loss, but not to each other.
OCT and PERG quantify neuronal loss differently, but both technologies are
useful in understanding structure-function relationship in patients with chiasmal
compression.
Purpose: To test the correlation between fourier-domain (FD) optical coherence tomography
(OCT) measurements of the macular and retinal nerve fiber layer (RNFL) and visual field
sensitivity (VFS) loss on standard automated perimetry (SAP) in eyes with permanent
temporal hemianopia from chiasmal compression.
Methods: 35 patients with permanent temporal visual field (VF) defects and 35 age- and
sex-matched healthy subjects. One eye of each subject was studied.Subjects underwent SAP
(Humphrey) and macular and RNFL thickness measurements with the commercially available
3D OCT-1000 ® (Topcon). Macular thickness measurements were recorded and averaged for
the central area and for each quadrant and half of that area, while RNFL thickness was
measured and averaged for each sector around the optic disc. VFS loss was estimated from
the temporal mean defect (the average of the 22 values of the temporal total deviation plot on
the SAP 24-2 test, excluding the 2 points immediately above and below the blind spot), from
the deviations from normal in six sectors and from the central 16 test points in the VF.
Results: Global and sectoral macular and RNFL thickness parameters differed significantly
between eyes with BA and healthy controls. Correlations were stronger between VFS loss
and quadrantic or hemianopic nasal macular thickness than between VFS loss and sectoral
RNFL thickness. The strongest correlation was observed between macular thickness in
the inferonasal quadrant and VFS loss in the superior temporal central quadrant (ρ=0.78;
R 2=61%; p<0.001).
Conclusions: RNFL and macular thickness measured with FD-OCT were both topographically
correlated with VFS loss in patients with temporal hemianopia from chiasmal compression.
The correlation was stronger with quadrantic macular measurements than with RNFL
thickness measurements. Macular thickness measurements could potentially be used to
quantify neuronal loss in patients with chiasmal compression and could prove clinically
useful in the detection of damage and follow-up of these patients.
CR: M.L. Monteiro, None; L.P. Cunha, None; L.V.F. Costa-Cunha, None; O.O. Maia,
Jr., None; M.K. Oyamada, None.
Support: Fundação de Amparo a Pesquisa do Estado de São Paulo FAPESP (Nos
06/61549-6; 07/54142-0), São Paulo, Brazil and CNPq (No 309709/2007-5), Brasília,
Brazil CT: www.clinicaltrials.gov, 00553761
CR: L.C. Cunha, None; L.P. Cunha, None; R.F.S. Malta, None; M.L.R. Monteiro, None.
Support: None CT: www.clinicaltrials.gov, NCT00607100
931 - D713
Automated Perimetry and Laser Polarimetry in the Assessment of Nerve Fibers
Involvement in Pituitary Adenoma
932 - D714
Differentiating Extra-Cellular Edema From Axonal Thickening in Papilledema
Using OCT and SLP
M. Bordin, G. Milano, C. Maceri, M. Colombo, M. Raimondi, S. Lanteri, L. Bossolesi,
A. Briola, G.C. Rossi. University Eye Clinic of Pavia, IRCCS Policlinico S.Matteo
Fundation, Pavia, Italy.
J.P. Shulman1, G. Mandel2, M.J. Kupersmith1,2. 1The New York Eye and Ear Infirmary,
New York, NY; 2INN, Roosevelt Hospital, New York, NY.
Purpose: To point out the nerve fibers involvement in patients suffering from pituitary
adenomas submitted to transphenoidal surgery.
Methods: 26 patients (50+/-17,9 ys) were selected and submitted to a complete
ophthalmic examination before (baseline visit) and after surgery. The post-intervention
examinations were scheduled at 1, 3, and 6 months. The adenomas were classified
according to Hardy classification. A kinetic test (HFA-II, stimulus I/4) was performed
as a screening and in case of abnormal outcomes a static test 24-2 or 30-2 was carried
out to better determine the visual field (VF) defect. The retinal nerve fiber layer (RNFL)
was evaluated by GDx-VCC.
Results: 3 adenomas were classified as micro and 23 as macro: the dimensions and the
extrasellar extension were very eterogeneous. At baseline visit, none patients suffering
from microadenoma presented VF or RNFL damages: these data were confirmed at 1,
3, and 6 months examinations. Among the macroadenomas, at baseline, 16 subjects
presented normal VF while 22 had normal GDx; 6 presented bitemporal hemianopia at
VF, one of them bilateral and 2 of them had mono-lateral GDx alteration; a mono-lateral
defect of VF was recorded in 3 patients, 2 of them had abnormal GDx. Six months later,
5 patients out of 6 with bilateral VF defect performed a normal VF examination, 2 and
1 of them presented abnormal GDx, bilateral and mono-lateral respectively.
Conclusion: The nerve fiber involvement can be pointed out only for macroadenomas
with extrasellar extension classified as 2/C but a strict correlation between the clinical
defect and anatomical tumor’s characteristics cannot be determined.
Our data suggest that the nerve fibers involvement is mainly due to compression: the
compression doesn’t cause immediately a nerve fiber loss as demonstrated by complete
postoperative recovery of VF. The Gdx is able to point out persistent fiber losses in
patients with recurrent disease and therefore prolonged fiber compression.
CR: M. Bordin, None; G. Milano, None; C. Maceri, None; M. Colombo, None; M.
Raimondi, None; S. Lanteri, None; L. Bossolesi, None; A. Briola, None; G.C. Rossi,
None.
Support: None
Purpose: Ocular coherence tomography (OCT) and scanning laser polarimetry (SLP)
effectively show retinal nerve fiber layer (RNFL) loss in glaucoma and optic neuritis.
Since SLP principally depends on birefringent structures in the retina, it should be
insensitive to extracellular edema. Previous studies have utilized either method
to study swollen optic disks from a variety of etiologies. We investigated subjects
with papilledema due to intracranial hypertension, as an in vivo model for edema
of the RNFL.
Methods: We prospectively studied 18 eyes of 9 subjects, with symptoms of intracranial
hypertension, bilateral clinically apparent papilledema and no visual acuity loss or
optic atrophy. Each subject had complete clinical evaluation, threshold perimetry
using SITA 24-2, and RFNL evaluation with OCT3 and enhanced corneal compensation
GDx. RNFL was judged thicker (by OCT) or had increased retardance (by SLP) when
greater than the upper 95th percentile of the provided age matched controls. We
calculated a percent (%) thickness ratio: Study Eye Thickness/Control Eye Thickness,
for OCT and SLP.
Results: Global RNFL averages were thicker in 10 eyes of 7 subjects by OCT and in 4
eyes in 3 subjects by SLP. Compared to our controls for OCT (114 μ as 95th percentile),
13 eyes in 8 subjects were thickened. Using the Zeiss controls for SLP (72.7 μ as 95th
percentile), 4 eyes in 3 subjects had increased retardance. RNLF swelling (better
demonstrated by OCT, Table) was more prevalent in superior and inferior quadrants.
For the 13 eyes with OCT swelling, the mean for OCT%-SLP% was 78 (range 14-235)
and provided a relative measure of edema. There was no correlation between the
degree of swelling and visual field or visual acuity.
Conclusions: Intracranial hypertension associated RNFL swelling occurs in part due
to extracellular edema that is better demonstrated by OCT. SLP appears to better reflect
changes within the axons (i.e. axonal dilation) that comprise the optic nerve.
CR: J.P. Shulman, None; G. Mandel, None; M.J. Kupersmith, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
929-932
Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 925 - 938 / D707 - D720
148. Nerve Fiber Layer in Optic Neuropathy Organizing Section: EY
933 - D715
Retinal Thickness and Visual Function in Kjer Optic Atrophy
A.A. Reis1,2, C. Mateus1, E.D. Silva1,2, M. Castelo-Branco1. 1Visual Neurosciences, IBILI,
Faculty of Medicine, Coimbra, Portugal; 2Ophthalmology, University Hospital,
Coimbra, Portugal.
Purpose: To correlate multifocal electroretinographic responses with retinal thickness
in patients with Kjer optic atrophy.
Methods: Objective visual function was assessed by multifocal electroretinography
(RetiScan - Roland Consult, Germany) in a population of 26 eyes of 13 patients with
autosomal dominant optic atrophy. Retinal thickness measurements were also obtained
in these patients by optical coherence tomography (Stratus OCT-3, Humphrey, USA).
These data were compared with age-matched controls and were also correlated.
Statistical analysis was performed using ANOVA at a significance level of p<0.05.
Results: MfERG shows a significant decrease in amplitude in all rings of eccentricity
(R1:p=0.042; R2:p=0.002; R3:p=0.0003; R4:p=0.0013; R5:p=0.0005). Decreased retinal
thickness was also found in all 9 regions within 6 mm of the central retina (p<0.0001
for all pericentral regions and p=0.009 for the central one). A significant correlation
between the grand averages of mfERG amplitude and retinal thickness was found
(r=0.721; p=0.0305). Posthoc analysis by rings, yielded marginal significance only in
ring 2 (r=0.636; p=0.056).
Conclusions: Our results suggest that visual impairment in Kjer optic atrophy is
not confined to the ganglion cells / nerve fiber layer (as widely described in the
literature), but also by concomitant structural and functional damage in outer retinal
compartments.
CR: A.A. Reis, None; C. Mateus, None; E.D. Silva, None; M. Castelo-Branco,
None.
Support: None
934 - D716
Longitudinal Evaluation of Retinal Nerve Fiber Layer Thickness in Leber’s
Hereditary Optic Neuropathy Carriers Shows Relevant Variability Over Time
P. Barboni1, C.D. Ramos2, G. Savini1, M. Carbonelli1, F. Sadun 3, A. De Negri4, A.
Berezovsky2, S.R. Salomao2, A.A. Sadun5, V. Carelli6. 1Studio d’Azeglio, Bologna,
Italy; 2Ophthalmology, UNIFESP, São Paulo, Brazil; 3Ospedale San Giovanni,
Tivoli, Italy; 4Azienda San Camillo-Forlanini, Rome, Italy; 5Doheny Eye Institute
and Department of Ophthalmology, Los Angeles, CA; 6Dipartimento di Scienze
Neurologiche, Bologna, Italy.
Purpose: To analyze longitudinally the retinal nerve fiber layer (RNFL) thickness of
Leber’s Hereditary Optic Neuropathy carriers (LHON-carriers) by means of optical
coherence tomography (OCT).
Methods: Sixty-two LHON-carriers were investigated during the Fifth, Sixth, Seventh
and Eight International Field Investigation in Colatina, Brazil, between 2005 and
2008. All subjects are maternally related and belong to the same LHON Brazilian
family carrying the homoplasmic 11778/ND4 mtDNA mutation on a haplogroup J
background. The RNFL thickness was analyzed by StratusOCT using the 3.4 RNFL
acquisition protocol. Changes of RNFL thickness for each quadrant and the 360°
average were considered true (rather than the consequence of intersession variability of
StratusOCT measurements) if they were higher than the previously reported tolerance
limit of the instrument, defined as the intersession standard deviation multiplied by
2.77 (according to Budenz et al, Ophthalmology 2008;115:661). Only one eye for each
subject was considered for analysis.
Results: Twenty-three subjects had completed all annual examinations and were
included in this study. Eleven of them (48%) showed RNFL thickness changes in at least
one quadrant; in 4 eyes (17%) RNFL changes were observed in at least two quadrants.
The incidence of RNFL changes was higher in the superior and inferior quadrants (5
eyes, 22%), than in the temporal (4 eyes, 18%) and nasal (2 eyes, 9%) quadrants. RNFL
changes were not correlated to the optic disc area.
Discussion: Along a follow-up of 4 years LHON-carriers showed changes of RNFL
thickness in half of cases, suggesting that their optic nerves fibers undergo subclinical
changes that do not necessarily lead to the acute phase of the disease.
CR: P. Barboni, None; C.D. Ramos, None; G. Savini, None; M. Carbonelli, None; F.
Sadun, None; A. De Negri, None; A. Berezovsky, None; S.R. Salomao, None; A.A.
Sadun, None; V. Carelli, None.
Support: None
935 - D717
Correlation of Automated Visual Fields, Spectral Domain and Time Domain
Optical Coherence Tomography Findings in Eyes With Optic Nerve Head
Drusen
936 - D718
Comparison of Optical Coherence Tomography Retinal Nerve Fiber Layer and
Macular Thickness Measurements for the Detection of Progressive Axonal Loss
Following Traumatic Optic Neuropathy
V.A. Shah, N.R. Sabates, A.J. Bonham, R. Krishna. Ophthalmology, University
Missouri Kansas City, Kansas City, MO.
L.P. Cunha, L.V.F. Costa-Cunha, R.F.S. Malta, M.L.R. Monteiro. Ophthalmology, Univ
de Sao Paulo, Sao Paulo, Brazil.
Purpose: Correlation of peripapillary retinal nerve fiber layer thickness by spectral
domain & time domain optical coherence tomography (OCT) with automated visual
fields in patient with optic nerve head drusen.
Methods: This is an institutional review board approved prospective study of 16 eyes
with optic nerve head drusen & controls. After informed consent, complete medical
history, ophthalmology examination, B scan ultrasonography,automated visual field,
peripapillary retinal nerve fiber layer analysis (spectral and time domain OCT) was
performed on all subjects (healthy and patients with optic nerve head drusens).
Results: Spectral domain & time domain OCT measured RNFLT were significantly
predictive of automated visual fields defects for superior and inferior segments (p<
0.05) in patients with optic nerve head drusen. The superior and inferior retinal nerve
fiber layer thickness were significantly thinner in optic nerve head drusen eyes as
compared to controls (p<0.01). Across normal patients and those with disease (n = 21),
there were strong statistically significant correlations between spectral domain and
time domain OCT measurements for both superior (r = 0.94, p < .001) and inferior (r
= 0.91, p < .001) retinal nerve fiber layer readings. Regression analyses demonstrated
that disease status does not affect the correlation for superior (p = .350) or inferior
(p = .227) retinal nerve fiber layer. . Drusen grade & maximum intra ocular pressure
were not predictive of automated visual fields defect.
Conclusions: Spectral domain & time domain OCT reliably measures retinal nerve
fiber layer thickness correlating with automated visual fields.
Purpose: to compare the ability of optical coherence tomography (OCT) retinal nerve
fiber layer and macular thickness measurements for detection of progressive axonal
loss following acute traumatic optic neuropathy (TON) in a longitudinal study.
Methods: three patients with unilateral TON were evaluated sequentially after trauma.
Macular and retinal nerve fiber layer (RNFL) thickness measurements were obtained
using OCT weekly for five weeks and around the twelfth week after trauma.
Results: all patients showed progressive macular and RNFL thickness reduction.
RNFL loss was apparent 2 weeks after trauma and became significant around 4 weeks
and much more prominent 12 weeks after trauma. Macular thickness measurements
showed reduction at 5 weeks that became significant only 12 weeks after trauma.
When compared to the initial measurement macular thickness average reduction rate
at the 12th week was 13.58% while peripapilary RNFL thickness average reduction
rate was 59.31%.
Conclusions: RNFL thickness measurements show greater and faster retinal neural
reduction when compared macular thickness measurements in traumatic optic
neuropathy. Although both measurements reduce significantly after trauma and
both can be used for quantification of axonal loss, macular thickness measurements
reduction is much smaller when compared to RNFL thickness measurements.
CR: V.A. Shah, None; N.R. Sabates, None; A.J. Bonham, None; R. Krishna, None.
Support: None
CR: L.P. Cunha, None; L.V.F. Costa-Cunha, None; R.F.S. Malta, None; M.L.R.
Monteiro, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
933-936
Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 925 - 938 / D707 - D720
148. Nerve Fiber Layer in Optic Neuropathy Organizing Section: EY
937 - D719
Optic Nerve and Retinal Nerve Fiber Layer Studied by Oct, Gdx and Hrt in
Patients With Type I Diabetes
938 - D720
Multifocal Photopic Negative Response (mfPhNR) and Retinal Nerve Fiber
Layer Thickness (RNFLT) in Normals and the Patients With Optic Nerve
Lesions
M. Idoipe Corta, III1,2, E. Garcia-Martin1,2, I. Pinilla1,2, L. Gil-Arribas1,2, E. Abecia1, A.
Ferreras1, V. Pueyo1,2. 1Ophthalmology, Hospital Miguel Servet, Zaragoza, Spain;
2
Instituto Aragones de Ciencias de la Salud, Zaragoza, Spain.
A. Kamei1, E. Nagasaka2. 1Ari Eye Clinic, Oshu-Mizusawa, Japan; 2Mayo Corp.,
Inazawa, Japan.
Purpose: To determine the ability of Confocal Scanning Laser Ophthalmoscope (SLO),
Heidelberg Retina Tomograph (HRT) and Scanning Laser Polarimeter (GDx-VCC) to
detect optic nerve neuropathy and loss of the retinal nerve fiber layer (RFNL) previous
the development of retinopathy in in patients with type I diabetes.
Methods: Comparative cross-sectional study. Fifty eyes of 50 healthy subjects and 50
eyes of 50 patients with type I diabetes mellitus were studied. Ophthalmic examination
of diabetic patients showed no retinopathy. One eye per patient was randomly selected
for the study. The nerve fiber layer thickness was measured using polarimetry (GDxVCC) (NFA, Laser Diagnostic Technologies Inc, San Diego, CA, USA) and with Optical
Coherence Tomography OCT (OCT2: Carl Zeiss Meditec, Dublin, California, USA). The
optic disc was measured with HRT3 (HRT3: Heidelberg Engineering, Dossenheim,
Germany).
Results: The control group was formed by 16 women, 34 men, aged 24-40 yr (mean
28.89 ±4.68). Diabetic patients were 16 women and 34 men, aged 25.56 yr (±10.49).
Mean period from the onset of diabetes was 12.8 years (SD 9.40). None of the diabetic
group had changes at the fundus examination. No differences were found in GDx or
OCT measuremens between control and diabetic group. We did found differences
in HRT measurements including linear cup/disc ratio, cup shape measure, rim area,
rim volume, height variation contour, and mean RNFL thickness.
Conclusions: HRT can detect optic disc topography abnormalities in type I diabetes
mellitus patients before the development of diabetic retinopathy. Neither GDx or
OCT are able to find differences in the retinal nerve fiber layer thickness in diabetic
patients without retinopathy. These data support the importance of the neuropathy
in diabetic patients and the need of increasing our knowledge about its pathogenesis
and risk factor.
CR: M. Idoipe Corta, III, None; E. Garcia-Martin, None; I. Pinilla, None; L. GilArribas, None; E. Abecia, None; A. Ferreras, None; V. Pueyo, None.
Support: None
Purpose: To evaluate the interrelation of mfPhNR and RNFLT in the superior and
inferior region in normals and patients with optic nerve lesion.
Methods: Ten eyes of ten volunteers with normal vision and six eyes of three 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 all the superior and inferior
regions was analyzed.
RNFLT was measured using Cirrus HD-OCT. The average RNFLT in all superior and
inferior quadrants was applied for analysis.
Results: There was a correlation between the amplitude of the mfPhNR in the superior
region and RNFLT in the inferior quadrant (R=0.7575, P=0.0230) in normals. On the
other hand, there was no correlation between the amplitude of the mfPhNR in the
inferior region and RNFLT in the superior region in normals. The amplitude of mfPhNR
in the eyes with optic nerve lesions decreased not only in the RNFLT decreasing
quadrant but also the normal RNFLT quadrant. In unaffected eye of the patient with
optic nerve lesion, the amplitude of mfPhNR was within normal range. In more
affected eyes and less affected eyes with NTG, the amplitude of mfPhNR decreased
in RNFLT decreasing quadrants but also normal RNFLT quadrants.
Conclusions: There is a different correlation between the amplitude of the mfPhNR
and RNFLT in superior and inferior quadrants in normals. The amplitude of mfPhNR
decreased even in patients with normal RNFLT quadrants.
CR: A. Kamei, None; E. Nagasaka, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
937-938
Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 1127 - 1137 / D1089 - D1099
157. Strabismus Surgery Organizing Section: EY Contributing Section: RE
1127 - D1089
Pseudo-Brown’s Syndrome With Superior Rectus Muscle Recession: A New
Complication of Vertical Muscle Surgery
1128 - D1090
Downshoot in Infra-adduction in Strabismus With A-pattern: Post Surgical
Evolution Following Selected Superior Oblique Surgical Weakening Procedures
J.A. Galvin, S.M. Archer. Ophthalmology, University of Michigan, Ann Arbor, MI.
E.A. Urrets Zavalia1, J.I. Torrealday1, F.A. Esposito1, H.M. Serra2, J.A. Urrets-Zavalia1.
1
Ophthalmology, University Clinic Reina Fabiola, Universidad Catolica de
Cordoba, Cordoba, Argentina; 2CIBICI-CONICET, Faculty of Chemical Sciences,
Universidad Nacional de Cordoba, Cordoba, Argentina.
Purpose: Superior rectus surgery may cause unique complications including ptosis
and eyelid retraction. We describe a new strabismus complication causing a profound
limitation of elevation in adduction, simulating a Brown’s syndrome. We present
a small series of patients with an unusual complication of superior rectus muscle
insertion into the superior oblique tendon after recession.
Methods: Retrospective chart review.
Results: Three patients with the operative finding of superior rectus muscle insertion
into the anterior border of the superior oblique muscle--without direct attachment to
the sclera--after previous superior rectus muscle recession were identified. Findings
included a large hypotropia of the affected eye with duction and version findings
suggesting Brown’s syndrome. Exploration, separation from the superior oblique
tendon and advancement of the superior rectus muscle with direct scleral attachment
was corrective in two cases. The third case required further resection of the superior
rectus muscle and superior oblique tenotomy. Discussion: Recession of the superior
rectus muscle can result in a mechanical strabismus, which resembles Brown’s
syndrome. Patients demonstrate a limitation of elevation due to (1) lack of a direct
scleral insertion and (2) tension on the superior oblique tendon on attempted upgaze.
Additional factors that may promote this complication include the hang-back recession
technique, perhaps with inadequate lysis of the frenulum between the superior rectus
and superior oblique muscles.
Conclusions: Identification of the etiology of a vertical deviation resembling a Brown’s
syndrome following superior rectus recession surgery is important. Non-scleral
insertion of the superior rectus muscle into the superior oblique tendon should be
suspected when an unexpected large hypotropia occurs after superior rectus muscle
recession.
CR: J.A. Galvin, None; S.M. Archer, None.
Support: Heed Ophthalmic Foundation
Purpose: To evaluate the occurrence of postsurgical true/pseudo superior oblique
muscle overaction (SOOA) following treatment of A-pattern strabismus and its possible
causes.
Methods: 30 patients with A-pattern strabismus and symmetric SOOA were
consecutively treated with 3 different superior oblique muscle (SOM) weakening
surgical procedures according to degree of presurgical anisotropia and SOOA. 19
patients underwent a posterior partial tenectomy (PPT), 6 a temporal tenotomy (TT)
at 4mm from scleral insertion and 5 a posterior transposition recession (PTR). The
same procedure was performed in both eyes of a same patient.
Results: Mean postsurgical correction of A-anisotropia was 73.9% in patients treated
with PPT, 83.3% with TT and 84% with PTR. Persistence of downshoot in infra-aduction
(DSIA) (true/pseudo SOOA) occurred in 12 out of 19 patients (63%) treated with PPT, in
2 of 6 (33%) with TT and in 5 of 5 (100%) of those treated with PTR. Mean DSIA correction
was 56.4% in patients treated with PPT, 79.9% with TT and 25% with PTR.
Conclusions: A high prevalence of postsurgical DSIA in patients with A-pattern treated
with selective surgical procedures performed on SOM was observed. Apparently all
3 different surgical procedures used were useful in reducing horizontal action of
SOM, with less effect on its vertical action. Eliminating A-pattern, natural vertical
movements promoted by SOM such as depression in infra-adduction and slight
elevatio in infra-abduction would become more evident, giving the impression of
SOM hyperfunction exacerbation. As the least traumatic procedure TT gave the
lowest occurence of DSIA.
CR: E.A. Urrets Zavalia, None; J.I. Torrealday, None; F.A. Esposito, None; H.M.
Serra, None; J.A. Urrets-Zavalia, None.
Support: None
1129 - D1091
Clinical, Tomographic and Genetic Study of Two Mexican Patients With
Congenital Fibrosis of the Extraocular Muscles
1130 - D1092
Inferior Oblique Surgery for Restrictive Strabismus in Patients with Thyroid
Orbitopathy
N. Pereyra-Munoz1A, C.E. Murillo-Correa1B, S. Flores-Limas1C, J.C. Zenteno1D.
A
Integral Ophthalmology, BStrabismus, CRadiology, DGenetics-Research Unit,
1
Ophthalmology Institute “Fundación Conde de Valenciana”, Mexico City, Mexico.
S.A. Newman. Ophthalmology, University of Virginia, Charlottesville, VA.
Purpose: Congenital fibrosis of the extraocular muscles (CFEOM) is a non-progressive
disorder of ocular motility characterized by restrictive ophthalmoplegia and
congenital blepharoptosis. Three types of CFEOM exist. CFEOM1 and CFEOM3
are due to mutations in KIF21A, a gene located in chromosome 12q12 and encoding
a member of the kinesin family of proteins involved in the transport of essential
cellular components along axonal and dendritic microtubules. Mutations in KIF21A
are believed to cause alterations in axonal routing and transportation which lead to
ocular motility disorders. KIF21A arginine residue at position 954 is altered in more
than 80% of all individuals with KIF21A mutations reported to date. The analysis
of CFEOM patients from distinct ethnic groups would help to establish the relative
frequency of specific KIF21A mutations. The purpose of this study was to identify
mutations in the KIF21A gene in two Mexican patients with CFEOM.
Methods: Two unrelated patients with CFEOM consulting at the Ophthalmology
Institute “Fundación Conde de Valenciana” in Mexico-City were included. A complete
ophthalmologic examination, orbital CT and analysis of the KIF21A gene by means
of PCR and automated sequencing, were performed in both subjects.
Results: Both cases were sporadic. Patient 1 was a 19 year old girl with a best corrected
visual acuity (BCVA) of 20/25 in the right eye (OD) and 20/40 in the left eye (OS).
She had undergone two eye surgeries before presenting. She showed limitations in
all gaze directions, particularly in supraversion, and bilateral ptosis. CT evidenced
bilateral thinning of the superior muscular complexes. Patient 2 was a 9 year old
girl with a BCVA of 20/70 OD and 20/40 OS. She had bilateral limitations in all gaze
directions, paradoxical convergence, occlusion nystagmus, esotropia and bilateral
ptosis. CT showed fibrosis of the extraocular muscles. In both patients, genetic analysis
disclosed an identical c.2860C>T point mutation, predicting a change from arginine
to tryptophan at residue 954 (R954W).
Conclusions: We report two cases of Mexican patients with CFEOM, which had an
R954W mutation in KIF21A. Our results support previous findings indicating that
recurrent, de novo mutations at KIF21A R954 are the most common CFEOM cause
in different populations.
CR: N. Pereyra-Munoz, None; C.E. Murillo-Correa, None; S. Flores-Limas,
None; J.C. Zenteno, None.
Support: Patronage of the “Fundación Conde de Valenciana”
Purpose: Thyroid orbitopathy (TO) is the most common cause of restrictive strabismus.
Patients often present with vertical and/or horizontal double vision due to restriction
involving most commonly the inferior and medial rectus muscles. Traditional muscle
surgery involves release of the tight muscles. Previous literature has described frequent
need for secondary operations and over correction incidence of up to 50%. Recognizing
that the tight muscles are also limited in their excursion; it was proposed that operating
on the better moving eye particularly the inferior oblique (IO) might produce an
improvement in binocularity and decrease the incidence of over correction.
Methods: A total of 42 patients with restrictive strabismus due to TO treated at the
University of Virginia over 12 years with inferior oblique surgery were retrospectively
reviewed.
Results: Thirty nine patients were treated initially with inferior oblique surgery. Of
these 28 patients required secondary procedures. Four patients were over corrected
and a total of 24 patients were under corrected. A total of 3 patients were treated
with IO surgery as a secondary procedure. Five patients were treated with additional
muscle procedures at the time of IO surgery (3 medial rectus (MR), 1 superior rectus
(SR) and 1 lateral rectus (LR)). At the time of last follow up ranging from 6 months
to 8 years 23 had no diplopia, 2 had minimal diplopia and 2 had persistent diplopia.
All but two were completely functional.
Conclusions: Inferior oblique surgery by balancing the overall excursion of extraocular
muscles in thyroid patients may produce binocularity in primary position and down
reading gaze. There appears to be an increase in the area of binocular single visual
and a decrease in the incidence of over correction with the use of inferior oblique
surgery. The use of the Hess screen and binocular single vision fields is helpful in
assessment and planning of surgery in these patients.
CR: S.A. Newman, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1127-1130
Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 1127 - 1137 / D1089 - D1099
157. Strabismus Surgery Organizing Section: EY Contributing Section: RE
1131 - D1093
Modern Management of Hypertropia in Thyroid Eye Disease With Adjustable
Sutures
1132 - D1094
Surgical Results of Lateral Recti-Recession and Monocular Recess-Resect in
Exotropia for Patients With a Dominant Fxating Eye
N. Mirza-George1, G. Binenbaum1, N.J. Volpe2. 1Ophthalmology, Children’s Hospital of
Philadelphia, Philadelphia, PA; 2Ophthalmology, Scheie Eye Institute/University of
Pennsylvania, Philadelphia, PA.
B. Dufay-Dupar, B. Roussat, F.-X. Brousseaud, T. Rodallec, R. Adam, O. Laplace, J.-P.
Nordmann. Ophthalmology, NIH, Paris, France.
Purpose: Restrictive vertical strabismus due to thyroid eye disease (TED) is challenging
to correct. We report the clinical outcomes of a management approach employing
adjustable sutures.
Methods: Retrospective case series . 41 subjects with TED and hypertropia underwent
unilateral or bilateral adjustable-suture inferior rectus recession (IRRec) by one surgeon
(NJV). Surgery variably included non-adjustable superior rectus recession (SRRec) on
the hypertropic eye. Intraoperative forced-ductions determined number of vertical
muscles recessed. Post-adjustment goal was orthotropia or undercorrection in primary
gaze without hyperdeviation in downgaze ipsilateral to IRRec. Outcomes were vertical
alignment within 5pd of orthotropia, diplopia, reoperation, and need for prisms.
Results: Forty subjects had preoperative diplopia. Median preoperative primaryposition deviation was 12pd (range 4-50). 21(66%) subjects had unilateral IRRec; 14(34%)
bilateral. 17(41%) subjects had SRRec. 8 patients were adjusted same-day, 33 next-day.
On long-term follow-up (mean 41wks), no subjects had diplopia, although two subjects
required re-operation (4.9%/95%CI 0.6-16.5) and 13(32%) required prism (9/13 were
<5pd). 8 of these 15 subjects had overcorrections. 33(80%) subjects had successful
vertical alignment after one surgery, of which 21 were orthotropic. In multivariate
regression, day of adjustment, number of vertical muscles recessed, and previous
decompression did not affect outcomes.
Conclusions: Previous TED studies report a reoperation rate of 17-45%. Our findings
suggest that using adjustable-sutures, operating on multiple muscles if indicated, and
planning for postoperative IR weakening can reduce this rate. While 1/3 of patients
required prisms, long-term deviations were small. We conclude that TED-associated
hypertropia can be successfully managed with unilateral and bilateral adjustablesuture IRRec, with or without supplemental SRRec.
CR: N. Mirza-George, None; G. Binenbaum, None; N.J. Volpe, None.
Support: NIH Grant EY015398
1133 - D1095
Same Day Triple Therapy With Reduced Fluence Photodynamic Therapy,
Intravitreal Dexamethasone and Bevacizumab in Patients With Neovascular
Age-Related Macular Degeneration
Purpose: To report the median term outcome of the results between bilateral recession
of the lateral recti (BLR) and monocular recess-resect procedure (RR) for the correction
of exotropia of patients with a dominant fixating eye.
Methods: The medical records of 70 patients with exotropia who underwent surgery
for exotropia from January 2002 to April 2008 and followed up for more than 6 months
were reviewed retrospectively. The inclusion criteria were: basic type exotropia or
and pseudo-divergence excess with or without normal stereopsis, with an invariably
fixating eye. These patients underwent BLR or unilateral RR procedures on the
nondominant eye; surgical outcomes were compared. An outcome was considered
satisfactory if there was between 10 prism diopters of exophoria/tropia and 10 prism
diopters of esophoria/tropia at 6 months after surgery.
Results: In the BLR group, success was obtained in 57.1% of the patients (20 of the 35
patients). There was no case of overcorrection in the BLR group. In the RR group, 27 of
the 35 patients (77.1%) had a satisfactory outcome; 3 patients (8.6%) were overcorrected.
All overcorrected patients in the RR group had poor stereoacuity. The surgical success
was significantly higher in the RR group than in the BLR group (P <0.01, MannWhitney U test).
Conclusions: For the correction of exotropia of patients with a dominant fixating eye
the unilateral RR procedure seems to be better than BLR recession surgery. When no
dominant eye is shown the two procedures can be considered to be equally effective.
But, the overcorrection rate was higher in the unilateral RR group.
CR: B. Dufay-Dupar, None; B. Roussat, None; F.-X. Brousseaud, None; T. Rodallec,
None; R. Adam, None; O. Laplace, None; J.-P. Nordmann, None.
Support: None
1134 - D1096
Age-Related Immune Defects Causing Endophthalmitis After Strabismus
Surgery in Young Children or in Elderly
S.M. Couch, S.J. Bakri, C.A. McCannel, A.O. Edwards. Ophthalmology, Mayo Clinic,
Rochester, MN.
Purpose: To report the results of same day triple therapy with reduced fluence
photodynamic therapy (PDT), intravitreal dexamethasone, and bevacizumab in
patients with neovascular age-related macular degeneration (AMD).
Methods: Retrospective case series of thirty one patients with neovascular AMD. All
patients who received same day triple therapy with reduced fluence photodynamic
therapy (25 J/cm2), intravitreal dexamethasone (200mcg) and intravitreal bevacizumab
(1.25mg). Main outcome measures were Snellen visual acuity (VA), central macular
thickness (CMT) on optical coherence tomography (OCT), need for retreatment,
intraocular pressure, and endophthalmitis occurrence.
Results: Average followup for the thirty one patients was 13.7 months. In all patients,
mean baseline VA was 20/80 and vision at final followup was 20/60 (p=0.69). In patients
who received previous treatment for exudative AMD (n=18), mean baseline VA was
20/100 and vision at final followup was 20/100 (p=0.31). In treatment-naïve patients
(n=13), mean baseline VA was 20/60 and vision at final followup was 20/40 (p=0.31). In
all patients, mean CMT was 293 um at baseline and 245 um at final followup (p=0.053).
In previously treated patients (n=18) mean CMT was 325 um at baseline and 265 um at
final followup (p=0.10). In treatment-naïve patients, mean CMT was 249 um at baseline
(n=13) and 218 um at final followup (p=0.34). Previously treated patients required more
anti-VEGF injections (mean = 3.6) than treatment-naïve patient (mean = 0.8), but the
mean number of repeat triple therapy treatments was 0.3 in both groups. Changes in
intraocular pressure and endophthalmitis were not observed during followup.
Conclusions: Same-day combination therapy with reduced fluence PDT, intravitreal
bevacizumab and dexamethasone preserved visual acuity and decreased macular
thickness in patient with and without previous anti-VEGF therapy. Same-day triple
therapy may reduce the number of anti-VEGF injections in some patients and stabilize
vision in some patients not responding to anti-VEGF therapy.
CR: S.M. Couch, None; S.J. Bakri, Novartis, Genentech, Alcon, C; C.A. McCannel,
Genentech, C; A.O. Edwards, None.
Support: None
H.J. Simonsz1A, M.R. Batstra2, C.M. Mooy1B, W.B. van Leeuwen1C, K.U. Löffler3, N.G.
Hartwig1D. AOphthalmology, BPathology, CMedical Microbiology and Infectious
Diseases, DPediatrics, 1Erasmus Medical Center, Rotterdam, Netherlands;
2
Immunology, Reinier de Graaf Hospital, Delft, Netherlands; 3University Eye
Clinic, Bonn, Germany.
Purpose: We previously reported (ARVO 07) on 14 cases of endophthalmitis after strabismus
surgery. These were either children under 6 who underwent a medial rectus recession and
had a poor outcome, or elderly over 65 who had been operated previously on the involved
eye and had a favorable outcome. We sought for age-related differences in immune response
that could underlie the 2 distinct presentations.
Methods: The index case was a 2-year-old girl with a previous right abducens palsy after otitis
media with 41.9°C. An encapsulated, mucoid H. influenzae was cultured from the vitreous
and, after enucleation 2 years later, from purulent discharge of the socket. Homology was
examined with multi locus sequence typing (MLST). Her immune response and that of 3
other children and 2 elderly were assessed. Specifically, Pneumococcus IgG type 1, 3, 4, 5, 9
and 23 (against bacterial capsular polysaccharides) were measured. Enucleated eyes of the
index case, of 2 other children and 1 elderly were studied histopathologically.
Results: MLST showed that the 2 strains of H. influenzae from the index case were not related:
6 of 7 alleles were different. She had had no retinal detachment until vitrectomy 3 weeks
later. Pathology showed no perforation: the deeper layers of the sclera were undisturbed.
Underneath the suture tract the channel for the long posterior ciliary artery was located,
however. Levels of all 6 types of Pneumococcus IgG were < 0.35 ug/ml (2 out of 6 may be
considered normal). A 12-year-old boy, operated at 4, had 4 types < 0.35 ug/ml; his eye is
phtysic. A 6-year-old girl, operated at 3, had 2 types and a 16-year-old boy, operated at 2,
had 3 types < 0.35 ug/ml; both enucleated phtysic eyes had an area of transscleral scarring
compatible with perforation. A 65-year-old woman had 2 types and a 71-year-old man had
1 type < 0.35 ug/ml, scleral perforation had occurred in both cases.
Conclusions: The type of endophthalmitis after strabismus surgery that occurs in young
children can be caused, in part, by immune defects of the type that resolves when the
IgG armentarium unfolds. A contaminated suture may then cause it even without scleral
perforation. Although the immune response against capsular polysaccharides decays in
senescence, we could not detect this in 2 elderly cases. As all 8 cases in young children
originated from medial rectus recessions and some had had upper respiratory infections,
the possibility of reflux from the lacrimal sac needs further study.
CR: H.J. Simonsz, None; M.R. Batstra, None; C.M. Mooy, None; W.B. van Leeuwen,
None; K.U. Löffler, None; N.G. Hartwig, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1131-1134
Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 1127 - 1137 / D1089 - D1099
157. Strabismus Surgery Organizing Section: EY Contributing Section: RE
1135 - D1097
Recurrent Horizontal Strabismus with the Same or Larger Angle of
Misalignment
1136 - D1098
Strabismus Surgery Under Lidocaine 2% Gel
I. Zundane, S. Bruneau, R. Adam, E. Constantini, E. Tiberghien, B. Dufay-Dupar, F.-X.
Brousseaud, T. Rodallec, J.-P. Nordmann. Ophthalmology, Hospital XV-XX, Paris,
France.
S.P. Christiansen, C.T. Bramante. Ophthalmology, University of Minnesota,
Minneapolis, MN.
Purpose: To investigate potential predisposing factors for postoperative horizontal
strabismus that recurs with an equivalent or larger angle.
Methods: The records of 1358 patients who underwent strabismus surgery by one
surgeon were reviewed. Patients who met eligibility criteria and who had recurrent
strabismus with a postoperative angle that matched or exceeded the original deviation
were analyzed. All pre- and postoperative alignment testing was performed by the
same surgeon with children wearing their full hyperopic correction if indicated.
Preoperative clinical characteristics were assessed.
Results: Sixteen patients (1.2%) met eligibility requirements. Of these, 4 (25%) had
restrictive strabismus and 4 (25%) had paralytic strabismus. These were not analyzed
further. Eight of 16 patients (50%) had non-restrictive, non-paralytic esotropia (7) or
exotropia (1). Among these, 5 of 8 (62.5%) had a distance < near discrepancy of more
than 10 prism diopters (PD). The mean preoperative deviation was 23 PD at distance
and 35 PD at near. Three of 8 (37.5%) had hyperopia > 4.00 diopters. For all 16 patients,
mean age at the time of initial surgery was 28 years (range 3.4-67.3, median 18.8). All
patients underwent further surgery. Postoperative alignment improved to < 10 PD
in 10 of 16 patients (62.5%) after their final surgery.
Conclusions: Recurrent horizontal strabismus that matches or exceeds the original
deviation is rare but may be more common in patients with restrictive and paralytic
forms of strabismus or in those with significant distance-near discrepancy. These data
must be interpreted with caution due to the small number of patients.
CR: S.P. Christiansen, None; C.T. Bramante, None.
Support: Research to Prevent Blindness, Inc
Purpose: to evaluate lidocaine 2% gel efficacity in the strabismus. surgery
Methods: 20 patients with horizontal muscles strabismus 4 with esotropia, 6 with
exotropia were included in the study. Deviation angle was from 35 prisms to 50 prisms.
). The surgery was performed on 2 to 3 horizontal muscles per patient (mean 2.75).
All were adult patients. 19 cases were 1st surgery, 1 case was 2nd surgery. All cases
were operated under lidocaine 2% gel local anesthesia. The perception of discomfort
or pain was evaluated by all patients between 1 (very painful) and 10 (no subjective
discomfort) during the surgery and the patients satisfaction was estimated the same
way on the day one. The difficulty of performing the procedure was evaluated by two
operating surgeons between 1 (very difficult) and 4 (very easy to perform the surgical
intervention). The patient’s compliance during surgery was evaluated between 1
(no compliance) and 10 (good compliance). The time of stay in operating room was
compared between 20 cases of topical anesthesia by adult patients of this study and 20
cases of standard strabismus surgery cases under general anesthesia of adult patients
performed by the same surgeons. The satisfaction after surgical manipulation was
evaluated as well on day 1 on the scale between 1 (a lot of subjective discomfort) and
10 (very satisfied).
Results: the mean patient satisfaction was 8.5 during the surgery, the range was
6 to 10. The group of patients under local anesthesia presented higher subjective
satisfaction rate as the patients under general anesthesia (p> 0.02). The difficulty of
performing the surgery was evaluated by the first surgeon 3 (the range was 2 to 4).
Three patients needed to be potentialised with Midazolam during the surgery. 1 patient
potentialized by Midazolam was previously a drug abuser. The compliance of the
patient correlated with difficulty of performing the surgery and patient satisfaction
(p>0.02) and the surgeon’s experience with this surgical technique an important
factor of the success.
Conclusions: carefull selection of adult patients permits to perform the strabismus
surgery under local anesthesia of Lidocaine 2% gel.
CR: I. Zundane, None; S. Bruneau, None; R. Adam, None; E. Constantini, None; E.
Tiberghien, None; B. Dufay-Dupar, None; F.-X. Brousseaud, None; T. Rodallec,
None; J.-P. Nordmann, None.
Support: None CT: If Other, enter the registry site and corresponding number
1137 - D1099
Dose and Pattern of Strabismus Surgery Under Topical Anesthesia
J. Tejedor1,2, C. Ogallar1. 1Ophthalmology, Hospital Ramón y Cajal, Madrid, Spain;
2
Faculty, Universidad Autónoma de Madrid, Madrid, Spain.
Purpose: To compare surgical dose of strabismus surgery using topical anesthesiaadjusted dose in cooperative patients, with theoretical commonly used classic
guidelines dosage.
Methods: Forty cooperative patients, requiring surgery for esotropia (n=20) or
exotropia (n=20), were operated using topical anesthesia. Restrictive and paralytic
strabismus cases were excluded. Visual acuity, refraction, binocular function
(Bagolini lenses and synoptophore), and deviation angle (prism and cover test) were
determined in all patients. The amount of surgery under topical anesthesia was
adjusted intraoperatively. Linear regression models for topical and theoretical dosage
were adjusted and compared. We also studied theoretical dosage versus difference
between topical and theoretical dosage.
Results: The amount of surgery required using topical anesthesia in patients with
esotropia was 5.77 mm (95%CI: 5.26-6.28), i.e., 2.6 mm less on average (95%CI: 2.39-2.80)
than indicated by theoretical guidelines. In exotropic patients, the total amount of
surgery required using topical anesthesia was 10.52 mm (95%CI: 9.53-11.51), 0.92 mm
less on average (95% CI: 0.13-1.71) than indicated in table guidelines. Intercept and
slope values were significantly different between a dose/surgery linear regression
model with topical anesthesia and a theoretical model, for patients with esotropia.
Motor success rates with topical anesthesia were similar in esotropia and exotropia
(17/20, 85%).
Conclusions: Topical anesthesia may be particularly advantageous in cooperative
patients with esotropia, decreasing time and risk of additional surgery.
CR: J. Tejedor, None; C. Ogallar, None.
Support: FIS Grant PI 040643
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1135-1137
Monday, May 4, 8:30 AM - 10:15 AM Palm A Paper Session Program Number Range: 1204 - 1210
202. Strabismus I Organizing Section: EY
1204 - 8:30AM
Improvement in Health Related Quality of Life in Adults Following Strabismus
Surgery
1205 - 8:45AM
Long-Term Effectiveness of Treatments for Symptomatic Convergence
Insufficiency in Children 9 to 17 Years Old
J.M. Holmes, S.R. Hatt, D.A. Leske. Department of Ophthalmology, Mayo Clinic,
Rochester, MN.
M. Scheiman1, M. Kulp2, G. Mitchell2, S. Cotter3, M. Rouse3, R. Hertle4, Convergence
Insufficiency Treatment Trial Study Group. 1Eye Institute-Coll of Optometry,
Pennsylvania College of Optometry, Philadelphia, PA; 2Coll of Optometry, Ohio
State University, Columbus, OH; 3Southern California College of Optometry,
Fullerton, CA; 4Children’s Hospital Of Pittsburgh, Pittsburgh, PA.
Purpose: To compare the responsiveness of 2 health related quality of life (HRQOL)
instruments, the new strabismus-specific AS-20 and the NEI VFQ-25, in adults
undergoing strabismus surgery.
Methods: 37 adults with strabismus (aged 21 to 82 years, median 51) who were
successfully aligned postoperatively, completed the AS-20 and VFQ-25 preoperatively
and a median of 8 weeks postoperatively (range 4 to 13 weeks). 25 patients had diplopia,
and 12 had no diplopia. Each questionnaire (overall and subscales) was scaled from 0
(worst HRQOL) to 100 (best HRQOL). 95% limits of agreement (LOA) for both AS-20
and VFQ-25 were defined in a previous test-retest study and real change in HRQOL
was defined as change exceeding the 95% LOA. We compared proportions of patients
showing real change.
Results: Overall, more patients showed an improvement in AS-20 score compared to
composite VFQ-25 score (21 [58%] of 37 vs 11 [30%]; P=0.01). Analyzing by whether the
patient had diplopia or not, more patients without diplopia showed improvement in
AS-20 than VFQ-25 (7 [58%] of 12 vs 0 of 12). On AS-20 subscales, 8 (67%) of 12 improved
on the psychosocial subscale and 1 (8%) improved on the function subscale. On the
5 potentially useful VFQ-25 subscales (identified in a previous study), only 2 (17%)
of 12 non-diplopic patients improved on Vision-specific (VS) role difficulties and VS
social functioning subscales, and only 1 (8%) improved on VS dependancy; no patients
showed improvement on the VS mental health and Peripheral vision subscales. In
contrast, for diplopic patients, the AS-20 and VFQ-25 were more comparable. Similar
proportions showed improvement in composite AS-20 and VFQ-25 scores (14 [56%]
of 25 vs 11 [44%]; P=0.3). On AS-20 subscales, 10 (40%) of diplopic patients improved
on the function subscale and 6 (24%) improved on the psychosocial subscale. On the
5 potentially useful VFQ-25 subscales, the proportion of diplopic patients showing
improvement ranged from 54% to 12%: VS role difficulties: 13 (54%) of 25, VS mental
health: 12 (48%), VS dependancy: 8 (32%); VS social functioning: 5 (20%), and Peripheral
vision 3 (12%).
Conclusions: For non-diplopic patients, the AS-20 is more responsive than the VFQ25 to improvement in HRQOL following strabismus surgery. For diplopic patients
both questionnaires are responsive. The new strabismus-specific AS-20 questionnaire
is useful over the entire spectrum of strabismus and addresses both function and
psychosocial issues.
CR: J.M. Holmes, None; S.R. Hatt, None; D.A. Leske, None.
Support: NIH Grant EY015799 (JMH), Research to Prevent Blindness, Inc., and Mayo
Foundation
Purpose: To assess the long-term stability of improvements in symptoms and signs in
9- to 17-year-old children enrolled in the Convergence Insufficiency Treatment Trial
who were asymptomatic after treatment for convergence insufficiency (CI).
Methods: 79 patients who were asymptomatic after a 12-week therapy program for
CI [33 in office-based vergence/accommodative therapy (OBVAT), 18 in home-based
pencil push-ups (HBPP), 12 in home-based computer vergence/accommodative therapy
and pencil push-ups (HBCVAT+), and 16 in office-based placebo therapy (OBPT)] were
followed for 1 year. Maintenance therapy was prescribed for the first 6 months and
no treatment for the second 6 months. Symptoms and clinical signs were measured
6 months and 1 year after completion of the 12-week therapy program. Outcome
measures were the mean change on the Convergence Insufficiency Symptom Survey
(CISS), near point of convergence (NPC), positive fusional vergence at near (PFV), and
proportions of patients who remained asymptomatic on the CISS or who were classified
as successful or improved based on a composite measure of CISS, NPC, and PFV.
Results: 1-year follow-up visit completion rate was 89% (32/33 OBVAT, 15/18 HBPP,
10/12 HBCVAT+, and 13/16 OBPT) with no significant differences between groups
(p = 0.26). Eight patients (10%) reported seeking alternative treatment subsequent
to the completion of the 12-week therapy program but prior to the 1-year followup visit (1 OBVAT, 3 HBPP, 2 HBCVAT+, and 2 OBPT). Among the remaining 62
patients (31 OBVAT, 12 HBPP, 8 HBCVAT+, and 11 OBPT), there were no significant
changes in the CISS, NPC, or PFV in any treatment group during the 1-year follow-up
(p-values ≥ 0.077). Twenty-seven of the 32 patients (84%) in the OBVAT group remained
asymptomatic and, using the composite measure, 87% remained either successful
(56%) or improved (31%) 1-year post-treatment.
Conclusions: Improvements in symptoms and clinical signs occurring after officebased vergence/accommodative therapy with home reinforcement are maintained in
most children aged 9 to 17 years for at least 1 year after discontinuing treatment.
CR: M. Scheiman, None; M. Kulp, None; G. Mitchell, None; S. Cotter, None; M.
Rouse, None; R. Hertle, None.
Support: U10 EY014713-01A2 CT: www.clinicaltrials.gov, NCT00338611
1206 - 9:00AM
Residual Strabismus in Children Following Resolution of Cranial Nerve Palsies
Affecting Ocular Motility
1207 - 9:15AM
Accommodative and Vergence Responses to Conflicting Blur and Disparity
Stimuli During Visual Development
M.L. Bratton1A, M.E. Hoehn1B, N.C. Kerr1B. ACollege of Medicine, BDepartment of
Ophthalmology, 1University of Tennessee, Memphis, TN.
S.R. Bharadwaj, T.R. Candy. School of Optometry, Indiana Univ Bloomington,
Bloomington, IN.
Purpose: Children with cranial nerve palsies (CNP) are at risk for residual strabismus
after their motility deficits resolve. We sought to evaluate if this was true for CNP
secondary to a CNS malignancy.
Methods: We identified 106 children with CN III, IV, and/or VI palsies who were treated
for CNS malignancies. A retrospective chart review was conducted to determine the
presence or absence of residual strabismus following resolution of motility deficits.
Results: Forty-eight of 106 children resolved their motility deficits with treatment
of their CNS malignancy. One child had a CN III palsy, 6 had CN IV palsies (one was
bilateral), 40 patients had CN VI palsies (16 were bilateral), and one child had two
different CNP in the same eye (CN IV and VI). Of the 48 children who resolved their
motility deficits, 35 patients had residual strabismus (Group A). Only 13 resolved their
strabismus (Group B). Average angle of strabismus before motility deficits resolved
was 33.8 prism diopters (PD) in Group A and 20.6 PD in Group B (not a statistically
significant difference). There was no significant difference between Group A and B
with regards to age at diagnosis or length of follow-up.
Conclusions: Our findings indicate that the majority of children with resolved motility
deficits from a CNP after treatment for CNS malignancy will be left with residual
strabismus, regardless of age at diagnosis, angle of strabismus at presentation, or type
of CNP. Children with CNP secondary to CNS malignancy need ophthalmic care
after motility deficits resolve, as they are likely to have residual strabismus, which
can put the child at risk for visual system problems related to loss of binocularity,
including amblyopia.
CR: M.L. Bratton, None; M.E. Hoehn, None; N.C. Kerr, None.
Support: None
Purpose: Clear and single vision requires coordinated accommodation and vergence
motor responses. The accommodative demand of infants is typically greater than that
of adults due to hyperopia, while their vergence demand is smaller due to reduced
inter-pupillary distance. The relationship between these demands also changes with
growth of the eye and head, requiring some form of flexibility in the interaction
between accommodation and vergence to maintain clear and single vision. Here,
we assessed the capacity of the developing visual system to overcome short-term
experimentally induced conflicts between accommodation and vergence demands.
Methods: Accommodative and vergence responses were measured using a
PowerRefractor (25Hz). 101 subjects (2.0months to 40.1years) experienced binocular
step changes in either blur (-2D lenses) or disparity (2MA base-out prisms) while they
watched a high contrast cartoon movie at 80cms. 14 and 12 subjects also experienced
1D or MA and 3D or MA step changes in blur and disparity demands, respectively.
The strengths of accommodation-vergence cross-coupling (AC/A and CA/C ratios)
was also measured in 38 and 20 subjects respectively (3.2months to 11.1years) under
conditions of open-loop disparity and blur cues.
Results: The frequency of response to both lenses and prisms increased significantly
with age (p<0.001), with no significant difference between lenses and prisms (p=0.38).
The direct response gain (i.e. accommodation to lenses and vergence to prisms)
increased significantly with age (p<0.001), with a slightly but significantly larger
response to prisms (Mean+/-SEM: 0.71+/-0.02) than to lenses (0.58+/-0.02) at all ages
(p<0.001). Across all ages (p=0.52), the coupled response gain (i.e. vergence to lenses
and accommodation to prisms) was much smaller for both lenses (0.10+/-0.01) and
prisms (0.17+/-0.03) and they were significantly smaller than (p<0.001) and poorly
correlated with the subject’s AC/A (r=0.25) and CA/C (r=0.21) ratios. Unlike response
frequency (p=0.14) and coupled response gain (p=0.73), the direct response gain
decreased significantly with increased stimulus demand for both lenses and prisms
(both p<0.001).
Conclusions: The typically developing visual system can, at least partially, compensate
for conflicts in blur and disparity demands by independently modulating its
accommodative and vergence responses, suggesting short-term flexibility in the
interaction between the two motor systems.
CR: S.R. Bharadwaj, None; T.R. Candy, None.
Support: NIH Grant EY014460 (TRC)
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1204-1207
Monday, May 4, 8:30 AM - 10:15 AM Palm A Paper Session Program Number Range: 1204 - 1210
202. Strabismus I Organizing Section: EY
1208 - 9:30AM
Defining the Critical Period for Smooth Pursuit Development in Infant
Primates: Effects of Binocular Decorrelation
1209 - 9:45AM
Prevalence of the Ocular Motor Signs of the Infantile Strabismus Complex in
Children with and Without Cerebral Visual Pathway White Matter Injury
K.T. Le1, P. Foeller2, D. Bradley3, L. Tychsen2, A.M. Wong1. 1Faculty of Medicine,
University of Toronto, Toronto, ON, Canada; 2Washington University in St. Louis,
St. Louis, MO; 3Yerkes Regional Primate Research, Atlanta, GA.
S. Khanna1A, A. Sharma1B, F. Ghasia1A, T. Inder1C, L. Tychsen1A. AOphthalmology,
B
Neuroradiology, CPediatrics, 1Washington University, St Louis, MO.
Purpose: Infantile esotropia is typically associated with nasotemporal asymmetry of
smooth pursuit, manifested as a bias favoring nasalward target motion when viewing
monocularly. Earlier studies by our group have found that an optical strabismus
induced in non-human primates during an early critical period of development causes
smooth pursuit asymmetry when image decorrelation occurs between the first 3-12
weeks of life (equivalent of age 3-12 months in humans). The purpose of this study
was to further delineate the critical period of smooth pursuit development.
Methods: Binocular image decorrelation was imposed on infant macaques by fitting
them with prism goggles on day 1 of life. The goggles were removed after 3 (n=2), 6
(n=2), 9 (n=2) or 12 weeks (n=3), emulating surgical repair of strabismus in humans
at 3, 6, 9 and 12 months of age, respectively. Two control monkeys wore plano lenses.
Several months after goggle removal, horizontal smooth pursuit was recorded using
binocular search coils and a nasal-bias index (NBI) was calculated.
Results: Each animal in the 9- and 12-week groups developed nasotemporal asymmetry
of smooth pursuit when viewing with either eye. The smooth pursuit in 3- and 6-week
duration monkeys was symmetric and indistinguishable from the controls. NBI were
negligible or slightly negative in the control, 3- and 6-week monkeys, but positive and
substantially greater (9-14x) in the 9-and 12-week monkeys (ANOVA, p<0.05).
Conclusions: We further delineate the critical period of smooth pursuit development;
it appears to occur between 6 and 9 weeks postnatally in monkeys. Our findings
suggest that surgical repair of infantile esotropia in humans would be most beneficial
before the age 6 months.
CR: K.T. Le, None; P. Foeller, None; D. Bradley, None; L. Tychsen, None; A.M.
Wong, None.
Support: NIH Grant EY10214 (L.T.), Walt and Lilly Disney Award for Amblyopia
Research from Research to Prevent Blindness (L.T.), Grant MOP 67104 (A.W.), CIHR
New Investigator Award (A.W.)
Purpose: To determine if the prevalence of the ocular motor signs of the infantile
strabismus complex increases as a function of the severity and extent of cerebral
visual pathway white matter injury (CVPWMI). CVP was defined as the posterior
optic radiations and the splenium of the corpus callosum.
Methods: MRIs obtained ≥ age 2 yrs were scored using a standardized system
(CVPWMI graded 1-3) in 67 children (mean GA 31 wks; mean BW 1885 g) who had
WMI detectable as periventricular leukomalacia with or without reduced volume of
the splenium. Masked ophthalmologic and orthoptic examinations were performed
on the CVPWMI group and a GA-matched control group who had normal MRIs.
Results: Infantile strabismus (primary eso: exo 3.5:1) was documented in 60% of grade
1, 77% of grade 2, and 86% of grade 3 CVPWMI children, respectively. Other ocular
motor signs of the complex increased with CVPWMI grades 1-3: latent/manifest
latent nystagmus (20%; 47%; 46%), DVD (13%; 26%; 27%), and nasotemporal pursuit/
OKN asymmetry (13%; 37%, 37%). The prevalence of each of these signs in the control
group was ≤ 8% (ANOVA and chi-square < 0.05). CVPWMI grade related also to the
prevalence of retrograde (axial and sectoral) optic neuropathy (6%, 27%, 36%).
Conclusions: Children who suffer CVPWMI develop the ocular motor signs of the
infantile strabismus complex at rates substantially exceeding those of non-CVPWMI
children. The prevalence of the signs increases with CVPWMI severity. These findings
reinforce the conclusion that the infantile strabismus complex is caused by prenatal/
perinatal damage to cerebral visuomotor pathways.
CR: S. Khanna, None; A. Sharma, None; F. Ghasia, None; T. Inder, None; L. Tychsen,
None.
Support: Gustav and Louise Pfeiffer Foundation Award (FG,LT)
1210 - 10:00AM
Reduced Quality of Life in Childhood Intermittent Exotropia
S.R. Hatt, D.A. Leske, T. Yamada, E.A. Bradley, J.M. Holmes. Department of
Ophthalmology, Mayo Clinic, Rochester, MN.
Purpose: To assess health related quality of life (HRQOL) in children with intermittent
exotropia (IXT) and their parents.
Methods: Individual interviews with children with IXT and one of their parents
generated items for Child, Proxy (parental assessment of child’s HRQOL), and Parent
questionnaires, which were then refined using standard item reduction methodology.
Three final derived IXT questionnaires (IXTQ): Child, Proxy, and Parent (12, 12, and
17 items respectively) were administered to 33 children with IXT (median 8 years,
range 5-15) and one of their parents, and 49 control children (median 8 years; range
5-13) and one of their parents. Children in the control group had no strabismus or
amblyopia. A Likert type scale ranging from ‘never’ (score 100, best HRQOL) to ‘almost
always’ (score 0, worst HRQOL) was used for responses. Wilcoxon tests were used to
compare median scores between IXT and control groups.
Results: Median Child IXTQ scores were significantly lower (worse HRQOL) in the IXT
group compared with the control group: 85 (range 54-100) versus 92 (50-100); P=0.04.
Median Proxy IXTQ scores were significantly lower for IXT children than controls:
83 (54-100) versus 98 (65-100); P<0.0001. The most discriminating questions for both
Child and Proxy questionnaires related to shutting one eye in the sun and comments
from others. Median Parent IXTQ scores were also significantly lower in the IXT group
compared with the control group: 68 (range 24-100) versus 93 (49-100); P<0.0001. All
Parent questions discriminated well between IXT and control groups, relating to
possible surgery, psychosocial concerns, and function concerns of the child
Conclusions: We have developed and validated a new 3-part patient-derived HRQOL
questionnaire for children with IXT and their parents. These questionnaires detect
reduced HRQOL in children with IXT both as reported by the child themselves and
as perceived by their parents. Childhood IXT also affects the HRQOL of the parents.
The IXTQ HRQOL questionnaires may prove useful in the clinical assessment of IXT
and for clinical trials.
CR: S.R. Hatt, None; D.A. Leske, None; T. Yamada, None; E.A. Bradley, None; J.M.
Holmes, None.
Support: NIH Grants EY015799 (JMH) and EY013844 (EAB), Research to Prevent
Blindness, Inc., and Mayo Foundation
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1208-1210
Monday, May 4, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 1436 - 1447 / A326 - A337
222. Neuro-Ophthalmology: Treatment Organizing Section: EY
1436 - A326
Ocular Myasthenia Gravis: Treatment Successes and Failures in Patients With
Long Term Follow Up
1437 - A327
Effect of Transcorneal Electrical Stimulation(tes) in Patients With Traumatic
Optic Neuropathy(ton)
M. Kurli1, M.J. Kupersmith1,2. 1Ophthalmology, New York Eye and Ear Infirmary,
New York, NY; 2Institute of Neurology and Neurosurgery, Roosevelt Hospital, New
York, NY.
H. Shimojyo1A, T. Fujikado1B, T. Morimoto1A, Y. Okawa1B, K. Matsushita1A, Y. Kitaguti1B,
Y. Tano1A. AOphthalmology, BApplied Visual Science, 1Osaka Univ Medical School,
Suita, Japan.
Purpose: We previously reported prednisone reduced the frequency of generalized
myasthenia (GMG) and controlled diplopia, without major adverse effects at 2 years,
in patients with ocular myasthenia gravis (OMG). Questions remain whether study
subjects had long standing disease-biasing results towards a steroid benefit and if
prednisone merely delayed GMG onset.
Methods: Record review of a referral neuro-ophthalmology service OMG database
for patients who had follow up > 4 years or until GMG developed. We studied the
effect of prednisone on GMG incidence and control of ocular symptoms. Generally,
patients with diplopia were recommended for prednisone therapy. Most remained on
daily 2.5-10 mg to prevent diplopia. We compared the results for prednisone-treated
and ‘untreated’ (pyridostigmine only) patients.
Results: Of 87 patients, 55 were in the prednisone-treated and 32 were in the ‘untreated’
groups. GMG developed in 7 (13%) of prednisone-treated (OR 0.41; 95 % CI: 0.22, 0.76)
and in 16 (50%) of ‘untreated’ (OR 2.78; 95% CI: 1.68, 4.60) patients. After OMG onset,
GMG developed at a mean of 5.8 years and 0.22 years in prednisone and ‘untreated’
groups. Diplopia was present at the last exam in 27% of prednisone-treated (mean 7.2
years) and in 57% of ‘untreated’ (mean 4.6 years) OMG patients. For 48 prednisonetreated patients who did not develop GMG, OMG treatment failure occurred in 13.
Conclusions: Prednisone delays the onset of GMG and has sustained benefit of
reducing the incidence of GMG and controlling diplopia. Without prednisone, GMG
develops in 50% of OMG patients, typically within 1 year.
CR: M. Kurli, None; M.J. Kupersmith, None.
Support: : Alice and Richard Netter, David B. Kriser Foundation, and Michael Fisher
Foundation
Purpose: To determine the effect of transcorneal electrical stimulation(TES) on the
visual acuity of patients with traumatic optic neuropathy (TON).
Methods: Consecutive twenty-six eyes of 26 patients with TON treated by TES in
our hospital between 2004 and 2007 and were followed-up at least 2 months after the
treatment were studied. We classified the patients into three groups by the visual acuity
before treatment. Severe group, log minimum angle of resolution (logMAR)≥2, n=7,
moderate group, 1≤logMAR<2, n=10, and mild group, logMAR<1, n=9. TES (650-1000
μA, 20 Hz, 30 minutes) was applied using a contact lens-type stimulating electrode.
Followed-up period was 2 to 21 months (average, 7.1 months) We measured the visual
acuity, the threshold current to evoke phosphene in the peripheral visual field (Th1),and
the current to evoke phosphene in the central visual field (Th2).
Results: The visual acuity improved equal or more than 0.3 logMAR units in 10 patients
(1 in severe group. 6 in moderate group. 3 in mild group). The visual acuity did not
worsen more than 0.3 logMAR units in any of the patients. Except for the severe group,
visual acuity was significantly improved. (P=0.01 in moderate group and p=0.03 in
mild group, Signed Rank Test). Th1 was significantly improved except for the severe
group (P=0.01 in moderate group and p=0.03 in mild group). Threshhold of the central
phosphene was significantly improved only in the mild group (p=0.016) . No side effect
was observed except for a mild superficial keratopathy after TES.
Conclusions: The visual acuity and the threshold current to evoke phosphene
improved after TES in some patients with TON without major complications. The
treatment effect may not be expected in severely injured cases (logMAR≥2). These
results suggest that TES could be considered as a new treatment for eyes with mild
to moderate TON.
CR: H. Shimojyo, None; T. Fujikado, None; T. Morimoto, None; Y. Okawa, None; K.
Matsushita, None; Y. Kitaguti, None; Y. Tano, None.
Support: None
1438 - A328
Training Hemianopes in Their Blind Hemifield: Comparison of Two Left
Hemianopes on Detection and Categorisation Tasks
1439 - A329
Visual Outcomes of Patients With Neuromyelitis Optica While Receiving
Rituximab vs. Standard Treatment
I. Gaudry1A, C. Cavezian1A, C. Perez1A, M. Obadia1B, O. Gout1B, S. Chokron1A. AERT
TREAT Vision, BService de neurologie, 1Fondation Ophtalmologique Rothschild,
Paris, France.
M.S. Floyd, T.J. Whittaker. Ophthalmology, Kansas University Medical Center,
Overland Park, KS.
Purpose: Recovery from long lasting visual field defect after primary visual cortex
injury has scarcely been reported. Recently, Chokron et al. (2008) described an
enlargement of the visual field in adult hemianopes, after specialized rehabilitation
based on blindsight theories.
Methods: Following these same theories, we attempted to train high perceptual
processes in the blind field of two left hemianopes through “active training” (i.e., a
same/different judgement of two successive natural scene images, with feedback).
RP had minimal sparing in his upper left visual field. ML had upper left minimal
sparing on his right eye and lower-left minimal sparing on his left eye. As a control
task, a “passive training” (i.e., colour frame judgement in the central visual field)
was completed with a one-week delay from the active training. Training effects were
evaluated in a categorization task of natural scene images and in a detection task of
flashing dots. Both tasks were performed as pre- and post-training tests. In all tasks,
stimuli were presented centrally or with a 3.5° eccentricity, and fixation was controlled
with a video camera. In addition, the hemianopes performances were compared with
10 healthy controls.
Results: The “active training” increased detection rates in the blind hemifield of
both patients and showed slightly improved performance in the central-left visual
field. Moreover patient ML showed higher detection rates for stimuli presented in
the lower-left visual field but a lower detection rate for stimuli in the lower-right
visual field. Patients performed similar to controls for upper left presentations.
There was no improvement in categorization skills. Passive training did not lead
to improvements.
Conclusion: Although each training type was performed only once, detection
capacities seem partially flexible in some patients. Compared to automated perimetry
measures, our data suggest that attentional mechanisms could be redirected toward
one hemifield in hemianopia.
CR: I. Gaudry, None; C. Cavezian, None; C. Perez, None; M. Obadia, None; O. Gout,
None; S. Chokron, None.
Support: None
Purpose: To compare the visual outcome of patients with Devic’s Disease who undergo
treatment with Rituximab vs. other immune modulating treatment.
Methods: A retrospective chart review was conducted on 12 eyes (6 patients) with
Neuromyelitis Optica treated at Kansas University Medical Center. Patients were
diagnosed by NMO IgG antibodies, or clinical history, examination, and imaging.
Patients with multiple sclerosis, tumor, and cerebral vascular disease were excluded.
Visual acuity and Humphrey visual fields at the initial visit, 1 month, 3 to 6 months, and
1 year were collected. Data recorded during relapses was avoided due to inconsistency.
Medical treatment, relapse, and symptoms were documented. A statistically significant
change in acuity was defined as 3 Snellen lines and visual field greater than 2 db.
Results: Charts were reviewed from 2000 to 2008. The age range was 38 to 58. All
patients except 1 were followed for at least 3 months. This patient had recently enrolled
and is still being evaluated. 3 patients were diagnosed by NMO IgG and 3 clinically.
All patients were treated initially with steroids. 1 patient was treated with only
steroids, 1 with only rituximab, and 4 with other immune modulating drugs such as
mycophenolate moxetil, methotrexate, and plaquenil (2 of these were then switched to
rituximab). Visual acuity was stable at 1 year in 2 of 3 rituximab patients. One patient
receiving Rituximab who experienced visual decline was experiencing loss prior to
therapy. 2 of 3 patients in the non-Rituximab treatment group had a decline in acuity.
The following is a list of complications: leg and arm dysarthria and paresthesia, urine
retention, nausea, neck pain, and hospitalization. There were 24 relapses reported with
an average of 1.7 per year. 79 % of episodes occurred during the spring and fall.
Conclusions: Data from these patients indicate that Rituximab may be more effective
than steroids and immune modulating drugs in treatment of visual acuity and visual
field loss. There is no definitive trend regarding relapse rate between the groups.
There may be a correlation between relapse and seasonal changes. This is a difficult
group to study as medical records are imperfect because patients follow with multiple
specialties and data is often obtained when the patient is having a relapse. These
patients need to be followed for a longer duration and a larger sample size would
be optimal.
CR: M.S. Floyd, None; T.J. Whittaker, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1436-1439
Monday, May 4, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 1436 - 1447 / A326 - A337
222. Neuro-Ophthalmology: Treatment Organizing Section: EY
1440 - A330
Idebenone Treatment in Patients With Leber Hereditary Optic Neuropathy
1441 - A331
Long Term Follow-Up of Optic Nerve Sheath Decompression in Idiopathic
Intracranial Hypertension
J.G. Eng1,2, D. Aggarwal2, A.A. Sadun2. 1Department of Ophthalmology, University
of South Carolina, Columbia, SC; 2Doheny Eye Institute/USC Keck School of
Medicine, Los Angeles, CA.
Purpose: To examine whether patients with Leber Hereditary Optic Neuropathy (LHON)
may show improvement in vision after starting idebenone, a synthetic analog of Coenzyme
Q10.
Methods: 7 patients (6 males and 1 female) who took idebenone for LHON were selected
for this study. Four patients had the 11778 mutation; one patient had the 3460 mutation; one
patient had the 14484 mutation; the remaining patient had no mutation identified. These
patients had visited the neuro-ophthalmology clinic at Doheny Eye Institute from 2003 to
2008. Charts were reviewed and evaluated for any improvement in visual acuity (VA), color
vision, and Humphrey visual field after initiation of idebenone therapy.
Results: Four patients experienced no improvement in visual acuity, color vision, or
visual fields after taking idebenone. Three patients demonstrated a dramatic or marked
improvement. A 50 year old female with the 11778 mutation had VA of 20/200 OU when
starting idebenone 450 mg/day. VA improved to 20/50 OU in one month. When VA decreased
to 20/400 OD and CF 2 ft OS three months later, idebenone was increased to 540 mg/day. At
a follow-up visit six months later, VA had improved to 20/30 OD and 20/60 OS and visual
fields showed complete clearing of central scotomas. Her color vision also improved from
discerning 0/12 color plates OU prior to taking idebenone to 2/12 color plates OU. A 16 year
old male with the 14484 mutation had progressive visual loss with VA 4/200 OD and 5/200
OS, bilateral central visual field defects, and color vision of 0/8 OD and 3/8 OS using AO
test plates. He was started on idebenone 360 mg/day and over the course of 1.5 years, VA
improved to 20/40 OD and 20/60 OS. Visual fields showed improvement in both eyes with
a decrease in central depression OD and only a patchy central defect with preserved vision
nasally OS. Patient could discern 8/14 plates OD and 6/14 plates OS. A 17 year old male
with the 11778 mutation had VA of CF 4 ft OD and 20/400 OS and color vision of 0/8 plates
OD and 4/8 plates OS. He was started on idebenone 360 mg/day and after two months, he
experienced a modest improvement in VA OD to 20/200 with VA of 20/400 OS. He could
also discern 9/20 OD and 8/20 OS H-R-R plates after 2 months of idebenone. This patient
also experienced an improvement in his visual field.
Conclusions: Some patients with LHON treated with idebenone showed marked improvement
in visual acuity, color vision, and visual fields. Although prospective studies are needed to
determine the role of idebenone in visual recovery, the relatively safe side effect profile of
idebenone makes it a treatment option for many patients diagnosed with LHON.
CR: J.G. Eng, None; D. Aggarwal, None; A.A. Sadun, None.
Support: International Foundation for Optic Nerve Disease, Research to Prevent
Blindness
J.R. Shipp1, J. Corbett1, S. Kedar1, C. Willen2, M. Acierno3. 1Ophthalmology, University
of Mississippi, Jackson, MS; 2Ophthalmology, University of Alabama, Birmingham,
AL; 3Ophthalmology, Louisiana State University, New Orleans, LA.
Purpose: To evaluate the long term visual outcomes of subjects having undergone
optic nerve sheath decompression for the treatment of idiopathic intracranial
hypertension.
Methods: A retrospective chart review was performed on all patients who had
undergone optic nerve sheath decompression between October 1994 and April 2006
at the University of Mississippi Medical Center and the University of AlabamaBirmingham Hospital. Surgeries performed for diagnoses other than IIH were
excluded. Best-corrected visual acuity, color vision, optic disc appearance, and
automated perimetry were recorded for the pre-operative period and each postoperative visit through January 2008.
Results: We reviewed 100 cases of optic nerve sheath decompression in 75 patients.
We categoried our findings into 3 groups based on the level of pre-operative visual
acuity: (1) VA > 20/40 (2) VA = 20/50-20/200 (3) VA < 20/200. Of the 49 eyes in group 1,
43 eyes (88%) had a final visual acuity of 20/40 or better, 4 eyes (8%) had a final visual
acuity of 20/50-20/200, and 2 eyes (4%) had a final visual acuity of less than 20/200.
Of the 29 eyes in group 2, 10 eyes (34%) had a final visual acuity of 20/40 or better, 15
eyes (52%) had a final visual acuity of 20/50-20/200, and 4 eyes (14%) had a final visual
acuity of less than 20/200. Of the 22 eyes in group 3, 2 eyes (9%) had a final visual acuity
of 20/40 or better, 1 eyes (5%) had a final visual acuity of 20/50-20/200, and 19 eyes
(86%) had a final visual acuity of less than 20/200. Of all cases taken together, 81 eyes
(81%) showed improvement or stabilization of their visual acuity. Mean and pattern
standard deviations on automated perimetry showed a trend toward improvement,
color vision remained stable, and disc appearance evolved from edematous (96%)
initially to pallor (58%) at final visit.
Conclusions: Optic nerve sheath decompression in the treatment of idiopathic
intracranial hypertension tends to stabilize patients in the long term. Visual prognosis
is better in patients with good visual acuities initially. Patients with poor visual acuities
initially tended to retain poor visual acuities. Consideration should be given to earlier
surgical intervention in IIH before visual acuity is signicantly affected.
CR: J.R. Shipp, None; J. Corbett, None; S. Kedar, None; C. Willen, None; M. Acierno,
None.
Support: None
1442 - A332
Optic Nerve Sheath Fenestration With a Raman-Shifted Mid-Infrared Laser
(Tissue Study)
1443 - A333
Long-Term Outcomes for the Mouse Eye with AAV Mediated Gene Delivery of
the Human ND4 Complex I Subunit
J. Shen1A, J. Kozub1B, R. Prasad1A, K. Joos1A. AOphthalmology, BFree Electron Laser
Center, 1Vanderbilt University, Nashville, TN.
X. Qi1A, A. Lewin1B, W. Hauswirth1A, J. Guy2. AOphthalmology, BMolecular Genetics
and Microbiology, 1University of Florida, Gainesville, FL; 2Ophthalmology,
University of Miami, Miami, FL.
Purpose: Optic nerve sheath fenestration is a treatment for vision loss in idiopathic
intracranial hypertension not responding to medical management. Our previous
studies suggest that endoscopic application with Free Electron Laser energy at 6.1
μm may be useful for minimally invasive orbital therapy including optic nerve
sheath fenestration. This study proposes to make this technique more clinically
feasible with substitution of a portable laser for the cost-prohibitive experimental
Free Electron Laser (FEL).
Methods: The laser proposed for this study is a Q-switched, tunable alexandrite
laser system, which provides a high-intensity, Q-switched output pulse of 50-100
ns at 10 pulses per second (Light Age, Inc.). It is wavelength-shifted by a two-stage
stimulated Raman conversion process into the 6-7 μm range. Ten fresh cadaver porcine
optic nerves were lased with 6.1 μm at 0.6 mJ with a 100 μm diameter spot. Besides
linear incisions, a circular pattern was cut and the incised piece removed to form
an optic nerve sheath window. Specimens were examined grossly and prepared for
histological examination.
Results: The table-top laser has a nearly Gaussian output and a narrow spectrum at
6.1 μm. The laser was capable of continuously incising the cadaver porcine optic nerve
sheaths. Minimal thermal damage was evident.
Conclusions: A Q-switched, Raman-shifted tunable alexandrite laser system is
capable of providing the parameters necessary for incision of an optic nerve sheath.
This portable system will provide the translational advancement necessary to bring
endoscopic laser surgery closer to clinical usefulness.
CR: J. Shen, None; J. Kozub, None; R. Prasad, None; K. Joos, None.
Support: AFSOR – DOD FA9550-04-1-0045, NEI Core Grant EY08126-18, Unrestricted
Departmental Grant from Research to Prevent Blindness, Inc., NY; Joseph Ellis Family
Research Fund.
Purpose: To evaluate the long-term effects of AAV mediated allotopic gene expression of a
normal human ND4 (wt-ND4) of complex I subunit in the mouse visual system.
Methods: wt-ND4 was made compatible with the universal genetic code and a mitochondrial
targeting sequence (ATPc) was appended to the N terminus and an epitope (FLAG) added to
the C terminus. This construct was packaged into AAV2 capsids. AAV containing wt-ND4,
mutant (R340H) ND4 (mut-ND4), and GFP were intravitreously injected into the mice eyes.
One year later, gene expression and potential toxicities were assessed by fluorescence, light
and electron microscopy.
Results: One year after the gene inoculation fluorescence microscopy revealed 15.0% FLAG
positive and 5.3% GFP-positive retinal ganglion cells (RGC) in flat mounted retina of AAVwt-ND4 injected eyes, relative to the mean number of RGCs. The level of AAV-mut-ND4 gene
expression was similar that the FLAG positive RGCs was 16.0% and GFP-positive RGCs was
5.4%. AAV- wt-ND4 inoculated retina had mean RGC of 3100+142 cells/mm 2, a 3.5 % less
than the normal untreated eyes with mean of 3314+138 cells/mm 2, p>0.05. In contrast, AAVmut-ND4 caused 40% loss of RGC with mean of 1956+143 cells/mm 2, p<0.01. Morophometric
analysis revealed that AAV-GFP inoculation caused 7% bigger in area of optic nerve head
(ONH) relative to normal eyes, p>0.05. AAV-wt-ND4 gene inoculation showed the ONH
swelling by 14%, p>0.05. AAV-mut-ND4 inoculation caused optic head swelling by 30 %,
p<0.05. In the retrobulbar optic nerve cellular infiltration was increased almost two-fold (p
< 0.01) in mut-ND4 treated eyes as compared to normal eyes. Delivery of the AAV- wtND4 or
GFP did not change the cellular infiltration. To detect any demyelination in the retrobulbar
optic nerve, the area of axonal myelin fiber was measured. As compared to normal eyes,
AAV- wtND4 or GFP decreased the area of axonal myelin fiber by 3-5%, both p>0.05. The
mut-ND4 inoculation caused axonal myelin fiber thinner by 36% (p<0.01), meaning the loss of
myelin. Counting the number of axons, in contrast to the normal untreated eyes, AAV-GFP or
wt-ND4 decreased the axons by 5% or 9%, respectively, both p>0.05. The severe loss of axons
was evident after mut-ND4 gene inoculation, caused 41% loss of axons (p<0.01).
Conclusions: A nuclear-encoded, importable version of wt-ND4 delivered by AAV2 can
be detected one year after gene transfer. Expression of normal human ND4 in murine did
not induce significant loss of RGCs and the axonal demyelination suggesting it may safe
for treatment of LHON.
CR: X. Qi, None; A. Lewin, None; W. Hauswirth, None; J. Guy, None.
Support: RO1EY017141, Department RPB
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1440-1443
Monday, May 4, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 1436 - 1447 / A326 - A337
222. Neuro-Ophthalmology: Treatment Organizing Section: EY
1444 - A334
Restoration of Electroretinogram Activity in Exenterated Swine Eyes Following
Ophthalmic Artery Anastomosis
D. Ellenberg, J. Shi, H. Qian, S. Jain, J.-H. Chang, D.T. Azar. Ophthalmology,
University of Illinois at Chicago (UIC), Chicago, IL.
1445 - A335
Effects of Corticosteroids in Experimental Optic Neuritis
M. Dutt1, P. Tabuena2, E. Ventura2, A. Rostami2, K. Shindler1. 1Ophthalmology,
University of Pennsylvania, Philadelphia,, PA; 2Neurology, Thomas Jefferson
University, Philadelphia,, PA.
Purpose: To determine the feasibility of restoring electroretinogram (ERG) activity
of exenterated swine eyes following in vivo arterial anastomosis.
Methods: The carotid artery was exposed and cannulated. The eye was exenterated
along with the extraocular muscles and surrounding connective tissue. The ophthalmic
artery was then identified and anastomosed to the carotid artery. Perfusion was
confirmed by injecting FITC-conjugated tomato lectin into the anastomotic tubing and
performing confocal microscopy of retinal flat-mounts. Dark-adapted ERG and optic
nerve responses were analyzed to assess retinal function, and dilated eye examination
and retinal imaging were performed.
Results: Arterial anastomosis resulted in perfusion of blood from the carotid artery
through the anastomosis and into the ophthalmic artery. Arterial perfusion was
confirmed by the presence of tomato lectin-stained retinal vessels. Immediately
following the anastomosis, ERG and optic nerve activity was minimal. However, an
“a” wave (representing photoreceptor activity), “b” wave (representing bipolar cell
activity), and optic nerve responses (representing RGC activity) were detected at 30
min after reperfusion.
Conclusions: Electroretinographic function is restored following re-anastomosis of
exenterated swine eyes.
CR: D. Ellenberg, None; J. Shi, None; H. Qian, None; S. Jain, None; J.-H. Chang,
None; D.T. Azar, None.
Support: Supported by NIH P30-001792 (DTA) and an unrestricted departmental
support from Research to Prevent Blindness (New York, NY)
Purpose: Optic neuritis (ON) occurs with a high incidence in experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). ON begins 9
days after immunization to induce EAE. Significant retinal ganglion cell (RGC)
loss occurs in eyes with ON and is not detected until 14 days after immunization,
suggesting that loss of RGCs is secondary to optic nerve inflammation. Treatment
with corticosteroids suppresses RGC loss if administered daily beginning from day
of immunization (d0) prior to disease onset. Our aim was to determine whether
corticosteroid treatment is also effective at a clinically relevant time point after
inflammation of the optic nerve begins.
Methods: Stereotactic surgery with Fluorogold was used to retrogradely label RGCs.
Proteolipid protein peptide 139-151 was injected to induce EAE and mice were scored
daily for clinical EAE on a 5 point scale. Mice were treated daily from d0 to d14 or d10
to d14 with 200 mg/kg subcutaneous dexamethasone (dex), 20 mg/kg intraperitoneal
methylprednisolone (MP) or PBS (control). Fluorescence microscopy was used to count
labeled RGCs in retinal mounts and H&E staining was used to identify inflammatory
infiltrates in the optic nerves.
Results: Corticosteroid treatment from d0 to d14 almost completely blocked EAE,
where PBS-treated mice developed typical EAE with an average score of 1.5 by d14.
Less than 5% of eyes had ON when treated with dex from d0-d14 compared to more
than 60% when treated with PBS and dex-treated eyes had significantly increased
(>30%) RGC survival. Treatment with either dex or MP from d10-d14 led to only
partial suppression of clinical EAE. Corticosteroid treatment beginning from d10
did not significantly reduce the presence of optic nerve inflammation at d14 or 18,
nor did it enhance survival of RGCs.
Conclusions: These experiments indicate that corticosteroid treatment in EAE mice
initiated after inflammation has begun is not as effective when administered before
the onset of ON. This is consistent with clinical outcomes in ON patients where MP
treatment does not affect final visual outcome. This model can be used to evaluate
potential alternative therapies to prevent RGC loss and permanent vision loss from
ON.
CR: M. Dutt, None; P. Tabuena, None; E. Ventura, None; A. Rostami, None; K.
Shindler, None.
Support: NIH/ NEI grant no. KO8EY15098, Career Development Award from RPB,
F.M. Kirby Foundation
1446 - A336
Involvement of Trx1 in Protective Effect of 17β-Estradiol Against TNF-αInduced Axonal and Cell Body Degeneration
1447 - A337
Neuroprotective Effect of Ciliary Neurotrophic Factor (CNTF) in a Rodent
Model of Nonarteritic Anterior Ischemic Optic Neuropathy
Y. Kitaoka, Y. Munemasa, Y. Hayashi, S. Ueno. Ophthalmology, St Marianna
University School of Med, Kawasaki, Japan.
M.K. Mathews1, A. Hunter, III 2, S.L. Bernstein1. 1Ophthalmology, University
of Maryland, Baltimore, MD; 2Ophthalmology, University of Pennsylvania,
Philadelphia, PA.
Purpose: To examine the effect of 17β-estradiol (E2) on the level of Trx1 in TNF-αinduced optic nerve degeneration. To evaluate the role of Trx1 in protective effect of
E2 on RGC-5 cell death induced by TNF-α.
Methods: Eight-week-old female Wistar rats were divided into sham operated and
ovariectomized (OVX) groups. The OVX rats were treated with either solvent vehicle
or E2 subcutaneous implant immediately after ovariectomy. At 14 days post-operation,
all rats were received intravitreal injection of 10 ng TNF-α or PBS. The eyes were
enucleated 1, 7, or 14 days after intravitreal injection. Furthermore, RGC-5 cell (gift
from N. Agarwal) viability was tested after exposure to 10, 50, or 100ng/ml TNF-α
with or without glutamate. The effects of E2 (1 or 10 μM) and Trx1 siRNA were also
evaluated. The expression of Trx1 in optic nerve or RGC-5 cells was examined by
Western blot analysis. The localization of Trx1 in optic nerve cross section as well as
transverse section was evaluated by immunohistochemistry.
Results: Immunohistochemistry showed the substantial co-localization of Trx1 and
neurofilament in the optic nerve. Morphometric analysis showed that E2 implantation
significantly ameliorated TNF-α-induced axon loss. The level of Trx1 in the optic nerve
was increased with E2 implantation. Cell viability assay showed that E2 treatment
significantly improved the death of RGC-5 cells induced by TNF-α and glutamate.
This ameliorated effect was significantly inhibited by Trx1 siRNA transfection. The
level of Trx1 in the RGC-5 cell was significantly increased with E2 treatment and this
increase was ameliorated by Trx1 siRNA.
Conclusions: E2 can exert axonal and cell body protection against TNF-α-induced
neurodegeneration with possible involvement of Trx1.
CR: Y. Kitaoka, None; Y. Munemasa, None; Y. Hayashi, None; S. Ueno, None.
Support: This work was supported by Grant-in-Aid No. 20791285 (YK) from the
Ministry of Education, Culture, Sports, Science, and Technology of the Japanese
Government; Uehara Memorial Foundation
Purpose: To determine whether Ciliary Neurotrophic Factor (CNTF) exerts a
neuroprotective effect in a mouse model of Anterior Ischemic Optic Neuropathy
(AION) - rodent-AION (rAION).
Methods: Male transgenic mice with the Thy-1 promoter, linked to cyan fluorescent
protein (CFP) reporter ((Thy-1 (CFP) mice), (28-44g) were anesthetized, and AION was
induced using a previously described experimental method - rodent AION (rAION)
(1). Then one eye of each animal received an intravitreal injection of 0.75μg Ciliary
Neurotrophic Factor (CNTF), which has been widely shown to protect retinal ganglion
cells after injury (2). Controls included both sham-injected and untreated animals.
Sham-injections consisted of 0.01 ml PBS intravitreally. On day 14, the animals were
sacrificed by Co2- anesthesia and subsequent cervical dislocation; Eyes were enucleated,
and fixed in 4% paraformaldehyde-PBS. Anterior chambers were removed; The retina
was dissected out of the eye cup and mounted on microscope slides. CFP- fluorescent
retinal ganglion cells (RGC’s) were imaged using confocal microscopy. The amount of
RGC loss was determined by averaging the number of RGC’s counted in 12 randomly
selected 200μ2 fields in each retina (400x magnification). Average RGC numbers and
standard deviations were calculated using the Student’s t-test. The percentage of lost
RGC’s was calculated for each treatment group.
Results: After rAION induction, eyes treated with PBS only lost 55.7% of RGC’s when
compared to controls. The CNTF- treated eyes lost an average of 36.8% of RGC’s when
compared to controls. Therfore, CNTF injection resulted in an 18.9% decrease of RGC
loss, when compared to PBS after rAION induction.
Conclusions: The rodent model of AION and neuroprotection mimicks the actual
clinical events in AION by selectively targeting the vasculature of the optic nerve
head. Introduction of the neuroprotective factor after the ischemic event models the
sequence of clinical disease followed by intervention more accurately than if CNTF
were introduced in the eye before induction of ischemia. Preliminary data indicate
that CNTF exerts a neuroprotective effect in sudden optic nerve ischemia. This model
enables evaluation of neuroprotective factors in clinical post-stroke treatment in
ischemic optic neuropathy.
References:
1. Goldberg-Cohen, N Guo Y, et al. IOVS 2005; 46: 2716-2725
2. Mey J, Thanos S. Brain Res. 1993; 602: 304-317
CR: M.K. Mathews, None; A. Hunter, III, None; S.L. Bernstein, None.
Support: NIH Grant EY015304 (SLB)
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1444-1447
Monday, May 4, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 1979 - 1998 / D754 - D773
264. Strabismus II Organizing Section: EY
1979 - D754
Clinical Application of a Digital Head Posture Measuring System for Pediatric
Patients
E.S. Hald1A, R.W. Hertle1B, D. Yang1B. AOphthalmology/Bioengineering,
B
Ophthalmology, 1University of Pittsburgh, Pittsburgh, PA.
1980 - D755
Sensitivity Analysis for Strabismus Measurements Using Corneal Reflections
E.B. Geukers1, S. Schutte1, P.P. Jonker1, B.A.J. Lenseigne1, F.C.T. van der Helm1, H.J.
Simonsz2. 1Biomechanical Engineering, TU Delft, Delft, Netherlands; 2Erasmus
Medical Center, Rotterdam, Netherlands.
Purpose: We have developed a digital head posture measuring system (DHP) and
previously reported its validity tested with an artificial head and normal subjects in
3D positions (Yang, et. al 2007, Hald, et. al 2008). Now, we report its repeatability and
accuracy of measurements performed in pediatric patients.
Methods: All testing was performed with IRB approval. The DHP consists of a headmounted electronic compass, a standard PC, and customized software to sample
and display 3D head posture in real time. It is mounted on a wire frame, similar to
eyeglass frames. For repeatability tests (10 subjects), patient was instructed to view
an image at a distance of 170 mm. The device was calibrated to zero when the patient
reached their anomalous head posture. The patient’s head was then manually moved
to the true zero position in 3D space by the investigator, and values for simultaneous
yaw, pitch, and roll were sampled. Accuracy tests (5 subjects) involved the same basic
procedure as repeatability tests but included the addition of a manual head posture
measuring device (MHP) to calculate actual angle of measurement for statistical
comparison (Yang, et. al 2007, Hald, et. al 2008). Repeatability values were found for
repeatability tests and accuracy data were analyzed using a matched paired t-test to
determine if differences between MHP and DHP angles are significant.
Results: The DHP showed consistent outcomes compared with the MHP. Four subjects
displayed pitch head postures, five displayed yaw head postures, and one displayed
roll head postures. Match pairs t-tests for the difference between MHP and DHP head
posture angles showed no significant difference between MHP and DHP angles for
pitch, yaw and roll head postures (p > 0.05 for all three). Seven of the repeatability test
subjects displayed noticeable yaw head postures, two displayed pitch head postures
and three displayed roll head postures. After removing high and low angles from
each subject’s data set, pitch subjects yielded 95% repeatability values ranging from
6-14 degrees. Yaw and roll subjects yielded repeatability values ranging from 3-23
degrees and 4-17 degrees, respectively.
Conclusion: The repeatability and accuracy of the measurements with DHP was
supportive for the use of the DHP on pediatric patients. With additional patient
testing and improvement of measurement procedures, the DHP will be a valid device
to repeatedly measure head posture in 3D.
CR: E.S. Hald, None; R.W. Hertle, None; D. Yang, None.
Support: Fight For Sight Summer Studentship
Purpose: The reoperation rate of strabismus surgery is about 20%. The main
determinant for the amount of muscle relocation is the preoperative angle of
strabismus. Currently, the Prism Cover Test (PCT) is the golden standard to measure
strabismus angles. Drawbacks of PCT include the limited precision, the required time
and required cooperation level. Accordingly, there is potential for a more accurate
and quicker strabismus measurement device. A potential principle for this device
is the IR eye tracking technique of measuring the corneal reflection relative to the
corneal center.
Methods: The sensitivity of the method of measuring angles of strabismus using
the corneal reflection relative to the corneal center was investigated in relation to a
patient’s biometric parameters and the geometry of the measurement setup. A 2D
model was made of the setup and the anatomy of the eye according to Gullstrand’s
eye model (Le Grand and El Hage, 1980). The sensitivity of the measurement method
to variations (mean ± 2SD) in the corneal radius (Rc), the anterior chamber depth
(ACD), the interpupillary distance (IPD) and the distance (d) and rotation (α) of the
head with respect to the experimental setup were investigated.
Results: Strabismus angles were determined theoretically using relative distances
between the calculated corneal reflection and corneal center in the 2D model. The
corneal reflection method was sensitive to Rc (± 5% for 7.8 ± 0.6mm), ACD (± 16% for
3.2 ± 0.8mm) and to head rotation α (± 4% for 0 ± 10°). Measurement accuracy was
affected little by the head distance d (± 0.2% for 1000 ± 100 mm) and IPD (± 0.1% for
60 ± 20 mm).
Conclusions: In a strabismus measurement device, the patient’s Rc, ACD and head
rotation with respect to the camera should be accounted for, as these parameters have
a significant influence on the measurement accuracy. The IPD and the head distance
from the patient to the experimental setup can be neglected.
CR: E.B. Geukers, None; S. Schutte, None; P.P. Jonker, None; B.A.J. Lenseigne,
None; F.C.T. van der Helm, None; H.J. Simonsz, None.
Support: None
1981 - D756
Graves Ophthalmopathy - Predictors of Diplopia
1982 - D757
Binocular Interactions in Human Strabismus: A Multifocal VEP Study
W.E. Adams1, H. Haggerty2, J. Dickinson2, A. Coulthard 3. 1Ophthalmology, Sunderland
Eye Infirmary, Sunderland, United Kingdom; 2Ophthalmology, Royal Victoria
Infirmary, Newcastle Upon Tyne, United Kingdom; 3Radiology, Royal Brisbane and
Women’s Hospital, Brisbane, Australia.
H. Cheng, B. Zhang, K. Wicks, Y. Chino. College of Optometry, University of Houston,
Houston, TX.
Purpose: Patients with Graves Ophthalmopathy (GO) frequently experience diplopia
due to restrictive myopathy. Some investigators have suggested that the MRI
measurements of extraocular muscle volume can be used to predict ocular motility
and diplopia. We compared muscle volumes and uniocular fields of fixation (UFOF)
to the field of binocular single vision (BSV).
Methods: 24 patients with GO were evaluated by plotting a field of BSV on the
Goldmann perimeter and scored from 0 (constant diplopia) to 100 (no diplopia).
UFOF were plotted for each eye along 6 muscle axes. Muscle volumes were measured
from 3-D MRI images. UFOF measurements and muscle volumes were compared
between the 12 patients with significant diplopia (BSV score <80) and the 12 without
significant diplopia (BSV>80).
Results: The patients with diplopia had lower UFOF scores for 7 of 8 muscles compared
to those without diplopia (Right Medial Rectus 37.0 deg vs 48.2, R Lateral Rectus 32.1 vs
42.8, R Inferior Rectus 19.9 vs 32.5, R Superior Rectus 44.7 vs 55.5, Left Medial Rectus
37.9 vs 47.7, L Lateral Rectus 34.3 vs 43.3, L Inferior Rectus 25.1 vs 33.9, p < 0.01 for all
comparisons). Only the UFOF of the LSR was borderline significantly different (47.6 deg
vs 54.7, p=0.06). In contrast, individual muscle volumes (mm3 ) although numerically
larger in patients with severe diplopia, were statistically similar (RMR 938.8 vs 836.8,
RLR 809.4 vs 705.8, RIR 1050.3 vs 948.9, RSR 1185.8 vs 874.2, LMR 1066.6 vs 895.8, LLR
788.3 vs 672.6, LIR 1078.0 vs 846.5, LSR 1182.3 vs 874.3, all comparisons p>0.05). Total
muscle volumes and total orbital volumes were also similar (8075.5 +/- 2632.7 vs 6671.2
+/- 1904.9, p= 0.1 and 41298.3 +/- 9140.9 vs 37405.3 +/- 8776.0, p=0.3 respectively).
Conclusions: Diplopia in GO is strongly associated with reductions of individual
muscle ductions, but this association is not paralleled by significant differences in
muscle volumes. MRI cannot be used to predict motility and diplopia, and restriction
should be assessed by clinical methods such as UFOF and BSV.
CR: W.E. Adams, None; H. Haggerty, None; J. Dickinson, None; A. Coulthard,
None.
Support: None
Purpose: To study the characteristics of binocular interactions in human
strabismus
Methods: MfVEPs were recorded in 17 normal and 8 strabismic subjects with a
60-sector pattern-reversal dartboard stimulus (VERIS). Normal subjects were tested
under 3 viewing conditions: 1) monocular 2) bi-foveal and 3) diplopic. Strabismic
subjects were tested under conditions 1) and 2), and their natural viewing condition.
A haploscope coupled with an alternating cover test was used to achieve bi-foveal or
diplopic conditions. Response amplitude (amp) was the root-mean-square amplitude
in the signal window. Binocular interaction was assessed by a binocular-monocular
ratio (BMR) averaged over 60 sectors, and BMR for each sector was the ratio of a
sector’s amp under two-eye viewing condition to the better monocular amp at that
sector, and expressed in dB.
Results: Normal subjects showed binocular summation (BMR>0) under bi-foveal
condition and binocular inhibition (BMR<0) under diplopic condition for all
eccentricities with a mean BMR±SD of 0.47±0.46 dB and -1.47±0.74 dB, respectively.
All strabismic subjects tested under natural viewing condition and 7 under bi-foveal
condition reported single vision (presumably due to clinical suppression), and no
binocular inhibition was observed for bi-foveal (mean BMR: 0.82±0.60 dB) or natural
viewing (mean BMR: 1.07±0.61 dB) conditions. One subject couldn’t achieve bi-foveal
viewing due to horror fusionis. He noted diplopia when targets were brought as close
as possible to his foveas and showed inhibition under this condition (BMR = -1.21 dB).
Another strabismic subject could see single or double under natural viewing condition.
Her BMR was 1.03 dB and -0.64 dB under single and diplopic conditions.
Conclusions: At the onset of strabismus (hence diplopia), V1 cortical physiology is
likely to be dominated by inhibitory binocular interactions. However, since binocular
inhibition could be demonstrated in our strabismic (and normal) subjects only under
diplopic conditions and mfVEP signals are known to largely reflect the activity of V1
neurons, the neural mechanisms underlying clinical suppression in strabismic humans
appear to reside beyond V1.
CR: H. Cheng, None; B. Zhang, None; K. Wicks, None; Y. Chino, None.
Support: NIH grants EY08128, P30 EY07551, T35EY0788, and Benedict-McFadden
Professorship to YC
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1979-1982
Monday, May 4, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 1979 - 1998 / D754 - D773
264. Strabismus II Organizing Section: EY
1983 - D758
Prevalence of Strabismus and Amblyopia in Singapore Chinese Children: The
Strabismus, Amblyopia and Refractive Error in Singaporean Children (STARS)
Study
M. Dirani1, A. Chia2, G. Gazzard 3, Y. Chan4, P. Selvaraj5, T.L. Young6, P. Mitchell7, T.Y. Wong1,
S. Saw5. 1Ophthalmology, Centre for Eye Research Australia, Melbourne, Australia;
2
Ophthalmology, Department of Ophthalmology, Singapore National Eye Center,
Singapore, Republic of Singapore, Singapore, Singapore; 3Ophthalmology, Glaucoma
Research Unit, Moorfields Eye Hospital, United Kingdom., Moorfields, United Kingdom;
4
Statistics, Yong Loo Lin School of Medicine, National University of Singapore,
Singapore, Singapore; 5Community, Occupational and Family Medicine, Department
of Community, Occupational and Family Medicine, National University of Singapore,
Singapore, Republic of Singapore, Singapore, Singapore; 6Ophthalmology, Department
of Ophthalmology, Duke University Medical Center, Durham, NC, Durham, NC;
7
Ophthalmology, Dept of Ophthalmology, University of Sydney, Australia., Sydney,
Australia.
Purpose: To determine the prevalence of strabismus and amblyopia in Singapore Chinese
children aged 6 to 72 months.
Methods: A population based survey was undertaken in the South-Western region of
Singapore. Disproportionate random sampling by 6 month age groups was performed.
Children underwent an Orthoptic assessment and cycloplegic (3 drops of cyclopentolate
at 5 minute intervals) refraction using a table-mounted autorefractor in children older
than 24 months, or a hand-held autorefractor in children aged 24 months or older, or streak
retinoscopy if autorefraction failed. LogMAR Visual acuity was tested in children aged 30
months or older. If amblyopia was suspected (two line difference in visual acuity), visual
acuity was re-tested.
Results: 3009 children were recruited (participation rate = 72.3%), of which 3004 were
analysed. The prevalence of strabismus in children (6 to 72 months) was 0.84% (95% Confidence
Interval, CI: 0.80%-1.19%). Prevalence increased from 0.56% to 0.96% between ages 6 to 36
months and 37 to 72 months, but this was not significant (p=0.23) and there were no gender
difference (p=0.54). Exotropia (20/24, 83.3%) was the most common strabismus, followed
by Esotropia (3/24, 12.5%). The prevalence of amblyopia in children aged between 30 to 72
months was 1.87% (95% CI 1.81-1.94). There were no significant age and gender differences
(p = 0.17). Amblyopia was attributed to refractive error alone in 72%, combined refraction/
strabismus in 23%, and strabismus alone in 5%. Refractive causes of amblyopia included
astigmatism (59%), high hyperopia (20%), and myopia (14%).
Conclusions: The prevalence of Strabismus and Amblyopia in preschool Singaporean
Chinese children was low. Exotropia was the most common strabismus and astigmatism
was the main determinant of amblyopia.
CR: M. Dirani, None; A. Chia, None; G. Gazzard, None; Y. Chan, None; P. Selvaraj,
None; T.L. Young, None; P. Mitchell, None; T.Y. Wong, None; S. Saw, None.
Support: None
1984 - D759
Defining the Critical Period for Eye Alignment Development in Infant Primates:
Effects of Binocular Decorrelation
K. Lam1, P. Foeller2, D. Bradley3, L. Tychsen2, A.M. Wong1. 1Faculty of Medicine,
University of Toronto, Toronto, ON, Canada; 2Department of Ophthalmology and
Visual Sciences, Washington University School of Medicine, St. Louis, MO; 3Yerkes
Regional Primate Research Center, Atlanta, GA.
Purpose: Earlier studies by our group have found that an optical strabismus induced
in non-human primates at birth causes a permanent large-angle esotropia when image
decorrelation occurs between the first 3-12 weeks of life (equivalent of age 3-12 months
in humans). The purpose of this study was to further delineate the critical period of
eye alignment development.
Methods: Binocular image decorrelation was imposed on 12 normal infant macaques
(Macaca mulatta) by fitting them with prism goggles on day 1 of life. The goggles were
removed after 3 (n=2), 6 (n=2), 9 (n=2), 12 (n=3), or 24 weeks (n=3), emulating surgical
repair of strabismus in humans at 3, 6, 9, 12, and 24 months of age, respectively. Two
monkeys wore plano lenses and served as controls. Several months after the goggles
were removed, eye alignment was recorded using binocular search coils during
automated single and alternate-cover testing. Alignment in each cardinal position
was measured during steady fixation to assess concomitance.
Results: The longer the duration of image decorrelation, the greater the magnitude
of resultant concomitant esotropia. Only physiological (< 2 deg) heterophorias were
detected in the control, 3-wk and 6-wk-duration groups. The 9-wk, 12-wk, and 24-wkduration monkeys exhibited larger-angle estropias (9 - 12 deg).
Conclusions: Longer durations of binocular decorrelation in infancy cause greater
maldevelopment of the vergence system manifested as larger-angle esotropia. Our
findings suggest that surgical repair in infantile esotropia in humans would be
most beneficial before the age of 6 months, and supports early correction of infantile
strabismus.
CR: K. Lam, None; P. Foeller, None; D. Bradley, None; L. Tychsen, None; A.M.
Wong, None.
Support: NIH EY10214, and Walt and Lilly Disney Award for Amblyopia Research
from Research to Prevent Blindness
1985 - D760
Functional MRI in Macaque Monkey With Infantile Strabismus: Nasotemporal
Motion Processing and Eye Tracking
1986 - D761
The Effect of Spectacle Wear on Health Related Quality of Life Measured Using
the Intermittent Exotropia Questionnaire
W. Bentley1A, L. Snyder1A, S. Petersen1B, P. Foeller1C, L. Tychsen1D. AAnatomy &
Neurobiology, BNeurology, COphthalmology & Visual Sciences, DOphthalmology
& Visual Sciences, Anatomy & Neurobiology, 1Washington University School of
Medicine, St. Louis, MO.
T. Yamada, S.R. Hatt, D.A. Leske, J.M. Holmes. Department of Ophthalmology, Mayo
Clinic, Rochester, MN.
Purpose: Binocular decorrelation in the first weeks of life produces the infantile
esotropia syndrome in infant primates. The animals possess all of the behavioral
features observed in strabismic children, including nasotemporal asymmetries of
motion processing and gaze (latent nystagmus, pursuit, OKN and ocular following).
The asymmetry is evident as a bias favoring nasalward motion. The goal of the
present study was to determine which gaze and motion processing brain areas are
more active for nasalward motion.
Methods: A pilot functional imaging study was conducted in an anesthetized primate
(age 2 yrs) who had infantile esotropia produced by 9 wks of prism goggle wear
(binocular decorrelation). Anesthesia was accomplished with isoflurane (1-1.5%), and
fMRI signals were recorded under conditions of dichoptic viewing using a surface
coil. Blood-oxygenation level dependent (BOLD) images were obtained with 1.5 mm
isotropic voxels and 2.25 mm of smoothing.
Results: Eight trials of each of 4 conditions were tested, nasalward motion (2
conditions: right eye viewing leftward motion and left eye viewing rightward motion)
vs. temporalward motion (2 conditions: right eye viewing rightward motion and left
eye viewing leftward motion). A statistical map of the differential activation was
derived and superimposed on a 3D reconstruction of the brain. Activation in the
superior temporal sulcus in the vicinity of MT and MST was significantly stronger
for nasalward compared to temporalward motion. The time course of the response
was a sharp uptick in the first seconds with an overshoot followed by a long shallow
downward ramp. Asymmetric activity (stronger for nasalward motion) was also
apparent in VIP and FEF.
Conclusions: These pilot data confirm that, in infantile esotropia, gaze-related
regions of the cerebral hemispheres show asymmetries in activation for nasalward
vs. temporalward visual motion. More data will be required to determine whether
the locations of the activation-asymmetry differ with subtype of tracking behavior
and to test hypotheses regarding other cortical and subcortical areas of interest
(e.g. NOT).
CR: W. Bentley, None; L. Snyder, None; S. Petersen, None; P. Foeller, None; L.
Tychsen, None.
Support: None
Purpose: To investigate the effect of spectacles on the health related quality of
life (HRQOL) of children and their parents using the new Intermittent Exotropia
Questionnaire (IXTQ) and the PedsQL questionnaire. We were specifically interested
in whether spectacle wear affected IXTQ scores.
Methods: We recruited 41 children, median age 8 years (range 5 to 13), presenting
with normal visual acuity (20/40 or better) and an otherwise normal eye examination
(specifically no strabismus), who either had no refractive error (n=28) or had refractive
error corrected with spectacles (n=13). One parent was recruited with each child. The
IXTQ and PedsQL were completed, each comprised of a Child survey (self-report by
child) and a Proxy survey (Child’s HRQOL from parent perspective). In addition,
the IXTQ contains a Parent survey (self-report of the parent’s own HRQOL). Each
questionnaire was scored from 0 (worst HRQOL) to 100 (best HRQOL). Median scores
were calculated for each group (spectacles vs. no spectacles) and compared using
Wilcoxon rank sum tests.
Results: Child IXTQ scores were similar between both groups (92 with spectacles
vs 90 without, P= 0.7) but Proxy IXTQ scores were lower for spectacle wearers (94 vs
100, P = 0.04). Proxy questions that scored lower in the spectacle group were related
to teasing and feeling different. Parent IXTQ scores were lower for spectacle wearers
(90 vs 97, P=0.002). Parent questions that scored lower in the spectacle group were
related to parental worry about vision, surgery, self consciousness, and teasing. In
contrast, for the PedsQL, composite scores and all subscale scores were similar between
spectacle wearers and non-spectacle wearers, both for Child surveys (composite 82
vs 84, P>0.7 for all comparisons) and Proxy surveys (composite 96 vs 94, P>0.2 for
all comparisons).
Conclusions: HRQOL, as perceived by the parent, was lower for children wearing
spectacles than that of children who did not wear spectacles using the Proxy IXTQ.
Parental worry about their children wearing spectacles was also apparent using the
Parent IXTQ questionnaire. Future uses of the IXTQ for intermittent exotropia need
to account for spectacle wear.
CR: T. Yamada, None; S.R. Hatt, None; D.A. Leske, None; J.M. Holmes, None.
Support: NIH Grant EY015799 (JMH), Research to Prevent Blindness, Inc., and Mayo
Foundation
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1983-1986
Monday, May 4, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 1979 - 1998 / D754 - D773
264. Strabismus II Organizing Section: EY
1987 - D762
Defining Real Change of Health Related Quality of Life Scores in Adults With
Strabismus
D.A. Leske, S.R. Hatt, J.M. Holmes. Department of Ophthalmology, Mayo Clinic,
Rochester, MN.
Purpose: Treatment for strabismus aims to improve function and health related
quality of life (HRQOL), but real change in HRQOL scores has not been rigorously
defined using test-retest data. The purpose of this study is to define real change in
HRQOL scores in a cohort of strabismus patients using strabismus-specific and general
vision-related HRQOL instruments.
Methods: 12 adult patients with stable strabismus and no intervening treatment
completed the NEI VFQ-25 and the new Adult Strabismus 20 (AS-20) HRQOL
instruments. Questionnaires were completed a second time at a subsequent office visit.
Test-retest differences were compared and 95% limits of agreement (LOA), a threshold
value for real change, were calculated for composite scores and subscale scores.
Results: As expected for a test-retest study, no statistically significant changes were
seen in composite HRQOL scores or subscale scores for either the AS-20 or VFQ-25
(P = 0.08 to 1.0, signed rank). For the AS-20, the 95% LOA for the composite score was
17.3 points. The 95% LOA was 25.9 for the AS-20 functional subscale and 19.2 for the
AS-20 psychosocial subscale. For the VFQ-25 composite score, the 95% LOA was 14.0.
95% LOAs for the VFQ-25 subscales ranged from 0 (no variability due to a ceiling
effect) to 56.6 (large variability). Previous studies have identified peripheral vision and
vision-specific social functioning, mental health, role difficulties, and dependency
subscales as useful for diplopic patients but not non-diplopic patients. These subscales
had 95% LOAs of 45.9, 21.2, 28.7, 24.7 and 12.1 respectively.
Conclusions: A change of 17 points or more on the AS-20 is indicative of a real change
of HRQOL in patients with strabismus. The VFQ-25 may be less useful for quantifying
strabismus-specific HRQOL issues due to ceiling effects, large variability, and large
LOA’s on several subscales. These data can now be used for responsiveness studies to
further evaluate the usefulness of these instruments in assessing HRQOL of adults
with strabismus.
CR: D.A. Leske, None; S.R. Hatt, None; J.M. Holmes, None.
Support: NIH Grant EY015799 (JMH), Research to Prevent Blindness, Inc., and Mayo
Foundation
1989 - D764
Slow-Releasing All-Trans-Retinoic Acid in Polytetrafluoroethylene/PolylactideCo-Glycolide Laminate Delays Adjustment After Strabismus Surgery in Rabbit
Model
C. Kee1, J.-M. Hwang2, M. Lee3, T.-W. Kim 3, H.-K. Choungv3. 1Ophthalmology,
Samsung Medical Center, SKK Univ., Seoul, Republic of Korea; 2Ophthalmology,
Seoul National University College of Medicine, Seongnam, Republic of Korea;
3
Ophthalmology, Seoul National University College of Medicine, Seoul, Republic
of Korea.
Purpose: To determine the usefulness of slow-releasing all-trans-retinoic acid (ATRA)
in polytetrafluoroethylene/polylactide-co-glycolide (PTFE/PLGA) laminate for delayed
adjustable strabismus surgery.
Methods: A prospective, masked-observer, controlled study was performed in 25
rabbits. Fifty rabbit eyes were divided randomly into three groups. After a recession
of the superior rectus muscle (SRM), a PTFE/PLGA laminate containing ATRA, PTFE
alone, or balanced salt solution was applied beneath and over the SRM in the PTFE/
PLGA-ATRA group (group ATRA), the PTFE group (group PTFE) and the control
group, respectively.
Results: At 5 weeks postoperatively, group PTFE and group ATRA showed better
adjustability than the control group. In addition, there was less adhesion in group
PTFE or group ATRA than the control group in terms of adhesion between SRMs and
conjunctivae at 5 weeks postoperatively. Only group ATRA showed less adhesion
than the control group in terms of adhesion between SRMs and sclerae at 5 weeks
postoperatively.
Conclusions: Slow-releasing ATRA in PTFE/PLGA was found to reduce adhesion and
allowed delayed adjustment in most eyes for up to five weeks postoperatively.
CR: C. Kee, None; J.-M. Hwang, None; M. Lee, None; T.-W. Kim, None; H.-K.
Choungv, None.
Support: a grant of the Korea Health 21 R&D Project, Ministry of health, welfare and
family affairs, Republic of Korea (A080299)
1988 - D763
Saccade Abnormality in Idiopathic Intracranial Hypertension
Y.-R. Chen, Y.J. Liao. Ophthalmology, Stanford University, Stanford, CA.
Purpose: To characterize the horizontal saccade abnormality and to assess the
effectiveness of acetazolamide in patients with idiopathic intracranial hypertension
(IIH).
Methods: We recruited 13 consecutive patients with IIH regardless of symptoms of
presentation for clinical assessment and eye movement recording at an academic
institution over one year. Six patients had paired recordings that allowed intra-subject
comparison of the efficacy of acetazolamide treatment. Binocular infrared oculography
at 500 Hz was performed before and during acetazolamide treatment. Randomized,
repetitive visual stimuli were presented with custom program written in Presentation.
Data was analyzed with custom-written programs in MATLAB and IgorPro.
Results: While most patients had no symptomatic binocular diplopia at presentation,
those with clinically evident abduction abnormality exhibited small esophoria in
primary gaze, which worsened at left or right gaze. Reflexive horizontal saccades
showed bilateral or unilateral abduction deficits in the majority of patients with IIH.
This was evident during the plateau phase of the saccade as well as in the initial
dynamic overshoot. In 6 patients with paired recording, 83% had abduction deficits.
The difference between the abducting and adducting eyes in 12 degree rightward
saccades was 0.984 ± 0.202 deg, and for 12 degree leftward saccades, 0.809 ± 0.159 deg.
Treatment with acetazolamide (1000-2000 mg per day) led to the rapid resolution
of abduction deficit and ocular misalignment, with the average plateau difference
of rightward saccade improving by 86% (0.134 ± 0.153 deg, n = 6, P = 0.0016), and
the leftward saccade improving by 67% (0.267 ± 0.154 deg, n = 6, P = 0.0175). The
amelioration of ocular mismatch during reflexive saccades occurred early, well before
the resolution of papilledema.
Conclusions: Abduction deficit, most likely a result of cranial nerve VI dysfunction
due to elevated intracranial pressure, occurred in more than 50% of patients with IIH,
even in the absence of subjective binocular diplopia. This abnormality quickly resolved
following acetazolamide treatment. Our study highlighted the utility of eye movement
recording in assisting the diagnosis and monitoring of patients with IIH.
CR: Y.-R. Chen, None; Y.J. Liao, None.
Support: Career Award in Biomedical Sciences from the Burroughs Wellcome
Foundation, NIH Grant K08 NS044268, Stanford Medical Scholars Program.
1990 - D765
Vertical Vergence Adaptation Produces an Incomitant Transient Cyclovertical
Deviation Changing With Gaze Direction and Head Tilt
H.S. Ying1A, K. Irsch1B, N.A. Ramey1B, D.L. Guyton1B. ARetina, BPediatric
Ophthalmology and Strabismus, 1Johns Hopkins Wilmer Eye Institute, Baltimore,
MD.
Purpose: With the aim of understanding the cyclovertical mechanisms involved in
both binocular fusion and ocular misalignment, we asked normal volunteers to adapt
to a steadily increasing vertical misalignment.
Methods: We designed and built a novel research haploscope capable of tilting with the
subject 45 degrees to the right or the left about the naso-occipital axis and measuring
binocular horizontal, vertical, and torsional eye movements with video oculography.
Circular targets consisting of multicolored concentric circles without torsional cues
and subtending >54 degrees were used to stimulate vertical vergence. Two subjects
with normal orthoptic exams were instructed to fuse a gradually increasing right
over left target disparity in straight head position for 30 minutes. Static eye positions
were measured during monocular viewing in the nine diagnostic positions of gaze
(10-degree excursions) with head straight and tilted 45 degrees right and left. Subjects
re-fused right over left target disparity between measurements in different head
tilts.
Results: After adaptation, both subjects developed a transient cyclovertical ocular
deviation with at least two degrees of vertical deviation in the straight ahead position.
The right hyperdeviation decayed slowly over 60 to 90 seconds. This hyperdeviation
increased in down gaze or with 45-degree left tilt and reduced with 45-degree right
head tilt. Relative extorsion that was greatest in left gaze developed in all three head
tilts. An esodeviation also developed in most positions of gaze which increased with
tilt to either side.
Conclusions: Changes in a vertical deviation with head tilt are often taken as evidence
for a cyclovertical muscle paresis. These results indicate that vergence adaptation may
induce a transient cyclovertical deviation that can also show changes with head tilting.
Therefore, changes in vertical deviation with head tilting are not pathognomonic of
cyclovertical muscle paresis.
CR: H.S. Ying, None; K. Irsch, None; N.A. Ramey, None; D.L. Guyton, None.
Support: NIH Grant EY19347, NIH Grant EY15025, Knights’ Templar Eye Foundation
Young Investigator Award, Research to Prevent Blindness
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1987-1990
Monday, May 4, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 1979 - 1998 / D754 - D773
264. Strabismus II Organizing Section: EY
1991 - D766
Influence of Physiologic Diplopia Suppression on Phoria Maintenance in
Inttermittent Exotropia
1992 - D767
Surgical Correction of Childhood Intermittent Exotropia Does Not Influence
the Development of Mental Illness
A. Wakayama, K. Ohmure, F. Matsumoto, K. Abe, Y. Shimomura. Ophthalmology, Kinki
Univ Sch of Medicine, Osaka-Sayama, Japan.
R.A. Barraza1A, J.A. McKenzie1B, N.N. Diehl2, B.G. Mohney3. AMayo Medical Scientist
Training Program, BCollege of Medicine, 1Mayo Clinic College of Medicine,
Rochester, MN; 2Division of Biostatistics, Mayo Clinic College of Medicine and
Mayo Foundation, Jacksonville, FL; 3Department of Ophthalmology, Mayo Clinic
College of Medicine and Mayo Foundation, Rochester, MN.
Purpose: Because control of phoria is important for managing intermittent exotropia,
we investigated how the maintenance of phoria could be affected by suppression of
physiological diploia.
Methods: Subjects were 50 patients with intermittent exotropia, who were under
15 years old (mean age, 9.0±2.3 years) and could be examined for suppression of
physiologic diplopia. Thirty-four of the 50 patients had received one operation,
orthoptic training, or both previously; and 23 of the 34 patients could maintain
phoria after treatment. Deviations at near and far distances were 20.3±9.3PD and
18.0±8.7PD, respectively. Presence of suppression was assessed under phoria condition
by physiologic diplopia test and when convergence broke. Relationships between
phoria maintenance and suppression, non-dominant eye and deviating eye when
convergence broke, and dominant eye and dominant hand were all investigated.
Results: Twenty-two (44.0%) of the 50 patients showed suppression of physiological
diplopia under phoria condition, and 18 (81.1%) of the 22 patients also indicated
suppression when convergence broke. A significant correlation was seen between
suppression under phoria condition and when convergence broke (p<0.001). Twentythree (46%) of the 50 patients indicated phoria maintenance and only 2 (8.7%) of them
showed suppression under both conditions. This indicated that patients capable of
phoria maintenance did not suppress under phoria condition and when convergence
broke. In those 27 patients not capable of phoria maintenance, 16 (59.3%) were seen
with suppression under both conditions. This suggested that patients not capable
of phoria maintenance suppressed under phoria condition and when convergence
broke. A significant correlation was seen between the presence of suppression and
the maintenance of phoria (p<0.001). Deviating eye when convergence broke and nondominant eye corresponded in 87.1% of the 50 patients. Dominant eye and dominant
hand corresponded in 68.0%.
Conclusions: Under phoria condition, patients who can maintain phoria condition
did not suppress. This shows the association between the presence of suppression
and maintenance of phoria.
CR: A. Wakayama, None; K. Ohmure, None; F. Matsumoto, None; K. Abe, None; Y.
Shimomura, None.
Support: None
Purpose: We recently demonstrated that children with intermittent exotropia,
compared to age- and gender-matched controls, are at an increased risk for developing
mental illness by early adulthood. The purpose of this study was to assess whether
surgical intervention, or the timing of intervention, had any effect on the prevalence
of mental illness.
Methods: The medical records of all children (<19 years) diagnosed with intermittent
exotropia (n = 183) as residents of Olmsted Country, Minnesota, between January 1,
1975, and December 31, 1994, were retrospectively reviewed for parameters concerning
treatment and the development of mental illness.
Results: Ninety-seven (53.3%) of the 183 children were diagnosed with a mental
illness when followed to a mean age of 23.3 years (range, 6 to 41 years). Thirty three
(34%) of the 97 children who developed mental illness underwent surgery while the
remaining 64 did not have surgery (p=0.75). Neither age at surgery (< 10 years of age)
(p=0.98) nor success at surgery (< 10 prism diopters) (p=0.66) were associated with
a decreased occurrence of mental illness by early adulthood. Additionally, of the 86
patients who did not develop mental illness, strabismus surgery, when it occurred,
was not more common (p=0.71) or at a younger age (p=0.15) when compared to the
97 patients who later developed mental illness.
Conclusions: Strabismus surgery, regardless of success or age at surgery, for children
with intermittent exotropia did not decrease or otherwise alter the development of
mental illness by early adulthood.
CR: R.A. Barraza, None; J.A. McKenzie, None; N.N. Diehl, None; B.G. Mohney,
None.
Support: Research to Prevent Blindness
1993 - D768
Detection of Socially Significant Strabismus by Lay Observers in a Culturally
Diverse Model Set
1994 - D769
Does Strabismus Surgery Improve Functional Outcomes in Children With
Cerebral Palsy? Gross Motor Function Classification Scale
K.W. Chan1,2A, E.M. Weissberg2A, L. Deng2B. 1Pediatric Ophthalmology and
Strabismus, Massachusetts Eye and Ear Infirmary, Boston, MA; ASpecialty and
Advanced Care, BVision Science, 2New England College of Optometry, Boston, MA.
F.F. Ghasia1A, J. Brunstrom1B, L. Tychsen1C. ADept of Ophthal and Visual Sciences,
B
Dept of Neurology, Dept of Pediatrics, CDept of Ophthal and Visual Sciences, Dept
of Pediatrics, 1Washington University St Louis, St. Louis, MO.
Purpose: Patients with socially significant strabismus may suffer both visual and
psychosocial consequences. The magnitude at which strabismus becomes socially
significant is unclear. Previous publications have suggested exotropia (XT) is easier
to detect than esotropia (ET), with critical magnitude of detection (>70% detection)
described at approximately 8Δ for XT and 14.5Δ for ET. However, both these studies
used only one, female, Caucasian model. This study will further examine the critical
magnitude of detectable strabismus by lay observers in a more culturally diverse
model set.
Methods: Twelve models of variable ethnicity (4 African American (AA), 4 Asian (AS)
and 4 Caucasian (CA)) with equal number of female and male models within each
race were digitally photographed in a range of horizontal gaze positions. Strabismus
ranging from ET 21Δ to XT 21Δ was simulated using photo manipulation. Images
were presented in a randomized order to 102 non-health care professional observers
who were asked to decide whether strabismus was present or not. The magnitude of
strabismus with a 70% positive response rate was defined as the critical magnitude.
Results: Overall, an increase in likelihood of strabismus detection was noted as
the angle of strabismus increased. For all models combined, critical magnitude for
detecting ET was 18.82Δ (95% C.I. (18.34Δ, 20.38Δ)) and XT was 16.63Δ (95% C.I. (15.46Δ,
17.26Δ)), indicating XT was slightly easier to detect than ET. Differences were noted
among race. The critical magnitude for detecting ET for AS models was 14.25Δ (12.91,
15.60) compared to 20.88Δ (18.54, 25.32) for XT. AA and CA data showed an opposite
trend with critical magnitude being 20.82Δ (19.26, 22.37) for ET and 16.29Δ (15.52, 17.25)
for XT in AA models and 23.17Δ (20.43, 27.43) for ET and 13.53Δ (12.70, 14.64) for XT in
CA models. The positive response rate at ortho position (false positive rate) was lowest
for AA followed by CA with a higher response rate for AS models. Large variability in
critical magnitude of detection was found among the 12 models implying no uniform
detection angle may exist across individuals.
Conclusions: XT was slightly easier to detect than ET for all models combined. Race
differences were observed with ET being easier to detect than XT in AS models and
the opposite trend in AA and CA models. Large inter-model variability may suggest
difficulty generalizing results of this and similar studies and raises the question
whether guidelines for socially significant strabismus can be applied to an entire
population.
CR: K.W. Chan, None; E.M. Weissberg, None; L. Deng, None.
Support: NEI Grant R24 EY014817
Purpose: To determine binocular sensory and motor outcomes after strabismus
surgery in children with cerebral palsy (CP).
Methods: A cross-sectional observational study was conducted on 50 children whose
CP severity spanned milder (level 1-2) to severe (level 3-5) using the standardized
Gross Motor Function Classification System. Optimal motor outcome was defined as 8
PD or less deviation (microtropia) 1 yr post-surgery; sensory outcome was defined as
restoration of fusion or stereopsis. Mean age = 3.5 yrs; mean follow-up = 4.1 yrs. Across
GMFCS levels children did not differ in gestational age, examination age, preoperative
angle or follow-up period (ANOVA p=0.9, p=0.23, p=0.53 respectively).
Results: Children with mild CP achieved a 2.6x greater rate of optimal motor outcome
and 3.1x greater stereopsis outcome compared to children with severe CP (50% vs.
19% and 25% vs. 8%). Gain of binocularity was 1.7x greater in children with primary
ET (63%) versus primary XT (37%). Outcomes did not differ in children with stable
vs. variable-angle preoperative deviation (chi sqr p=0.5). In primary ET children,
38% had optimal motor outcome after 1 surgery and 71% after 2 surgeries. 42%
of primary ET children developed a secondary macro XT after 1 surgery, which
responded favorably to a 2nd surgery. Shorter duration of strabismus before surgery 1
was associated with better motor outcome [2.6 yrs vs. 4.3 yrs in suboptimal-macrotropia
outcome (p=0.05)] and gain in binocularity [2.1 yrs vs. 4.8 yrs (p=0.05)]. Children with
dyskinetic strabismus (variable ET/XT) did not achieve optimal motor outcome or
gain in binocularity.
Conclusions: Children with milder CP, primary ET and earlier treatment benefit
substantially from strabismus surgery. Variable deviation and secondary XT is
common, but should not deter earlier treatment.
CR: F.F. Ghasia, None; J. Brunstrom, None; L. Tychsen, None.
Support: 5-T32-EY13360-05 ,1 F32 EY016964-01A1 ,Gustavus and Louise Pfeiffer
foundation,Walt and Lilly Disney Scholars Award for Amblyopia Research
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1991-1994
Monday, May 4, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 1979 - 1998 / D754 - D773
264. Strabismus II Organizing Section: EY
1995 - D770
Long Term Outcomes, in Different Degrees of Compliance With Wearing
Spectacles, in Children With Accommodative Esotropia
1996 - D771
Appearance of V Pattern Strabismus and Inferior Oblique Overaction After
Sixth Nerve Palsy in Children
M.A. Hussein, D.R. Weakley. Ophthalmology, UTsouthwestern medical center,
Dallas, TX.
S.M. Culican, S. Khanna. Ophthal & Vis Sciences, Washington University, Saint
Louis, MO.
Purpose: The aim of this study is to evaluate, retrospectively, the long term outcome
of children with accommodative esotropia, who are not compliant with wearing
their spectacles.
Methods: We reviewed the charts of patients who had a diagnosis of accommodative
esotropia , had at least 3 diopters of hyperopia , and who had at least one year of
follow up. We divided patients according to the degree of compliance with wearing
spectacles into good , fair , and poor compliance.The main outcome measures for
treatment were the sensory and motor outcomes.
Results: Ninety two patients met our inclusion criteria. The mean follow up was 61.4
months (from 12 to 200 months).When comparing patients with good compliance to
those with fair compliance, fair compliance was associated with significant higher risk
for poor sensory outcome (Odd Ratio 4.5507, 95% CI from 2.1 to 24.7, P value = 0.0003 ),
and poor motor outcome (Odd Ratio, 4.11, 95% CI from 1.44 to 11.75, P value = 0.0065).
When comparing patients with good compliance to those with poor compliance, poor
compliance was associated with higher risk for poor sensory outcome (Odd Ratio,
12.3236, 95% CI from 1.29 to 96.79, P value = 0.0061) and motor outcome(Odd Ratio,
11.6644, 95% CI from 2.38 to 74.19, P value = 0.0006 )
Conclusions: Our results underscore the importance of finding alternative ways for
managing non-compliant children with accommodative esotropia.
CR: M.A. Hussein, None; D.R. Weakley, None.
Support: None
Purpose: To study the occurrence of primary inferior oblique overaction and V pattern
strabismus with acquired sixth nerve palsy in children.
Methods: Retrospective chart review of ophthalmologic/ orthoptic examination of
patients with isolated sixth nerve palsy seen in the children’s Eye Clinic over the last
5 years. 5 patients met the criteria for isolated sixth nerve palsy.
Results: Two of the five patients had bilateral sixth nerve palsies that resolved
completely with no residual esotropia (ET). These patients did not manifest any
inferior oblique overaction (IOOA) at any time. Three patients manifested residual
ET at the 2-3 months follow-up visit and manifested inferior oblique overaction. Two
of these three patients had unilateral palsy with onset of IOOA on the ipsilateral
side of the sixth nerve palsy. One patient with bilateral sixth nerve palsy developed
IOOA bilaterally.
Conclusions: Children who suffer sixth nerve palsy and have residual esotropia
develop the ocular motor signs of primary inferior oblique overaction. We speculate
that in these children there is residual orbital layer weakness of the lateral rectus
which displaces the lateral rectus pulley, thereby altering the dynamics of inferior
oblique action and manifesting as IOOA.
CR: S.M. Culican, None; S. Khanna, None.
Support: NEI- K12 EY016336
1997 - D772
Effectiveness of Placebo Therapy for Maintaining Masking in a Clinical Trial of
Vergence/Accommodative Therapy
1998 - D773
Improvement in Academic Behavior Following Successful Treatment of
Convergence Insufficiency
M.T. Kulp1, G.L. Mitchell1, E. Borsting2, M. Scheiman 3, S. Cotter2, M. Rouse2, S. Tamkins 4,
B.G. Mohney5, A. Toole1, CITT Study Group. 1College of Optometry, Ohio State
University, Columbus, OH; 2College of Optometry, Southern California, Fullerton,
CA; 3Pennsylvania College of Optometry, Salus University, Philadelphia, PA;
4
Bascom Palmer Eye Institute, Miami, FL; 5Mayo Clinic, Rochester, MN.
E. Borsting1, M.W. Rouse1, L. Mitchell2, M.T. Kulp2, M. Scheiman 3, S. Cotter1, CITT
Study Group. 1Clinical Science, Southern California Coll of Optometry, Fullerton,
CA; 2College of Optometry, Ohio State University, Columbus, OH; 3Pennsylvania
College of Optometry, Salus University, Philadelphia, PA.
Purpose: To determine if demographic variables affected masking of subjects in the
Convergence Insufficiency Treatment Trial (CITT) and whether perception of assigned
treatment group was associated with treatment outcome or adherence to treatment. We
also evaluated the effectiveness of the CITT placebo therapy program in maintaining
masking of patients randomized to the office-based treatment arms.
Methods: Patients (n=221, ages 9 to 17 years) were randomized to one of 4 treatment
groups; 2 of which were office-based and masked to treatment (n=114). The placebo
therapy program was designed to appear like real vergence/accommodative therapy,
without stimulating vergence, accommodation, or fine saccades (beyond levels of
daily visual activities). After treatment, patients in the office-based groups were
asked if they thought they received real or placebo therapy and how confident they
were in their answer.
Results: Ninety-three percent of patients assigned to real therapy and 85% assigned
to placebo therapy thought they were in the real therapy group (p=0.17). No
significant differences were found between the two groups in adherence (p≥0.22 for
all comparisons). The percentage of patients who thought they were assigned to real
therapy did not differ by age, gender, race or ethnicity (p > 0.30 for all comparisons).
No association was found between patients’ perception of group assignment and
symptoms or signs at outcome (p≥0.38 for all comparisons).
Conclusions: The CITT placebo therapy program was effective in maintaining patient
masking in this study and, therefore, may potentially be used in future clinical trials
using vergence/accommodative therapy. Masking was not affected by demographic
variables. Perception of group assignment was not related to symptoms or signs at
outcome.
CR: M.T. Kulp, None; G.L. Mitchell, None; E. Borsting, None; M. Scheiman, None; S.
Cotter, None; M. Rouse, None; S. Tamkins, None; B.G. Mohney, None; A. Toole,
None.
Support: U10EY014713, U10EY014659, U10EY014716, U10EY014715, U10EY014709,
U10EY014710, U10EY014676, U10EY014706, and U10EY014712 from the National Eye
Institute CT: www.clinicaltrials.gov, NCT00338611
Purpose: To determine whether successful treatment of Convergence Insufficiency
(CI) has an impact on parents’ perceptions of the frequency of problem behaviors that
their child may exhibit when reading or performing school work (such as: difficulty
completing work, avoidance, and inattention) and parental concern about academic
performance as measured by the Academic Behavior Survey (ABS).
Methods: The ABS was administered at baseline and after 12 weeks of treatment to the
parents of 218 children ages 9-17 years with symptomatic CI, who were enrolled in the
Convergence Insufficiency Treatment Trial and randomized into one of four treatment
groups. The ABS is a 6-item survey that quantifies the frequency of observed behaviors
and parental concern on an ordinal scale from 0 (never) to 4 (always) with a total score
ranging from 0 to 24. Participants were classified as successful (n=42), improved (n=60),
or non-responder (n=116) at the completion of 12 weeks of treatment using a composite
measure of the CI Symptom Survey, near point of convergence, and positive fusional
vergence. Analysis of covariance methods were used to compare the mean change in
ABS between the groups while controlling for the ABS score at baseline.
Results: The mean ABS score for the entire group at baseline was 12.85 (SD=6.3). The
mean ABS score decreased in those categorized as successful, improved, and nonresponder by 4.0, 2.9, and 1.3 points respectively. The improvement in the ABS score
was significantly related to treatment outcome (p<0.0001).
Conclusions: Improvements in the signs and symptoms of CI after treatment were
associated with a reduction in the frequency of problem behaviors associated with
reading and school work as reported by parents on the ABS.
CR: E. Borsting, None; M.W. Rouse, None; L. Mitchell, None; M.T. Kulp, None; M.
Scheiman, None; S. Cotter, None.
Support: Supported by NEI/NIH, DHHS U10 grants: EY014713, EY014659, EY014716,
EY014715, EY014709, EY014710, EY014676, EY014706, EY014712 CT: www.clinicaltrials.
gov, NCT00347945
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
1995-1998
Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2827 - 2840 / A82 - A95
323. Nystagmus Organizing Section: EY
2827 - A82
Normative Data on Maximum Angle of Abduction and Nystagmus Onset Angle
R.M. Williams1, S.B. Stevenson1, J.M. Wensveen1, S.J. Rubenzer2. 1College of Optometry,
University of Houston, Houston, TX; 2Private Practice, Houston, TX.
Purpose: Horizontal Gaze Nystagmus is assessed by law enforcement as one part of
the Standardized Field Sobriety Test, where nystagmus that occurs at gaze angles less
than 45 degrees increases suspicion of intoxication, though little normative data have
been reported on gaze evoked nystagmus, or on the role of factors such as fatigue. We
measured the maximum angle of abduction and the angle of onset of nystagmus in
103 sober individuals, and looked for fatigue effects in 4 subjects.
Methods: Subjects were seated with head stabilized and positioned so that the left
eye was directly over the pivot of a rotating arm carrying a camera, infrared LED
source, and a small mirror. The camera provided experimenters with a magnified
view of the eye that stayed on axis with gaze direction as the arm rotated. The arm
was moved in 5 degree increments, and gaze stability and accuracy were assessed at
each position. Nystagmus onset was recorded as the smallest angle at which distinct
nystagmus of at least 3 beats was noted. Maximum deviation was recorded as the
largest angle for which the target remained centered in the pupil image. For the
large sample, measurements were made on optometry students during a morning
laboratory exercise. For the fatigue study, repeated measures were made on both eyes
of 4 subjects at 3 different times of day spanning a 12 hour period. Measurements
were repeated on 5 days.
Results: The maximum angle of abduction varied from 35 to 65 degrees, with mean
of 48 +/- 5.9 degrees. Nystagmus occurred in 70/103 subjects, with a mean angle of
onset 44 +/- 6.0 degrees. For 28/103 subjects the angle of onset was the same as the
maximum deviation. The fatigue study showed that both measures increased slightly
with time of day but the effect was not significant (repeated measures ANOVA, df
3, 2, F 1.952, p 0.2449).
Conclusions: End gaze nystagmus is a common finding in the general population,
suggesting that the roadside HGN test may suffer from a high false positive rate. 70
of 103 subjects showed nystagmus at max deviation, and half of our sample showed
nystagmus at or before 45 degrees. Fatigue did not have a significant effect on the
occurrence or magnitude of nystagmus in our sample.
CR: R.M. Williams, None; S.B. Stevenson, None; J.M. Wensveen, None; S.J.
Rubenzer, None.
Support: NIH grant T35 EY07088-18
2828 - A83
Increasing Salience of the Moving Stimulus Impairs OKN Suppression More
Than Does Spreading Spatial Attention
L.A. Abel1, H.N. Nguyen1, C.J. Lueck 2, I.M. Williams3. 1Optometry & Vision Sciences,
University of Melbourne, Carlton, Australia; 2Neurology, Canberra Hospital,
Canberra, Australia; 3Medicine, Monash University, Melbourne, Australia.
Purpose: Although a full-field high contrast stimulus rotating around a subject
elicits a strong response of optokinetic nystagmus (OKN), normal individuals can
suppress this nearly completely by actively fixating a stationary point in the otherwise
moving environment. This requirement for active fixation raised the possibility
that if attention were simultaneously directed elsewhere in the visual field, then
OKN suppression might be impaired. In a recent study (Williams et al, 2006) we
demonstrated that if subjects were required to detect the first appearance of a feature
of the OKN stimulus (a red T in a row of red Cs and blue Ts), that OKN suppression
declined in an age-dependent manner. It was unclear, however, whether this was
due to directing attention towards the OKN stimulus or to having to spread it over a
wide spatial area. The present study addresses this question.
Methods: 15 healthy subjects aged sat in the centre of a full-field stimulus 1.5 m in
diameter moving at 24°/s and composed of columns of red Cs and blue Ts, with the
eye-level row also containing 3 red Ts. Red laser spots were projected on the curtain
under computer control at 0° and 7.5° left or right. After baseline “stare” OKN testing,
all other tasks required subjects to fixate a 0° spot. 3 tasks required detection of a
blink of either the central or peripheral laser spot and 3 required detection of a red
T passing the same spots. OKN gain was measured for all tasks and compared with
Friedman’s ANOVA and also regressed against subjects’ ages.
Results : Mean gains on the 3 blink detection tasks were 0.06, 0.05 and 0.06; on the
corresponding T detection tasks they were 0.14, 0.15 and 0.16. ANOVA showed a
significant main effect of task on gain (p<.001); pairwise post-hoc tests found significant
gain differences (p<.05) when detecting blinks vs. detecting red Ts. Regressions against
age were all non-significant.
Conclusions: For the 6 detection tasks, stimulus conditions were identical across the
pairs of tasks but attention was directed either towards the moving curtain or the static
laser spot at each location. Gain was significantly higher when the OKN stimulus was
made more salient via top-down allocation of attention. The lack of an age effect may
result from 7.5° targets not sufficiently stretching the attentional spotlight to stress
even elderly subjects’ resources.
CR: L.A. Abel, None; H.N. Nguyen, None; C.J. Lueck, None; I.M. Williams,
None.
Support: None
2829 - A84
The Clinical Spectrum of Involuntary Horizontal “End-on-End” Saccades
2830 - A85
Hyper Acuity Target Improve Fixation Stability
M.L. Rosenberg. Neurology, New Jersey Neuroscience Institute, Edison, NJ.
T. Pansell1, S. Giovagnoli2, R. Bolzani2, B. Zhang1, J. Ygge1. 1Ophthalmology
Department, Karolinska Institutet, Stockholm, Sweden; 2Psychology Department,
Bologna University, Bologna, Italy.
Purpose: Voluntary nystagmus is a well known entity most commonly encountered in
the setting of a patient seeking secondary gain. At times however voluntary nystagmus
can be indistinguishable from ocular flutter either by clinical exam or by eye movement
recordings. The situation can be made more complex as there are patients reported
who admit to spells of voluntary nystagmus but also note episodes that are said not
to be under their control. To try and better understand this condition patients with
end on end saccades from any condition were collected retrospectively from cases
seen by the author.
Methods: Patient records available for computer searching were evaluated for cases
noted on clinical examination to have end on end saccades. Other clinical findings,
the final diagnosis and radiological findings were gathered from the clinical and
the hospital records. Patients who admitted to voluntary nystagmus or who had
evidence of secondary gain or other psychological difficulties were excluded. Patients
with micro-flutter were also not included in this study. 66 patients were included
in this study.
Results: Of the 66 patients 13 were found to have involuntary flutter-like movements
on exam but were diagnosed as being normal. 48 were found to have a specific
neurological disagnosis while 5 had neurological problems of unclear etiology. The
most common diagnosis was multiple sclerosis. The abnormal saccades were noted
at times to be induced by convergence (26), saccades (6), or pursuit movements (6),
while at other times were spontaneous (46).
Conclusions: Not all patients with what appears to be ocular flutter have an underlying
neurological problem, although most do. Similarly not all those with what appears
to be voluntary nystagmus are free of underlying neurological disease. All patients
with spontaneous flutter or flutter induced by pursuits or saccades, who did not have
similar movements inducible by convergence, had neurological disease. All subjects
with flutter-like movements induced by saccades were also found to have underlying
neurological disease. Ocular flutter, with or without an association with convergence,
was rarely the only sign on initial exam of neurological disease. Although clinically
difficult at times, it is critically important to distinguish voluntary nystagmus from
ocular flutter. Although psychological disorders are not always clinically obvious, the
absence of a clear secondary gain should be an important clue to look for a possible
organic process.
CR: M.L. Rosenberg, None.
Support: None
Purpose: A slow oscillation of eye position (±0.5 deg, 0.1 Hz) was recently described
when analyzing fixational eye movements by means of a Fourier transformation
(poster Zhang et al., ARVO 2009). The underlying purpose of this eye movement is not
known. This study investigated the influence of hyper acuity targets on this ocular
oscillation. Many studies have reported that the visual hyperacuity, the ability to
perceive visual information presented under the threshold of visual acuity is mainly
related to the magnocellular system, which is supposed to be of advantage for visual
stabilization. Our hypothesis is that the fixation of a hyper-acuity target is more stable
than the fixation of a super threshold target.
Methods: Eye movements were recorded binocularly (VOG, Chronos Vision; 100
Hz) in seven healthy subjects during a fixation task. Three targets were used in a
randomized procedure for each subject in three tests (180 sec). i) hyper-acuity target
(dot obtained by a number of concentric circles with distances between each other
under the visual acuity threshold) ii) visible target (dot made by concentric circles
with distances each other over the visual acuity threshold), and iii) solid target
(control target, a grey dot). All the targets had the same luminosity (23 cd/m²), size
(visual angle 0.9 deg) and were presented at the same eye-screen distance (50 cm).
The subjects were instructed to fixate the target.
Results: Significant differences were found in the characteristics of the oscillation
between the targets (F=2.49; p< .05). The oscillation was faster and the amplitude was
smaller in response to the hyper acuity target compared to the other two targets. The
faster oscillation might be caused by a constant eye velocity in a narrower fixation
area.
Conclusions: These results suggest that the oscillation of fixational eye movements
is more stable when fixating a hyper acuity target. Fixation is more stable when only
the magnocellular system is stimulated compared to when both the parvocellular
and mangocellular systems are involved.
CR: T. Pansell, None; S. Giovagnoli, None; R. Bolzani, None; B. Zhang, None; J.
Ygge, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
2827-2830
Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2827 - 2840 / A82 - A95
323. Nystagmus Organizing Section: EY
2831 - A86
Torsional Optokinetic Nystagmus in Strabismus
2832 - A87
Survey of Diagnosis of Nystagmus in the United Kingdom
S.J. Farooq, R.J. Mclean, F.A. Proudlock, I. Gottlob. Ophthalmology, University of
Leicester, Leicester, United Kingdom.
I. Choudhuri1, N. Sarvananthan1, I. Gottlob2. 1Ophthalmology, Leicester Royal
Infirmary, Leicester, United Kingdom; 2Ophthalmology, University of Leicester,
Leicester, United Kingdom.
Purpose: Torsional optokinetic Nystagmus (tOKN) in patients with strabismus since
childhood has not been previously evaluated. The authors investigated the optokinetic
response in horizontal, vertical and torsional directions in strabismus patients and
in age-matched normal volunteers.
Methods: Monocular torsional, horizontal and vertical eye movements were recorded
in 16 subjects with childhood strabismus and 15 normal volunteers. Constant velocity
horizontal (nasalward and temporalward) and vertical (upward and downward) OKN
stimuli were used at 10°/s, 20°/s and 40°/s. Torsional (intorsion and extorsion) OKN
stimuli were rotated at velocities of 40° and 400°/s.
Results: OKN responses from strabismus patients produced significant asymmetric
responses in horizontal and vertical meridians. The nasalward response was
significantly greater than the temporalward (p=3.64x10 -6 for the non-dominant eyes,
p=7.18x10 -9 for the dominant eyes) and upward response was greater than downward
(p=0.0029 for the non-dominant eyes, p= 0.0043 for the dominant eyes. A significant
high incidence of absent tOKN was present at both stimulus velocities in the intorsion
direction (p= 0.024 for 40°/s, p=0.0085 for 400°/s) and at 400°/s in the extorsion direction
(p= 0.040). Eight of the 15 patients tested did not respond to any stimulus in either
direction in their non-dominant eye and 4 showed no response in their dominant
eye.
Conclusions: Torsional OKN is dramatically affected in the presence of strabismus
with a high incidence of no response. The possibility of a lack of development in the
binocular cortical structures that respond to torsional motion could explain these
findings.
CR: S.J. Farooq, None; R.J. Mclean, None; F.A. Proudlock, None; I. Gottlob,
None.
Support: None
Purpose: Nystagmus causes significant symptoms of visual reduction with or without
oscillopsia in many individuals. There is no consensus regarding the best way to
investigate these patients.
Methods: A questionnaire was sent to all ophthalmologists in the United Kingdom.
Information about sub-speciality interest, examinations/investigations done for
nystagmus patients, and investigations they would like to be available for nystagmus
patients were collected.
Results: Out of 893 questionnaires sent, 411were returned
Twenty one responses were from neuro-ophthamologists, 108 were from paediatricophthalmologists, 12 declared overlapping neuro/paediatric interests, while the
remaining were from other ophthalmic specialities. The examinations currently done by
ophthalmologists as routine were, orthoptic examinations (n=304), electrophysiologic
tests (n=204), blood tests (n=39), imaging (n=211), genetic testing (n=132) and visual
fields (n=127). Forty five have been performing eye movement recording as referrals.
Ninety one do not see nystagmus patients. Three hundred and seven ophthalmologists
wanted orthoptic facilities to be available, 250 wanted electrophysiology, 82 wanted
blood tests, 232 imaging, 188 genetics, 148 visual field. 174 ophthalmologists felt eye
movement recordings would be helpful in the managment of nystagmus
Conclusions: Most ophthalmologists are seeing nystagmus patients. There is a demand
to increase access of eye movement recordings and genetic testing.
CR: I. Choudhuri, None; N. Sarvananthan, None; I. Gottlob, None.
Support: None
2833 - A88
Voluntary Modulation of Involuntary Eye Movements During Reading
2834 - A89
A Study Assessing the Effect of Tenotomy Procedures on Infantile Nystagmus
M.G. Thomas, F.A. Proudlock, R.J. McLean, I. Gottlob. Ophthalmology Group,
University of Leicester, Leicester, United Kingdom.
R.J. McLean, A. Kumar, F.A. Proudlock, I. Gottlob. Ophthalmology Group, University
of Leicester, Leicester, United Kingdom.
Purpose: To understand how individuals with infantile nystagmus read in view of
the sensory motor deficits associated with this condition.
Methods: Eye movement recordings were carried out in healthy (n=7), IIN (n=14) and
albino (n=10) volunteers during reading for distance (1.2m) and near (0.33m) at five
gaze positions (-20°, -10°, 0°, 10° and 20°). Reading speeds (RS) and beating pattern
were derived from these recordings. Visual acuity (VA) was also measured over the
same eccentricities and distances. The nystagmus volunteers underwent a further
fixational task over the same eccentricities to derive the waveform characteristics
of nystagmus.
Results: RS were significantly (p<0.05) slower in nystagmus volunteers when compared
to age and IQ matched controls. VA is a good predictor of RS in IIN (R 2 = 0.48, p<0.05)
but not albinism (R 2 = 0.08, p<0.05). Right beating waveform was associated with
faster RS and left beating with slower RS (p<0.05). Intensity had a significant effect
on RS in IIN (p<0.05); however, it was a poor predictor of RS (R 2 = 0.12). There was a
change in the nystagmus waveform when fixating a target and when reading. During
reading around the null point most volunteers used a pendular waveform which
was modulated by the quick phases while during fixation different waveforms were
encountered. The voluntary modulation of the nystagmus is further substantiated by
the difference in frequency between the fixational task and the reading task.
Conclusion: We describe, for the first time,
that VA is a reliable measure of RS in IIN
but not in albinism. However, intensity
does not predict RS. Therefore oculomotor
recordings and VA measurements should
be supplemented with reading tests to
assess functional visual improvements.
The direction of the fast phase and/or
slow phase significantly affects RS. This
could be because reading is an asymmetric
task; English text reading is from left to
right. Therefore right beating nystagmus fosters faster reading speeds (see figure).
The “controlled” pendular waveform and difference in frequency suggests that these
volunteers are able to modulate their waveform during reading, thus voluntary control
of nystagmus occurs during reading.
CR: M.G. Thomas, None; F.A. Proudlock, None; R.J. McLean, None; I. Gottlob,
None.
Support: NERC foundation, Wolfson foundation & Wellcome foundation
Purpose: To assess the validity of the tenotomy procedure in patients with infantile
nystagmus in terms of visual acuity and nystagmus intensity.
Methods: Eye movements (500Hz) and LogMAR visual acuities were recorded from
6 patients with infantile nystagmus before and after a tenotomy procedure was
performed. Eye movements and visual acuity (VA) were recorded at distance (1.2m)
and near (0.4m) for 4 patients with albinism and nystagmus (1 of which had combined
tenotomy/strabismus surgery) and 2 patients with idiopathic periodic alternating
nystagmus (PAN). Nystagmus intensity was measured at positions from -30° to 30°
eccentricity (for both 1.2m and 0.4m) at 3° intervals along the horizontal plane and the
data was compared before and after (1wk, 4wks, 8wks, 12wks) surgery. Changes in
intensity were viewed at null point and across all positions and compared to changes
in VA. The patients’ own subjective estimates of change in VA and nystagmus were
also recorded.
Results: In terms of LogMAR VA the albinism patients improved by 13.8%, 17.8% and
-3.5% for distance and 15.3%, 14.8% and 12.6% for near. The combination tenotomy/
strabismus patient improved by 3.4% for distance and 18.8% for near. The amount
of improvement appeared to be dependent upon gaze position. Both PAN patients
showed no change in VA. Variable changes were found on eye movement recordings,
particularly reduction of nystagmus intensity on lateral gaze. All patients felt
subjectively that their nystagmus had improved and all but one patient felt they had
an improvement in VA.
Conclusions: Early reports suggest that tentomy may improve infantile nystagmus.
However, it is necessary to evaluate more patients to substantiate these findings and
find which patients respond best to the procedure.
CR: R.J. McLean, None; A. Kumar, None; F.A. Proudlock, None; I. Gottlob, None.
Support: Ulverscroft Foundation
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
2831-2834
Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2827 - 2840 / A82 - A95
323. Nystagmus Organizing Section: EY
2835 - A90
Dynamic Improvements in Visual Function After the Tenotomy and
Reattachment Procedure: Model Predictions and Patient Data
2836 - A91
Investigating the Veracity of a Commercial, Non-Medical, Magnetic
“Treatment” for Infantile Nystagmus Syndrome
L.F. Dell’Osso1,2, Z.I. Wang1. 1Daroff-Dell’Osso Ocular Motility Laboratory, Dept
of Veterans Affairs Medical Ctr and CASE School of Medicine, Cleveland, OH;
2
Neurology and Biomedical Engineering, Case Western Reserve University,
Cleveland, OH.
J.B. Jacobs1,2A, Z.I. Wang1, K. Liao1, L.F. Dell’Osso1,2B. 1Daroff-Dell’Osso Ocular
Motility Lab, Dept of Veterans Affairs Medical Ctr and CASE School of Medicine,
Cleveland, OH; ANeurology, BNeurology and Biomedical Engineering, 2Case
Western Reserve University, Cleveland, OH.
Purpose: Infantile nystagmus syndrome (INS) patients often cannot quickly locate new
visual targets (they are “slow to see”) or visually track moving objects (they cannot
“catch up”). Dynamic demands on visual function are not measured by static measures,
e.g., visual acuity; they require time-sensitive measures. We investigated how the
dynamic properties of INS, saccadic latency (Ls) and both stationary (saccadic) and
pursuit target-acquisition times (Lt), were affected by the tenotomy and reattachment
(T&R) procedure. We used our behavioral ocular motor system (OMS) model to predict
the responses of subjects with INS.
Methods: We compared the pre- and post-T&R responses of 4 INS subjects with
different INS waveforms to test the model’s predictions. Infrared reflection was
used for one INS subject, high-speed digital video for three. We analyzed the human
subjects’ responses to large and small target-step and ramp stimuli. Ocular motor
simulations were performed in MATLAB Simulink and analysis in MATLAB using
OMtools software (downloadable from omlab.org).
Results: Ls values were typically slightly higher than normal and unaffected by
T&R. Saccadic and pursuit Lt values were a function of when in the INS cycle the
moving stimuli occurred and were decreased by the T&R procedure. Model outputs
and predictions accurately simulated human data. During smooth pursuit, stimuli
occurring near intrinsic saccades resulted in steady-state errors in both the predicted
model outputs and patient responses.
Conclusions: Intrinsic saccades disrupt the OMS’ ability to accurately calculate saccade
amplitude and either refoveate or pursue targets. The T&R procedure reduces both
stationary and pursuit target-acquisition times. OMS model simulations predicted
novel stimulus-based effects on both types of target acquisition time in INS. Our
model demonstrated emergent behaviors and predicted the therapeutic effects of
T&R. The dynamics of INS foveation in INS-subject responses to changes in target
position and velocity corresponded to both of the above patient complaints and to
our model predictions.
CR: L.F. Dell’Osso, None; Z.I. Wang, None.
Support: Dept of Veterans Affairs Merit Review
Purpose: Infantile nystagmus syndrome (INS) often leads to reduced visual acuity
because of impaired ability to maintain stable gaze. Although INS cannot be cured,
there are several accepted treatments - surgical, optical, and pharmacological - which
have undergone rigorous scientific study for many years. Recently, advertisements
have appeared for magnetized earrings that have been purported (among other claims)
to improve the vision of people with INS. We cannot dismiss this out of hand, as
(dubious benefits ascribed to “magnetism” aside) this could hypothetically make use
of the same mechanism that we have previously shown to be a major contribution of
contact lenses and other afferent stimulation of the trigeminal nerve (exteroception),
similar to the mechanism (proprioception) hypothesized to underlie the therapeutic
effects of nystagmus surgery.
Methods: We recorded fixation eye movements from five patients with INS, at gaze
angles from 30° left to 30° right, in 5° increments. Data were sampled at 500 Hz,
using digital video. Subjects were calibrated monocularly to determine alignment
and viewing eye(s), and tested under four conditions: baseline, clip-on earring,
purpose-sold magnet earring, and high-strength, rare-earth magnets. The patients
were not told the significance of each testing condition prior to the recording session.
We used the expanded Nystagmus Acuity Function (NAFX) to analyze the foveation
characteristics of nystagmus waveforms and thereby determine best potential visual
acuity under each test condition.
Results: Gross visual inspection of the nystagmus waveforms showed no difference
between the control condition and the other trials for any subject. No subject reported
any perceptual difference between the four conditions, either visual or how their
nystagmus “felt.” NAFX analysis did not show significant differences between the
control and any of the three ear-stimulus conditions.
Conclusions: Although a previous study reported positive results (reduced nystagmus)
following application of magnetic earrings, the findings are questionable as there were
not sufficient control or alternative testing conditions, nor was a rigorous analysis of
the nystagmus waveform performed using a quantitative, foveation-based method.
Instead, findings relied on patient reporting, and a visual acuity exam that may
have been affected by other factors. Correcting for these factors, no demonstrable
improvements in the subjects’ nystagmus was found.
CR: J.B. Jacobs, None; Z.I. Wang, None; K. Liao, None; L.F. Dell’Osso, None.
Support: VA Merit Review
2837 - A92
Eye Muscle Surgery for Infantile Nystagmus Syndrome (INS) in the First Two
Years of Life
2838 - A93
Convergence Dampening of Infantile Nystagmus Syndrome and its
Relationship to Heterophoria
R.W. Hertle1, J. Felius2, D. Yang1, M. Kaufman 3. 1Ophthalmology, Childrens Hospital
of Pittsburgh, Pittsburgh, PA; 2Department of Ophthalmology, University of Texas
Southwestern Medical Center, Retina Foundation of the Southwest, Dallas, TX;
3
Ophthalmology, Childrens Hospital of Pittsburgh, The University of Pittsburgh
School of Medicine, PA.
R.P. Rumpf, Z. Tai, R.W. Hertle, D. Yang. Ophthalmology, The Ocular Motor
Neurophysiology Laboratory, The UPMC Eye Center, Department of
Ophthalmology, The Children’s Hospital of Pittsburgh and The University of
Pittsburgh, Pittsburgh PA 15213, Pittsburgh, PA.
Purpose: We characterize the effects of eye muscle surgery in a young cohort of
patients with INS.
Methods: This is a prospective, comparative, interventional case series of 19 patients.
All had an associated head posture or strabismus. All had two virgin recti on each
eye operated on with some having a superior or inferior oblique muscle surgery for
a chin up or down posture. All patients were followed for a minimum of 12 months.
Outcome data and measures were obtained clinically with Teller acuity testing and
with eye movement recordings and included: demography, associated eye/systemic
conditions and Pre- and Post-Operative; Binocular Best Corrected Teller Acuity (BCTA),
Anomalous Head Posture (AHP), Strabismic Deviation (SD), null zone width (NZW)
and Nystagmus Optimal Foveation Fraction (NOFF), absolute foveation time (FOV)
and null zone waveform changes (NZW).
Results: Patients ranged in age from 5-23 mos (ave 17.4 mos), follow up averaged 14.0
mos, 8 had associated systemic disease, preoperative head postures in 13 (68%) ranged
from 15 to 35 degrees. The most common associated ocular conditions were strabismus
in 15 (79%), ammetropia in 13 (68%), and amblyopia in 9 (47%) and optic nerve, foveal
or generalized retinal disease with or without albinism in 15 (79%). Regardless of
the amount of head posture in degrees, after surgery, all patients significantly (p <
0.05) improved in AHP. There were significant (p <0.05) improvements, SD, NOFF.
FOV and NZW. Group mean BCTA significantly improved (p<0.03). There were
none who required a second operation and only a conjunctival suture related cyst
occurred in two eyes.
Conclusions: This study provides
evidence that extraocular muscle
surgery in the first two years of life in
patients with INS waveformsfavorably
changes their head posture, vision and
nystagmus characteristics. Thus adding
further evidence that eye muscle surgery
positively affects the oscillation of INS
and subsequent function
CR: R.W. Hertle, None; J. Felius, None; D. Yang, None; M. Kaufman, None.
Support: FFS PED0403
Purpose: Convergence dampening (CD) is often observed in patients with Infantile
Nystagmus Syndrome (INS). However, it is not clear why it occurs only in some of
the patients and not in others. To better understand the mechanism of the CD, we
investigated the relationship between the CD and heterophoria in two groups of
patients with and without CD.
Methods: Six INS patients were recruited. Eye movements were measured using a
video-based eye tracking system (EyeLink 1000 desktop). First, the CD was identified in
a near/far viewing paradigm where patients alternatively looked at two targets, one at
30 cm and the other 150 cm from the eyes. The alternate duration was 5 seconds. Then
heterophoria for each patient was measured using an alternate cover test in a fixation
paradigm where patients fixated on a 0.5 degree target at 150 cm for one minute. The
relationship between heterophoria and CD was analyzed with relation to visual acuity,
binocular function and degree of clinically observed heterophoria.
Results: Of the six patients recruited, five showed horizontal heterophorias and are
listed in group A and one patient who did not show any heterophoria was put into
group B. In group A, 100% of patients demonstrated an observable change in eye
movements, as evidenced by eye movement recordings, with either convergence or
divergence. Of these five patients, 3 showed convergence dampening and 2 showed
divergence dampening. In contrast, CD was not obvious in group B.
Conclusions: The presence of a heterophoria seems to contribute to the CD although
other central neural mechanism may be involved.
CR: R.P. Rumpf, None; Z. Tai, None; R.W. Hertle, None; D. Yang, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
2835-2838
Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2827 - 2840 / A82 - A95
323. Nystagmus Organizing Section: EY
2839 - A94
A Novel Mutation of the FRMD7 Gene in an Indian Family with X-linked
Congenital Nystagmus
2840 - A95
Ferm Domain Containing 7 (frmd7) Expression in Developing Murine Tissues
B. Chhunchha1A, R. Singh2, R.V. Mandava1B, S.K. Nath 3, U. Ratnamala4, U. Radhakrishna4.
A
Department of Zoology, BZoology, 1School of Sciences, Gujarat University,
Ahmedabad, India; 2Dr. P.L. Desai Eye Center, Ahmedabad, India; 3Arthritis and
Immunology Research Program, Oklahoma Medical Research Foundation, 825
N.E.13th Street, Oklahoma City, OK; 4Cancer centre, Creighton University, Omaha,
NE.
Purpose and Methods: Congenital nystagmus (NYS) is characterized by bilateral,
and uncontrollable, involuntary movement of the eyes; its frequency is ~1:1500 live
births. It is one of the most common neuro ophthamalological disorders among live
births, and also reduces visual acuity. Nystagmus is transmitted in X-linked dominant,
X-linked recessive and autosomal dominant forms with high penetrance and variable
expressivity. Four NYS genomic locations (NYS1, NYS2, NYS3 and NYS4), mapped to
Xq26.2, 6p12, 7p11.2 and 13q31-q22 respectively using family-based linkage analysis
have been documented. Very recently, ~30 mutations of the FRMD7 gene, which maps
to Xq26.2 region, have been found in NYS patients, suggesting that this gene plays an
important role in the NYS development.
Results & Conclusions: We report a novel mutation of the FRMD7 in a large elevengeneration Indian pedigree with an isolated non-syndromic NYS in which 62 members
affected by NYS with different phenotypic expression including asymmetric pendular
eye movements with unidirectional jerky NYS and head nodding. The missense
mutation, c.A917G, predicts a substitution of Arg for Gln at codon 305 (Q305R) within
exon 10 of FRMD7. This mutation was found to be at a highly conserved residue within
the FERM adjacent (FA) domain, hypothesized to have a regulatory function, based
on similarity to other protein kinase substrates. A detailed data of the present family
and mutation spectrum of FRMD7 gene will be presented.
CR: B. Chhunchha, None; R. Singh, None; R.V. Mandava, None; S.K. Nath, None; U.
Ratnamala, None; U. Radhakrishna, None.
Support: None
T.E. Preston1, J. Self 1, H.M. Haitchi2, X. Chen1, A. Lotery1. 1Clinical Neurosciences,
Clinical Neurosciences Division, Southampton, United Kingdom; 2Division of
Infection, Inflammation and Repair, Roger Brooke Laboratory, Southampton
University, United Kingdom.
Purpose: To assess the temporal expression profile of the FRMD7 gene during the
development of murine brain, lung and heart tissue.
Background: Mutations in the FRMD7 gene are known to cause some cases of
Congenital Idiopathic Nystagmus (CIN). Little is known about the pathophysiology
of CIN or the function of this gene. Studies have indicated very low levels of gene
expression in most human tissues with highest levels found in kidney.
Results obtained using in situ hybridization have localized some expression to
structures in the developing human embryonic brain. Funding for this research
wasmade possible by the Nystagmus Network and the Gift of Sight appeal.
Methods: Heart, lung and brain tissues were obtained from MF-1 mice at 11
developmental time points between embryonic days 11 and post natal day 8 and
from adult mice. cDNA was extracted from these tissues and the relative expression
of mRNA was calculated using quantitative real-time PCR techniques with GAPDH
and ACTB normalising genes.
Results: Expression of FRMD7 was found to be low in all three tissues with no
significant variation seen in heart and lung tissues between ED11 and PD8, although
there was a significant rise in the adult samples. However a significant increase was
observed at ED18 in brain tissue.
Conclusion: An increase in the expression of FRMD7 mRNA was seen at ED18 in
murine brain contrasting with low level expression in heart and lung samples. Genes
expressed during murine brain development are known to show temporal functioning
clustering so it is possible to compare this expression profile with other genes and
gene clusters expressed in the developing murine brain. Genes involved in formation
and function of synapses and axon growth and guidance show the same temporal
pattern as FRMD7 mRNA suggesting a similar role for the FRMD7 protein. These
results suggest potential candidates for protein-protein interaction studies. They also
help direct future work using an antibody to the FRMD7 protein.
CR: T.E. Preston, None; J. Self, None; H.M. Haitchi, None; X. Chen, None; A.
Lotery, None.
Support: Nystagmus Network and Gift Of Sight Appeal
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
2839-2840
Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81
325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY
2873 - A58
Eye Movement Responses to Unilateral and Bilateral Otolithic Stimulation
From Bone Conducted Sound
2874 - A59
Effects of Callosotomy on Nasotemporal Smooth Pursuit in Macaque Monkey:
Validating a Cerebral Gaze Asymmetry Mechanism
E.D. Cornell1A, A. Burgess1B, H.G. MacDougall1B, I.S. Curthoys1B. AFaculty of Health
Sciences, BFaculty of Science, 1University of Sydney, Sydney, Australia.
L. Tychsen1A, D. Sarezky1B, J. Leonard1C, P. Foeller1A. AOphthal and Neurobio-Childrens
Hosp, BOphthalmology, CNeurosurgery, 1Washington Univ Schoof of Medicine, St
Louis, MO.
Purpose: Air conducted sound (ACS), delivered through headphones, and bone
conducted vibration (BCV) of the head stimulate otolithic receptors in the inner
ear and can evoke short latency vestibular induced extraocular muscle potentials
(oVEMPs) recorded by electrodes beneath the eyes, that peak at approximately 10
ms. Studies using scleral search coils have confirmed, in a few subjects, the presence
of small predictable eye movements following very short duration ACS and BCV.
We sought to test whether longer duration BCV stimuli delivered to the mastoids
unilaterally and bilaterally induced consistent eye movements and the effect of eye
position on the movement.
Methods: Bone conducted tone bursts at 500Hz with a duration of 150 ms and an
inter-stimulus interval of 900ms were delivered at the mastoid unilaterally and
bilaterally to healthy subjects using B71 bone conductors that were held in place by a
latex cap while the subject’s eyes were directed to various positions. The resulting eye
movements were recorded using 250Hz high resolution fire wire cameras.
Results: A very small response at 10ms post stimulus could be detected in some
subjects that was consistent with previous oVEMP responses. However this was
followed by a much larger and more sustained response. Eye movements following
unilateral stimulation were up to 0.35o (vertical) and 0.26o (horizontal), with a latency
of around 25ms and with peak amplitudes at approximately 125ms post stimulus. The
stimulus caused eye elevation for fixation positions towards the stimulated mastoid
and depression for fixation positions opposite the stimulated mastoid. Horizontal
responses were towards the stimulated mastoid. With bilateral stimulation the
response was effectively a summation of unilateral movements: the vertical component
increased (up to 0.57o) and the horizontal component was reduced or eliminated.
Conclusions: Bone conducted vibration to the otoliths produces predictable horizontal
and vertical conjugate eye movements that are gaze position dependent.
CR: E.D. Cornell, None; A. Burgess, None; H.G. MacDougall, None; I.S. Curthoys,
None.
Support: None
2875 - A60
Effects of Earth-Fixed vs Head-Fixed Target on Ocular Counterroll
M. Chandrakumar, Z. Hirji, A. Blakeman, H. Goltz, G. Mirabella, A. M. Wong.
Ophthalmology and Vision Sciences, The Hospital for Sick Children and University
of Toronto, Toronto, ON, Canada.
Introduction: Ocular counter-roll (OCR) generates compensatory torsional eye
movements during static head tilt. OCR is important from a clinical standpoint,
because it explains the abnormal compensatory head tilt in patients with trochlear
nerve palsy, and it forms the basis of the Bielschowsky head-tilt test. However, Jampel
and Shi1 challenged the existence of OCR. One possible explanation for their1 failure to
detect any OCR response may be their use of a head-fixed target. When a target moves
with the head, the vestibulo-ocular reflex (VOR), including OCR, must be nulled to
stabilize the target image on the fovea. The purpose of this study was to investigate
whether OCR gain is reduced during viewing of a head-fixed target, as compared to
an earth-fixed target, in healthy subjects.
Methods: Twelve normal subjects were recruited. The target consists of a central
fixation cross against a high-contrast grid pattern at 33 cm. The target was mounted
on a vertical wall (earth-fixed), or coupled to the head (head-fixed). Eye movements
were recorded using a video-based system. Changes in mean torsional eye position
were plotted as a function of head position steps (0±25 deg in 5 deg steps) and fiveparameter sigmoidal fits were performed. Mean OCR gains were calculated by taking
the derivative of the fitted functions.
Results: Mean OCR gain with a head-fixed target (-0.084) was 40% lower than that
with an earth-fixed target (-0.141; p < 0.0001).
Conclusion: The partial decrease in OCR gain during viewing of a head-fixed target
indicates that OCR is suppressed when a target moves with the head. This OCR gain
reduction may result from suppression of the VOR by a central process.
References: 1. Jampel RS, Shi DX. The absence of so-called compensatory ocular
countertorsion: the response of the eyes to head tilt. Arch Ophthalmol 2002; 120:
1331-1340.
CR: M. Chandrakumar, None; Z. Hirji, None; A. Blakeman, None; H. Goltz, None; G.
Mirabella, None; A. M. Wong, None.
Support: MSH 55058, MOP 152588 and MOP 57853
Purpose: Knowledge to date regarding horizontal gaze control in primates indicates
that smooth eye tracking is driven by neurons in the medial-superior-temporal (MST)
area of each cerebral hemisphere. The directional organization is ipsiversive: MST
of the right hemisphere drives rightward tracking and MST of the left hemisphere,
leftward tracking. Visual motion neurons of areas V1/MT must send feed forward
projections--representing rightward vs. leftward motion from each visual hemi
field--to the appropriate MST, presumably through the splenium (posterior quarter)
of the corpus callosum. Convolving visual hemi fields on rightward vs. leftward
motion, callosotomy would be expected to disrupt tracking of stimuli moving away
from the vertical meridian within each hemi field (centrifugal motion), but spare
tracking of stimuli moving toward the vertical meridian (centripetal motion). To test
this prediction, we performed a partial callosotomy.
Methods: The splenium (i.e. posterior portion) of the callosum was sectioned in a 1
yr old monkey. The rostrum, genu and body of the callosum were left intact. Several
weeks later, horizontal step-ramp motion stimuli were confined to the right or left
visual hemi fields to elicit centripetal vs. centrifugal smooth pursuit when viewing
with either eye monocularly.
Results: Smooth eye velocity evoked by ramps of stimulus motion revealed decrements
in gain of ~ 20% for centrifugal motion within each hemi field. The response to
centripetal motion was unaffected. Latencies for centrifugal motion were prolonged
(~20%) when compared to those for centripetal motion. Saccadic latency and accuracy
was unaffected.
Conclusions: Sectioning of the callosal splenium produced the predicted asymmetry
of pursuit, but the effect was underwhelming. Two interpretations are possible: 1) the
sectioning may have been less complete than assumed, or 2) visual projections from
areas V1/MT travel through more anterior regions of the callosum (e.g. the body as
well as the splenium). Further experiments will be necessary to establish the validity
of these interpretations.
CR: L. Tychsen, None; D. Sarezky, None; J. Leonard, None; P. Foeller, None.
Support: NIH Grant EY10214 (LT,PF)
2876 - A61
The Effect of Amplitude and Interval on Ocular Torsion When Viewing
Rotating Images
U. Sverkersten, G. Öqvist Seimyr, T. Pansell, S. Abdi, J. Ygge. Department of Clinical
Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Purpose: When an image containing spatial information is tilted, it induces more
compensatory ocular torsion than an image without spatial information (Pansell,
Sverkersten & Ygge, 2006). The aim of the present study was to investigate the effect
of amplitude (of image rotation) and interval (image rotation frequency) on visually
induced ocular torsion.
Methods: Ocular torsion was recorded in five healthy individuals using a head
mounted video oculography system (Chronos vision, Germany). The stimulus
consisted of an image showing a city scene rich in spatial orientation cues. Centered
on the image was a fixation point which the subject was instructed to look at. The
stimulus was displayed on a computer screen (1600x1200 @ 60Hz) at a distance of 50
cm. After ten seconds, the image started to rotate (clockwise) around the fixation point
in steps of 3.75°, 7.5° or 15° at intervals of 1.5, 3 or 9 seconds. The image continued to
rotate in steps for 60 seconds. The rotations had a smooth acceleration and deceleration
phase and lasted one second. All subjects viewed all combinations of amplitudes and
intervals in a randomized order. Between each of the nine conditions there was a
washout period when nothing was displayed on the screen for 30 seconds.
Results: An immediate transitory torsional response was found for each stimulus
rotation. The 15 degree amplitude induced a larger transient response (2.40± 0.16 deg)
compared to the 7.5-degree (1.8±0.19 deg) and the 3.75-degree (1.38±0.12 deg) rotations.
In the tests with short time intervals, the torsional position was accumulated over
time, shifting the torsional position in the same direction as the stimuli (maximum
5 deg). In the tests with longer time intervals the torsional position returned towards
the initial reference position before the next stimuli took appeared.
Conclusions: A larger stepwise rotation induced a larger torsional response. The time
interval between rotations had little influence on the transient torsional response.
However, a short time interval induced a shift of the torsional position, something
which was not seen at longer time intervals.
CR: U. Sverkersten, None; G. Öqvist Seimyr, None; T. Pansell, None; S. Abdi,
None; J. Ygge, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
2873-2876
Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81
325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY
2877 - A62
Ocular Torsion and Associated Head Movement in a Flight Simulator
2878 - A63
Test-Retest Reliability of Saccadic Measures
S. Gowrisankaran, N. Fogt. Vision Science, Ohio State University, Columbus, OH.
T.M. Blekher1A, M.R. Weaver1B, J. Marshall1B, J. Wojcieszek1C, L. Flury-Wetherill1B,
R.D. Yee1A, T.M. Foroud1B. AOphthalmology, BMedical and Molecular Genetics,
C
Neurology, 1Indiana University School of Medicine, Indianapolis, IN.
Purpose: In previous studies, head tilt in the direction of a tilting horizon has been
demonstrated in a flight simulator. Torsional eye movements during movement of the
horizon in a flight simulator have not been examined. The purpose of this study was to
measure ocular torsional responses to a moving horizon in a static flight simulator.
Methods: 5 subjects (18-35 yrs) participated. Subjects viewed a projected scene (of the
sky and the ground) in a dark room. Eye and head movements were recorded using
a video tracker and a magnetic sensor respectively. 10 trials were recorded for each
subject. In each trial subjects tilted the airplane/horizon (using a joystick) randomly
to the right or left away from the horizontal meridian (aligning tilt), and returned the
plane to a non-tilted horizontal position (realigning tilt). The movement of the horizon
was recorded. The average frequency of these sinusoidal movements was 0.3 Hz.
Results: 3D eye and head movements for 20 blink free (20 aligning and 20 realigning
tilts) trials were analyzed. The average magnitude of aligning tilt was 48deg and
was 55deg for the realigning tilt. An ocular torsional response occurred with tilt of
the horizon in 32 out of 40 cases. Head tilts (always in the direction of horizon tilt)
occurred in 28 of the 40 cases analyzed. The average head tilt was 11.7deg for the
aligning tilt and 8.7deg for the realigning tilt. Regardless of whether the head moved
the typical torsional response was a high velocity movement in the same direction
and faster than the horizon tilts, with an amplitude gain of 0.07. This was followed
by a drift opposite to the initial movement. The average fast phase amplitude was 3.9
deg (aligning tilt), and 3 deg (realigning tilt).
Conclusion: Small, high velocity torsional eye movements occurred in the direction
of horizon tilt with and without head movements. These torsional eye positions
were not sustained. If ocular counter-roll occurred with head movement, it did not
completely cancel the high velocity torsional movement. In a static flight simulator,
individuals make high velocity torsional movements in the direction of horizon tilt
that are different from the following responses generated in previous studies in
response to full-field torsional rotation of the visual scene.
CR: S. Gowrisankaran, None; N. Fogt, None.
Support: Naval Aerospace Medical Research Laboratory
2879 - A64
Cortical Areas Involved in Vertical Saccades With a 3 Teslas Functional Mri
J. Beynat1A, S. Bidot1A, P. Quercia1A, F. Ricolfi1B, T. Pozzo2, A.M. Bron1A, C. CreuzotGarcher1A. ADepartment of Ophthalmology, BDepartment of Neuroradiology,
1
University Hospital, Dijon, France; 2Inserm u887, University of Burgundy, Dijon,
France.
Purpose: The aim of this study was to assess the activation of the cortical eye fields
involved in vertical and horizontal saccades with a 3 teslas functional MRI.
Methods: Eight healthy right-handed subjects (6 men and 2 women) participated
in the study. The tasks tested 2 different types of saccades: “visually guided” and
voluntary. For each one, we compared cortical eye fields activation during vertical
axis eye movements with those activated during horizontal axis movements. The
acquisition of the data was carried out via the Neuro 3D software (Siemens, Germany).
Statistic data treatment was carried out using FSL software (FMRIB Software Library)
according to the General Linear Model (GLM). The analysis of the pictures was done
with MRIcro software (v 1.4, Chris Rorden, the United Kingdom).
Results: Picture analysis was realized with the group analyses maps, and with
the substraction maps. For each type of saccades, we could find the activation of
most cortical areas involved in eye movements; the Frontal Eye Field (FEF), the
Supplementary Eye Field (SEF) and the Posterior Parietal Cortex (PPC). An activation
of the superior parietal cortex (7th Brodmann area) was observed for both types of
vertical saccades. In addition, we found a specific activation of the right DorsoLateral
PreFrontal Cortex (DLPFC) during voluntary vertical saccades.
Conclusions: Our study allowed to identify the various activated cortical eye fields
according to the saccades direction. The superior parietal cortex and the DLPFC seem
to be particularly involved during vertical saccades.
CR: J. Beynat, None; S. Bidot, None; P. Quercia, None; F. Ricolfi, None; T. Pozzo,
None; A.M. Bron, None; C. Creuzot-Garcher, None.
Support: None
Purpose: Abnormalities in saccades appear to be sensitive and specific biomarkers
in the pre-diagnostic stages of Huntington disease (HD) The goal of this study was
to evaluate test-retest reliability of saccadic measures in prediagnostic carriers of the
HD gene expansion (PDHD) and normal controls (NC).
Methods: The study sample included 12 NC and 9 PDHD who completed two study
visits within an approximately one month interval. At the first visit, all participants
completed a uniform clinical evaluation. A high resolution video-based system was
used for recording eye movements during completion of the battery of visually
guided, anti-saccade, and three memory guided tasks. Measures of the saccades
(latency, velocity, gain, and percentage of error saccades) were quantified. Test-retest
reliability was evaluated by calculating the intraclass correlation (ICC) of the saccade
measures collected at the first and second visits. Additionally, regression analysis was
used to evaluate the influence of age, gender, and group (NC or PDHD) on difference
in measures between visits.
Results: Percentage of error saccades showed good test-retest reliability in antisaccade and memory guided tasks (average ICC=0.8, p<0.001). The latency of saccades
also demonstrated good test-retest reliability (averaged ICC=0.74, p< 0.02) across all
tasks. The velocity and gain of saccades showed moderate reliability (ICC~0.5). ICC
was similar in NC and PDHD groups for most measures. There were no significant
group, age, or gender effects when analyzing the difference in each saccade measure
between the first and second visit.
Conclusions: Good test-retest reliability of saccadic latency and percentage of errors
in anti-saccade and memory guided tasks suggests that these measures could serve
as potential biomarkers to evaluate progression in HD.
CR: T.M. Blekher, None; M.R. Weaver, None; J. Marshall, None; J. Wojcieszek,
None; L. Flury-Wetherill, None; R.D. Yee, None; T.M. Foroud, None.
Support: R21NS060205, the CHDI Foundation, and an unrestricted Grant from RPB,
Inc. to the Department of Ophthalmology, IU Medical School.
2880 - A65
Saccades and the Muller-Lyer Illusion: Effect of Previews and Saccade
Inhibition
P.C. Knox. Orthoptics, University of Liverpool, Liverpool, United Kingdom.
Purpose: Saccade amplitude is modified by the Muller Lyer (ML) illusion in the same
manner and to the same extent as perception, even when pointing is not affected
(Bernadis et al, 2005, Exp Brain Res 162:133). This is contrary to the predictions of the
“two visual systems” hypothesis. However, the type of saccade, display characteristics
and subject instructions, all play a role in the size of effects observed. Here, the effect
of the ML illusion on saccade amplitude, in circumstances in which subjects had to
suppress reflexive responses, was investigated with two display times (200ms and
1000ms).
Methods: Twelve subjects were exposed to ML displays with one vertex at fixation and
the other displayed eccentrically to left or right (6° separation between vertices). “In”
(><), “out” (< >) and control (xx) configurations, direction and display time (200ms vs
10000ms) were interleaved. Subjects were instructed not to saccade until the display
was extinguished. Eye movements were recorded with infrared oculography and
primary saccade amplitude and latency measured offline. Only saccades with a latency
from target offset of >100ms and an amplitude >3° were included in the analysis.
Results: Two subjects’ data were not analysed for technical reasons. For both display
times, the remaining 10 subjects suppressed reflexive saccades, and responded to
the target offset, at the cost of increased latency (time from offset, 200ms: latency =
381±45ms; 1000ms: 305±40ms; t=4, p<0.0001; Fig A). For both display times, saccade
amplitudes increased with the “in” and decreased with the “out” configuration.
Effect size calculations (In-Out/Control, expressed as %) showed a trend towards
larger effects with the 1000ms display time (200ms: 18±5% vs 1000ms:23±9%; t=1.6,
p=0.06; Fig B).
Conclusions: Saccade amplitude was modified by the ML illusion, in the same manner
and to a similar extent, as perception in these experiments. The effect of an extended
preview period was to decrease saccade latency, and increase illusion effect size.
However, the effect sizes were similar to what we have reported previously for both
reflexive and memory guided saccades (Knox & Bruno, 2007, Exp Brain Res 181:277).
These results are not compatible with any strong version of the two visual systems
hypothesis.
CR: P.C. Knox, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
2877-2880
Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81
325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY
2881 - A66
Fourier Transformation Reveals a New Fixational Eye Movement
2882 - A67
Effects of Caffeine on Fixational Eye Movements
B. Zhang1, T. Pansell1, J. Ygge1, S. Giovagnoli2, R. Bolzani2. 1Department of Clinical
Neuroscience, Karolinska Institutet, Stockholm, Sweden; 2Department of
Psychology, University of Bologna, Bologna, Italy.
N.E. Collins1,2A, M. AlKalbani2A,1, P. Kavanagh 3, A. Mahmud 3, G. Boyle2B, D. Coakley2A,1.
1
Medicine, Trinity College Dublin, Dublin 2, Ireland; AMercer’s Institute for
Research on Ageing, BMedical Physics and Bioengineering, 2St James’s Hospital,
Dublin 8, Ireland; 3Dept. of Pharmacology and Therapeutics, Trinity Centre for
Health Sciences, St James’s Hospital, Dublin 8, Ireland.
Purpose: A slow periodic oscillation of the eye position occurring during visual
fixation has been identified. To our knowledge, this type of eye movement has not
been described before. The aim was to describe its characteristics.
Methods: Eye movements were recorded binocularly in six healthy subjects. In test
1 the effect of three different recording techniques was analyzed: infrared corneal
reflection technique with head mounted goggles (XY1000, IOTA Inc.); head mounted
video oculography (VOG; Chronos Vision); and Scleral Search Coil (SSC: Skalar
Inc.). In test 2 the effect of sampling frequency was evaluated by using the SSC with
different sampling frequencies (120, 140, 160, 180 and 200 Hz). The eye position data
was band-pass filtered (0.05-0.15) and the oscillatory components of the eye position
were evaluated by a fast fourier transformation (FFT).
Results: A consistent finding in all test subjects and recordings was a slow periodic
oscillation of eye position i.e. the eye position oscillated (amplitude ±0.5 deg) in
a horizontal-vertical elliptical track. The duration of a complete oscillation was
approximately 10 seconds. The FFT analysis thus revealed an prominent peak value
(~0.1 Hz) with large intra-individual variation but small inter-individual variation,
independent of recording technique, sampling frequency or related to blinking.
Conclusion: A slow regular oscillation of eye position was demonstrated which does
not seem to be an artefact due to recording technique, sampling frequency or blinking.
The finding advocates new thoughts of the visual fixation mechanisms . The purpose
of this new eye movement can at present not be explained but it might be involved in
a light energy protective mechanism of the fovea.
CR: B. Zhang, None; T. Pansell, None; J. Ygge, None; S. Giovagnoli, None; R.
Bolzani, None.
Support: None
2883 - A68
Oculomotor and Vestibular Performance in Children With Autism Spectrum
Disorder.
Purpose: To investigate the acute effect of caffeine on fixational eye movements (ocular
microtremor and microsaccades). Ocular microtremor (OMT), a minute eye movement
present at all times in normal subjects, is a measure of arousal in terms of reticularformation activity, and has been demonstrated as a potential measure of brainstem
integrity in multiple sclerosis, coma and brainstem death. Drugs which alter arousal
and alertness may affect OMT, and confound its measurement in the clinical setting.
We investigated whether the common stimulant caffeine affects OMT, and whether
it is a source of variability in studies of fixational microsaccades.
Methods: The effect of a single oral dose of caffeine on ocular microtremor was
examined in a randomised double-blind crossover study. Twenty healthy subjects were
studied on two occasions at least a week apart, after ingestion of 350ml caffeinated
(180mg) and decaffeinated (< 10mg) coffee, in randomized order. OMT recordings were
made using the piezoelectric strain-gauge technique, at baseline, and at 30 minutes
and 90 minutes after coffee ingestion.
Results: Compared with baseline, there was a small but significant increase in OMT
peak frequency at 30 minutes after caffeine ingestion from 85.9Hz (SD 3.4Hz) to
87.9Hz (SD 3.3) (95% CI for difference between means: 1.0Hz, 3.0Hz; p < 0.001). OMT
frequency remained slightly elevated at 90 minutes after caffeine ingestion. No
effect was seen with decaffeinated coffee. There was also a trend towards fewer
microsaccades following caffeine ingestion, from 49.6 microsaccades/min at baseline
to 36.2 microsaccades/min at 30 minutes, (95% CI for difference between means: -3.4,
30.2), although this did not reach significance (p = 0.111).
Conclusions: The results demonstrate that the frequency of OMT is increased in
response to caffeine. The increase in OMT frequency was relatively small, and not
clinically significant in the context of previous studies of OMT. In studies of fixational
eye movements where small differences in parameters are considered significant,
caffeine should be taken into account as a potential source of variability.
CR: N.E. Collins, None; M. AlKalbani, None; P. Kavanagh, None; A. Mahmud,
None; G. Boyle, None; D. Coakley, None.
Support: None
2884 - A69
Eye Movements Disorders in Glaucoma
J.O. Phillips1A,2, D.E. Parker1A, C.M. Jacobs2, R.J. Groen1B, A.H. Weiss2, S.J. Webb1B.
A
Otolaryngology, BPsychiatry and Behavioral Sciences, 1University of Washington,
Seattle, WA; 2Ophthalmology, Seattle Children’s Hospital, Seattle, WA.
Purpose: A number of authors have hypothesized a relationship between cerebellar
functioning and autism. Some studies have shown correlated changes in oculomotor
behavior. This study compares the conjugate eye movements of children with autism
spectrum disorder with those of normal age-matched controls.
Methods: Children with autism spectrum disorder (ASD, n=13) and typical age
matched control children (TYP, n=23) were tested on a range of eye movement tasks
at Seattle Children’s Hospital. The average age of the subjects was 10.4 y. Subjects were
assessed while holding gaze in the dark, fixating stationary point targets at different
eccentricities, making saccades to pseuorandomly presented point targets, making
sequential saccades to stationary targets in a patterned array, making anti-saccades,
pursuing a sinusiodally moving point target, viewing a moving high-contrast full field
grating (OKN), and during en-block rotation about a fixed vertical axis in the dark
(VOR). Eye movements were recorded binocularly with an SMI videonystagmography
system. All subjects were given the same instruction.
Results: With three notable exceptions, ASD children had stable gaze holding in the
dark and during fixation of eccentric targets. Saccades to stepped targets were highly
variable in a subset of the ASD children, with many showing hypometric saccades
of long duration. Smooth pursuit was variable overall, but ASD children on average
had remarkably good pursuit performance. OKN was abnormal in ASD children only
at higher target velocities. VOR had normal gain in most ASD children. The most
dramatic differences were seen in the sequential saccade task and the antisaccade
task. Children with ASD had consistently poorer performance than TYP children,
despite demonstrating a clear understanding of the task.
Conclusions: Taken together these results show clear differences between ASD and
TYP oculomotor performance in children. However, the remarkably well-preserved
smooth pursuit performance is not entirely consistent with cerebellar models of
ASD.
CR: J.O. Phillips, None; D.E. Parker, None; C.M. Jacobs, None; R.J. Groen, None; A.H.
Weiss, None; S.J. Webb, None.
Support: NAAR (Webb)
C. Lamirel1,2, D. Milea 3, I. Cochereau4, M.H. Duong5, J. Lorenceau2. 1Ophthalmology,
Centre Hospitalier Universitaire, Angers, France; 2Laboratoire de science
cognitive et d’imagerie cérébrale, CNRS, Paris, France; 3Ophthalmology, Glostrup
Hospital, Copenhagen, Denmark; 4Ophthalmology, Hopital Bichat, Paris, France;
5
Ophthalmology, Fondation Ophtalmologique Adolphe de Rothschild, Paris,
France.
Purpose: To investigate disorders of eye movements in open angle glaucoma.
Methods: Comparative study of saccades, pursuit and a saccade-pursuit sequence on
a moving target in 3 groups: 4 patients with open angle glaucoma and a mild visual
field defect (mean MD: -5dB, mean age: 51years); 4 patients with open angle glaucoma
and an almost normal visual field (mean MD: -0.5dB, mean age: 57 years); and 4
age-matched control subjects (mean age: 54 years). Eye movements were recorded
monocularly (right eye for all subjects) at 240hz using an ISCAN ETL-400 system
(Burlington, MA, USA).
Results: For the saccade task, the mean saccade latency was longer in glaucomatous
patients (247 and 259 ms) than in the control group (236ms) (F(2,798)=18, p<10 -3). Mean
saccade gain was lower in glaucomatous patients with visual field defect (81%) than
in patients with almost normal visual field (86%) and in controls (89%) (F(2,798)=13 ;
p<10 -3). During pursuit, maximum eye speed was faster in both groups of patients (31
et 28°/s) than in controls (21°/s) (F(2,2455)=68, p<10 -3). The mean pursuit and gain was
similar in the 3 groups (105% for controls, 107% for normal visual field patients, 110%
for patients with visual field defect) but speed variability of pursuit was larger in the
2 groups of glaucomatous (10 and 9°/s) than in controls (3°/s) (F(2, 2455)=18, p<10 -3).
During the saccade-pursuit task the latency of the maximum’s speed of the saccade
was longer in the 2 groups of patients (305 and 350ms) than in controls (283ms) (F(2,
1910)=103, p<10 -3). Saccade gain was smaller in glaucomatous patients (73 and 75%)
than in controls (82%) (F(2, 1910)=23, p<10 -3). Speed variability of pursuit following
the saccade was larger in glaucomatous patients (7 and 8°/s) than in controls (3°/s)
(F(2, 1910)=54, p<10 -3).
Conclusions: The larger variability and inaccuracy of eyes movements in glaucomatous
patients suggest an alteration of eye movement control in this condition. These patients
had lower performances in the saccade-pursuit task, which required analysis of the
target speed in the peripheral visual field. Glaucoma also affects high order visuomotor functions, even if visual fields are preserved; suggesting that eye movements
may be affected early in the disease
CR: C. Lamirel, None; D. Milea, None; I. Cochereau, None; M.H. Duong, None; J.
Lorenceau, None.
Support: Fondation pour la Recherche Medicale, Fondation Berthe Fouassier,
Fondation de France
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
2881-2884
Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81
325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY
2885 - A70
A New Scalable Computerized Random Dot Stereopsis Test
2886 - A71
The Distance Randot ® Stereotest Test: Normative Data and Validity
R. Robilotto, G. Zikos, A. Selenow, S. Slotnick. Institute for Vision Research,
Manhattan Vision Associates, New York, NY.
E.E. Birch1,2, J. Wang1, S.R. Hatt3, A.R. O’Connor4, J.R. Drover5, J.M. Holmes3. 1Pediatric
Eye Research Lab, Retina Foundation of Southwest, Dallas, TX; 2Ophthalmology,
UT Southwestern Medical Center, Dallas, TX; 3Ophthalmology, Mayo Clinic,
Rochester, MN; 4Orthoptics, University of Liverpool, Liverpol, United Kingdom;
5
Psychology, Memorial University, St. Johns, NL, Canada.
Purpose: Stereopsis is exquisitely sensitive to many of the more subtle disturbances
of the vision process, including uncorrected refractive error and sensory/motor
fusion problems, making accurate measurements of stereoacuity is critical for both
research and clinical purposes. We have developed a novel customizable computerbased random-dot stereoacuity test that overcomes many shortcomings of current
clinical stereo testing, such as incomplete dissociation, memorization, and parallax.
Our test can be presented on a standard CRT with direct viewing, or minimized on
a back-projected screen using a high resolution DLP projector and relay optics. Here
we compare the repeatability and reliability of the MVA Computerized RDS test to
existing clinical stereo tests.
Methods: Pairs of random-dot bitmap images were created in MatLab and displayed
at 1600x1200 resolution at 5 meters. Image pairs were alternated at 80Hz and viewed
though LCD shutter glasses oscillating in phase at the same frequency, completely
dissociating the image pairs without residual monocular cues. Sets of RDS images
were generated at 18cpd in approximately 0.125 log second steps from 9.9 - 237.6
seconds, and designed so that multiple sets of targets could be displayed on a single
screen, reducing test time. Stereoacuity thresholds of six healthy presbyopic subjects
(mean age 48.6yo) with normal binocularity were measured with best correction using
our new MVA RDS test and compared to threshold measurements from currently
available computerized RDS and stereo ring tests using red/green anaglyphs (Innova
ProVideo). Six threshold measurements were taken on each test (3 measurements on
two separate days) for each subject.
Results: Across all subjects, the MVA RDS test provided lower threshold values
(mean=38.5”) and lower standard deviation (mean SD=9.13”) than the clinical RDS
(mean=44.0”; mean SD=21.1”, p=0.029) and stereo ring test (mean=68.6”; mean SD=23.0”,
p=0.039). In terms of mean standard deviations as ratios of mean thresholds, the
MVA RDS test provided lower ratios than the clinical RDS (p=0.007) and stereo ring
test (p=0.044).
Conclusions: The MVA computerized stereoacuity test is a repeatable, valid test that
can incorporate a broad range of customized targets and can be scaled for different
distances, including optical minimization for near testing.
CR: R. Robilotto, None; G. Zikos, None; A. Selenow, None; S. Slotnick, None.
Support: None
2887 - A72
Monovision: Consequences for Depth Perception From Fine and Coarse
Disparities
Purpose: Distance stereoacuity data may be useful in assessing strabismic patients who
have differences in the distance and near angle of deviation, including intermittent XT.
We developed the Distance Randot ® Stereotest as an easily administered quantitative
test for distance stereoacuity in children as young as four years of age. Using a
prototype, we previously reported extensive testability, validity, and normative data.
Here we report normative and validity data for the final, commercially available
version of the test.
Method: The Distance Randot ® is a Polaroid vectographic book, presenting 2 shapes
at each of 4 disparities: 400, 200, 100, and 60 arcsec viewed at 3m through polarizing
glasses. The smallest disparity level at which the child can identify both shapes
is recorded as stereoacuity. We administered the Distance Randot ® to 31 normal
volunteers (4-36 y) and 39 strabismic patients (4-73 y). The prototype distance
stereoacuity test was also administered. Test-retest data were collected for the final
version of the test.
Results: Normative Distance Randot ® scores were similar to those obtained with
the prototype; 96.8% of normal scores were ≤100 arcsec. Test-retests were identical in
71% and within one disparity level in 96.8%. Among strabismic patients, 79.5% had
abnormal Distance Randot ® scores; the few with normal scores had incomitant or
intermittent deviations. Nil stereoacuity was found in 22 patients and confirmed in
90.9% of retests; 17 had measureable stereoacuity, confirmed in 91.4% of retests. Patients
with constant ET or XT (n=16) were more likely to have nil stereoacuity than patients
who had intermittent ET or XT (n=15)(100% vs 20%; z=7.75, p<0.001). Overall, Distance
Randot ® scores were highly correlated with prototype scores (rs = 0.90, p<0.001).
Conclusion: The tight clustering and high test-retest reliability of normative data
results in little overlap with scores from patients who have significant binocular
sensory disorders. Data from strabismic patients suggest that the Distance Randot ®
Stereotest is a sensitive measure of binocular sensory status that may be useful in
monitoring progression and/or recovery.
CR: E.E. Birch, Stereo Optical Corporation, F; J. Wang, Stereo Optical Corporation, F;
S.R. Hatt, Stereo Optical Corporation, F; A.R. O’Connor, Stereo Optical Corporation,
F; J.R. Drover, Stereo Optical Corporation, F; J.M. Holmes, Stereo Optical Corporation,
F.
Support: EY05EY05236 (EEB) and EY015799 (JMH)
2888 - A73
Effect of Binocular versus Monocular Viewing on Golf Putting Accuracy
C.E. Smith1A, L.M. Wilcox1A, R.S. Allison1B, O. Karanovic1, F. Wilkinson1A. ADepartment
of Psychology, BDepartment of Computer Science and Engineering, 1Centre for
Vision Research, York University, Toronto, ON, Canada.
Purpose: Traditionally presbyopia is treated using corrective bifocal or multifocal
lenses. An alternative is to correct one eye for near and the other for distance with
a method known as “monovision”. It is known that differential interocular blur can
degrade stereoacuity, and recent studies have confirmed that monovision treatment
increases stereoacuity thresholds. However, stereoacuity tests do not assess disparity
sensitivity in the coarse range. Given the proven link between stereopsis and stability,
we have measured the short-term effects of induced monovision on stereopsis over
a broad range of fine (fused) and coarse (diplopic) disparities at both near and far
viewing distances.
Methods: Stimuli were presented dichoptically using a time-sequential polarized
stereoscopic display. During each trial a line was presented for 300 ms with either
crossed or uncrossed disparity above a zero disparity fixation cross. Participants
indicated the direction of the depth offset. In one session baseline performance
was assessed with optimal optical correction. In another, monovision was induced
by adding -1D and +1D lenses in front of the dominant and non-dominant eyes
respectively. We assessed performance at distances of 62 and 300 cm in counterbalanced
blocks. Within each block, the stimuli were presented at 5 fine disparities ranging
from 60 to 2400 arcsec and 5 coarse disparities ranging from 1o to 3.5o.
Results: Induced monovision resulted in decreased accuracy relative to baseline in the
fine disparity range, but effects were minimal in the coarse range. Monovision also
had a larger impact on performance at a viewing distance of 300 cm than at 62 cm.
Conclusions: Induced monovision not only increases stereoacuity thresholds, but
degrades depth discrimination across the range of fusable disparities in young
observers. This effect on fine disparity is accentuated at larger viewing distances
typical of fixation distances during walking, suggesting that stability during
locomotion may be degraded. However, we also found that coarse stereopsis was
relatively spared, and this may offset the observed losses.
CR: C.E. Smith, None; L.M. Wilcox, None; R.S. Allison, None; O. Karanovic,
None; F. Wilkinson, None.
Support: The Canadian Institute for Health Research and York University
R.C. Bulson, K.J. Ciuffreda, D.P. Ludlam. Department of Vision Sciences, SUNY
College of Optometry, New York, NY.
Purpose: To elucidate the role of binocular vision, including both stereopsis and
vergence innervation, in the complex task of golf putting.
Methods: The putting accuracy of sixteen, visually-normal inexperienced golfers
(range 23-66 years, mean=35 years) was assessed for small (3cm) and large (12cm)
targets located at 3, 6, and 9 feet with distance corrective lenses in place. All subjects
had normal binocular vision with stereopsis less than 40 sec arc, were free from any
ocular or neurological disease, and were visually asymptomatic. Subjects performed
the task under either normal binocular or monocular viewing conditions. All testing
was performed in a counterbalanced manner with respect to target size and viewing
condition.
Results: Putting accuracy (% successful putts) was significantly better under binocular
versus monocular viewing conditions, especially for the smaller target. For the smaller
target, putting accuracy was better under binocular versus monocular viewing
conditions for 10 out of 12 (83%, p=0.019), 11 out of 12 (92%, p=0.003), and 12 out of 12
(100%, p<0.001) of the subjects for the 3, 6, and 9 foot test distances, respectively. The
percentage improvement in putting accuracy under binocular viewing conditions
for the small (3cm) target was approximately 14%, 8%, and 13% for the 3, 6, and 9 foot
target distances, respectively. For the larger target, the trends were similar, but much
smaller in magnitude (0.5-7%).
Conclusions: These findings are consistent with earlier studies demonstrating
improved athletic performance under binocular versus monocular viewing conditions.
Binocular vision is an important factor in successful completion of a complex
sensorimotor task, such as golf putting. The additional depth-related cues provided
by stereopsis and vergence innervation appear to be crucial for more precise and
detailed tasks, such as demanded by the smaller target.
CR: R.C. Bulson, None; K.J. Ciuffreda, None; D.P. Ludlam, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
2885-2888
Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81
325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY
2889 - A74
Vergence Induced by Optic-Flow Motion in Patients With Strabismus
2890 - A75
Vergence and Three-Dimensional Perception Induced by Ground-Plane Motion
D. Yang, E.S. Hald, R.W. Hertle, Z. Tai. Ophthalmology, Univ of Pittsburgh
ChildrensHosp, Pittsburgh, PA.
Z. Tai, R.W. Hertle, E.S. Hald, D. Yang. Ophthalmology, University of Pittsburgh,
Pittsburgh, PA.
Purpose: Subjects with strabismus have shown deficits in disparity vergence eye
movements. We investigated how their damaged vergence system responded to optic
flow motion in the ground plane.
Methods: Backward/forward motion of a sinusoidal grating pattern which does not
have horizontal disparity was displayed on a computer monitor in the ground plane
and binocular movements were recorded with a video-based eye tracking system
(EyeLink 1000 desktop). Subjects looked at the center of the pattern for 5 seconds in
each trial and various velocities and two different directions were randomized. Openloop and closed-loop vergence velocities, amplitudes, and latencies were quantified
and compared with normal subjects.
Results: In normal subjects, involuntary horizontal vergence nystagmus was recorded.
In patients, robust vergence nystagmus was also induced. The slow-phase velocity
of open-loop vergence from strabimus subjects was higher than normal subjects and
the latency of the initail responses was shorter than normal subjects. The closed-loop
vergence from strabismus patients was as strong as normal subjects.
Conclusion: The vergence system in strabismic patients is responsive to optic flow
motion. The results suggest that optic flow motion may be independently processed in
a different pathway and optic flow vergence may become dominant in daily vergence
control in patients with binocular disparity processing damage.
CR: D. Yang, None; E.S. Hald, None; R.W. Hertle, None; Z. Tai, None.
Support: NIH grant EY015797, RPB and CMRF of University of Pittsburgh
Purpose: A moving observer experiences optic flow stimulus during fore/aft
movements. It is known that optic flow induced vergence eye movements to stabilize
gaze (Yang et al 1999). However, disparity stimuli are also available to the moving
observer in the real world and their effect on optic flow vergence is not clear. To study
the effect of disparity on vergence induced by optic flow motion in the gound plane,
we tested subjects with a modified grating pattern used to induce optic flow vegence
(Yang et al 2007 and Zhu et al 2008).
Methods: By interpolating sinusoidal grating stripes with reversed polarity on a
sinusoidal grating pattern, a checkboard-like pattern was generated. The motion of
the checkboard pattern or a sinusoidal grating pattern was displayed on a computer
monitor in the ground plane and binocular movements were recorded with a videobased eye tracking system (EyeLink 1000 desktop). Three normal subjects looked at
the center of the pattern for 8 seconds in each trial and they were instructed to press
a gamepad button when they perceived a 3 dimensional (3D)layer in the pattern.
All experimental conditions including various velocities, two patterns, and two
directions were randomized. Vergence amplitudes, velocities, and latencies were
quantitively analyzed.
Results: Horizontal vergence in a form of optokintic nystagmus was induced by
each pattern. In addition, a clear 3D layer was perceived by all 3 subjects when the
checkboard pattern was used. The 3D perception occured 1.5-5 seconds after the
initiation of the motion and it was usually associated with an brief increase in vergence.
The latency and velocity of the initial open-loop responses were the same for the two
different stimulus patterns. The velocity of closed-loop vergence was significantly
increased by 20-30% when checkboard pattern was used. There was no increase in
vergence with monocular viewing of checkboard pattern.
Conclusion: A 3D perception was induced by disparity from motion in the groundplane. Vergence induced by optic flow motion was enhanced by disparity from
motion. The results suggest that optic flow and disparity work together during fore/
aft motion to stabilize gaze.
CR: Z. Tai, None; R.W. Hertle, None; E.S. Hald, None; D. Yang, None.
Support: NIH EY015797,RPB,and CRMF of University of Pittsburgh
2891 - A76
Vergence Dynamics in Traumatic Brain Injury
2892 - A77
Accommodative Training to Reduce NITM and Improve Accommodative
Accuracy in Asymptomatic Myopic Young-Adults
D.G. Szymanowicz, P. Thiagarajan, W. Green, K.J. Ciuffreda, D. Ludlam. State College of
Optometry, State University of New York, New York, NY.
Purpose: Recent retrospective studies have found abnormalities of static clinical
vergence parameters in traumatic brain injury (TBI) patients. The purpose of the
present study was to investigate the first-order symmetric vergence dynamics in
TBI.
Methods: Non-strabismic TBI patients (n=10, mean age 30.2±5.01years) with near vision
symptoms, and asymptomatic visually-normal (non-TBI) subjects (n=10, mean age
25.2±0.91years), were tested. Binocular horizontal position of the eyes was recorded
objectively and continuously using the Power Refractor II, based on infra-red video
photorefraction, with a sampling rate of 12.5Hz and resolution of < =0.5 degrees. The
stimulus amplitude was 6.5º for both convergence and divergence. Targets comprised
the red fixation LED located on the measuring head of the power refractor at 1m
and a white LED placed at 0.3m, both aligned along the midline. Subjects altered
bifixation between the targets every 3-4 seconds upon command for one minute.
Three convergence and 3 divergence responses were obtained for analysis from the
eye position traces for each subject. An exponential decay function was fit to the traces,
and the response amplitudes and time constants of convergence and divergence were
obtained. The peak velocities were derived from first-order differentiation of the
exponential equation. The mean amplitude, time constant, and the peak velocity of
the responses of the TBI and normal groups were compared.
Results: Mean convergence response amplitude of the TBI group (6.4±0.3°) and the
normal group (6.2±0.2°) was not significantly different (p=0.65). Similarly, mean
divergence response amplitude of the TBI group (6.4±0.2°) and the normal group
(6.5±0.2°) was not significantly different (p=0.77). However, there were significantly
reduced (p<0.01) mean peak velocities and increased time constants for both
convergence (15.5±0.94°/sec; 432.4±31ms) and divergence (15.6±0.96°/sec; 448.8±39.5ms)
in the TBI group when compared to convergence (28.7±1.2°/sec; 221±9.6ms) and
divergence (24.8±1.2°/sec; 273.4±19.1ms) in the visually-normal group, respectively.
Conclusions: The TBI group demonstrated significantly slowed dynamic vergence
responses. Since the neural control for vergence involves numerous motor and premotor
areas, it appears that multiple axonal pathways are susceptible to diffuse axonal
injury from the TBI, resulting in slowed vergence responsivity. More specifically, we
speculate it may compromise the firing rate of vergence burst cells that are related to
vergence velocity. However, the similar response amplitudes in both groups suggest
unaffected activity of vergence tonic cells related to vergence angle.
CR: D.G. Szymanowicz, None; P. Thiagarajan, None; W. Green, None; K.J. Ciuffreda,
None; D. Ludlam, None.
Support: None
K.J. Ciuffreda, B. Vasudevan, D. Ludlam. Vision Sciences, SUNY College of
Optometry, New York, NY.
Purpose: To assess objectively changes in the NITM (nearwork-induced transient
myopia) parameters of initial magnitude and its decay duration, as well as accuracy
of the near accommodative steady-state response and clinically-based accommodative
facility, following 6 weeks of home-based monocular and binocular accommodative
vision training (i.e., oculomotor learning) in asymptomatic myopes.
Methods: 10 young-adult myopes with a mean age of 23.6 (±2.2) participated. The
experimental paradigm consisted of a baseline session and two follow-up sessions at
the end of the 3rd and 6th weeks of training. At the first session, baseline refractive
state and the selected static and dynamic accommodative functions were assessed
objectively. Measurements were repeated at the two follow-up sessions. Conventional
home-based vision training emphasizing dynamic aspects using step inputs included
lens flippers (±2D) at near (40cm), Hart chart at distance (6m) and near (40cm), and
prism flipper (6pd) training at near (40cm), all of which were performed for 20 minutes
a day 5 days a week for 6 weeks (10hrs total). Thus, both blur and vergence-driven
accommodation, and their interactions, were involved.
Results: The dynamic accommodative response functions improved significantly
with training, whereas the steady-state (static) response functions were only slightly
improved. Dynamic: NITM decay duration decreased significantly with training from
101secs to 74secs. Lens flipper rate increased significantly from 11 to 16cpm in the OD,
11 to 19cpm in the OS, and 8 to 11cpm in the OU. Hart chart rate increased significantly
from 22 to 33cpm in the OD. Static: Initial NITM magnitude decreased slightly from
0.53D to 0.47D, whereas the steady-state accommodative response increased slightly
from 2.64D to 2.72D, following training.
Conclusions: Training of the accommodative system resulted primarily in improved
dynamics in both the laboratory and clinical measures. The results suggest the presence
of rapid motor learning involving both the parasympathetic and sympathetic systems.
Faster dynamics would result in decreased time-integrated retinal defocus, a potential
myopigenic factor. In addition, the results suggest improved blur processing with
training.
CR: K.J. Ciuffreda, None; B. Vasudevan, None; D. Ludlam, None.
Support: COVD
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
2889-2892
Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81
325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY
2893 - A78
Nitm Following Marked Sustained Accommodation at Near
2894 - A79
The Effect of Induced Anisometropia on Accommodation and Vergence During
Development
M. Arunthavaraja, K.J. Ciuffreda, B. Vasudevan. State College of Optometry, State
University of New York, New York, NY.
T.R. Candy, S.R. Bharadwaj. Optometry, Indiana University, Bloomington, IN.
Purpose: It has been speculated that NITM (accommodatively-based nearworkinduced transient myopia) is myopigenic in nature. Thus, the purpose of the present
investigation was to determine objectively the initial magnitude of NITM, and its
potential additivity, following successive but interrupted periods of marked, sustained
accommodation at near in asymptomatic young adult myopic subjects.
Methods: Fifteen visually normal, asymptomatic young adults (ages 18 - 28 years) were
tested with full distance refractive correction. They included 9 early-onset (EOM) and
6 late-onset (LOM) myopic subjects. Accommodation was assessed objectively with
a Canon R-1, open-field infrared auto-refractor under monocular viewing conditions
(RE). The distance refractive state was measured immediately before and after each of
the 3 ten minute periods of focusing upon a moderate contrast (50%), near target (12
cm; 8D) subtending 6 degrees. The task was repeated twice with a 5-minute inter-task
rest period of imposed far viewing. NITM was defined as the post-task minus pre-task
change in distance refractive state immediately following each task.
Results: Significant amounts of NITM were generated following each trial. These
ranged from 0.11 to 0.71D, with a mean of 0.31D. The group mean NITM was 0.32,
0.29, and 0.31D for trials 1, 2, and 3, respectively. For the EOMs subgroup, NITM was
0.28, 0.30, and 0.34D, while for the LOMs subgroup, it was 0.38, 0.29, and 0.26D, for for
trials 1, 2, and 3, respectively. However, additivity of NITM was not found following
the sequence of interrupted near tasks.
Conclusions: There was no evidence of NITM additivity following a marked and
sustained, but interrupted, near task. Although NITM has been reported to be additive
following long periods of sustained reading (Vasudevan & Ciuffreda, 2008), providing
rest periods between near task trials appears to prevent a cumulative effect. These
findings support the idea of far viewing being protective in nature from myopia
development.
CR: M. Arunthavaraja, None; K.J. Ciuffreda, None; B. Vasudevan, None.
Support: None
Purpose: Anisometropia is associated with abnormal visual development but does not
result in routine presentation for an eye examination as it has no obvious signs and
symptoms. Little is known about its influence on visual function during infancy and
the pre-school years. Here, we optically induce anisometropia in typically developing
infants and children for brief periods of time to determine the effect on accommodation
and vergence - two functions that help maintain clear and single vision.
Methods: Accommodative and vergence responses were recorded simultaneously
using a PowerRefractor (25Hz). Twenty subjects (3.7 months to 29.8 years) watched
a high contrast cartoon movie (1/f amplitude spectrum) on an LCD screen that
moved between 80cms (1.25D) and 33cms (3.0D) at 0.50D/s, with a stable period
of 4s at each viewing distance. This protocol was performed under four viewing
conditions: i) habitual binocular viewing, ii and iii) with a +2D or +4D lens over
one eye (induced anisometropia conditions) and iv) with one eye occluded using an
IR filter. Accommodative and vergence gains were calculated for the 1.75D or MA
stimulus for each viewing condition.
Results: Binocular accommodative gains (Mean +/- SEM: 0.99 +/- 0.08) were significantly
different (p=0.001) from monocular accommodative gains (0.47 +/- 0.09) for all ages
(main effect: p=0.55). Accommodative gains with 2D (0.77 +/- 0.08) and 4D (0.76 +/- 0.08)
of induced anisometropia were not significantly different from each other (p=0.99) or
the binocular (p= 0.27 & 0.26, respectively) and monocular (p=0.07 & 0.06, respectively)
conditions. The vergence gains were also significantly different for binocular (0.91
+/- 0.04) and monocular conditions (0.30 +/- 0.05) (p<0.001). The vergence gains with
2D (0.85 +/- 0.04) and 4D (0.69 +/- 0.04) of anisometropia fell between the two values.
Both were significantly different from monocular conditions (p<0.001), but only the
4D was significantly different from binocular conditions (p=0.01). Subject’s age only
had a marginal effect on the vergence gain (main effect: p=0.04).
Conclusion: Accommodative and vergence performance of the typically developing
visual system deteriorates in the presence of transiently induced anisometropia.
However, some binocular cues appear to remain with induced anisometropia of 2D
and 4D, as indicated by the accommodative and vergence gains being somewhat
higher than in monocular viewing. These results are consistent with the reduction
in available disparity information for vergence and poorer retinal image quality for
controlling accommodation.
CR: T.R. Candy, None; S.R. Bharadwaj, None.
Support: NIH Grant EY 014460 (TRC) Fight for Sight post-doctoral fellowship (SRB)
2895 - A80
Accommodative-Vergence and Vergence-Accommodation Cross-link Gains in
Preschoolers
2896 - A81
Visuo-attentional Abilities in Healthy Children Compared to Children with
Ophthalmologic Disorders
D.F. Teel, S.R. Bharadwaj, T.R. Candy. Indiana University, Bloomington, IN.
M. Vilayphonh1,2, C. Cavézian1, L. Laloum 3, L. Watier4, M. De Agostini4, S. Chokron1.
1
Laboratoire de Psychologie et de Neurocognition, CNRS, UMR 5105, Genoble,
France; 2Service de neurologie, Fondation Ophtalmologique Rothschild, Paris,
France; 3Service de médecine interne, Hôpital des Quinze-Vingts, Paris, France;
4
U780 ifr 69, INSERM, Villejuif, France.
Purpose: Accommodation and vergence interact through neural cross-links such
that accommodation can drive vergence (AC/A ratio) and vergence can drive
accommodation (CA/C ratio) to provide clear and single vision. Inappropriate crosslink gains are believed to lead to binocular vision anomalies. While the two systems
interact from early infancy, adult-like interactions between them may be inappropriate
during development. Relative to adults, reduced head size and typically hyperopic
refractive error result in reduced vergence demands and elevated accommodative
demands during infancy and early childhood. This study aims to make the first
within-subject measures of the gains of both response AC/A and response CA/C ratios
in a group of 2-4 year olds to understand strategies used to overcome these dissimilar
demands; an age at which accommodative esotropia commonly appears.
Methods: Accommodation and vergence responses were measured in a group of 2-4
year olds (mean age=3.3 ± 0.5 years) and a group of adults (mean age=28.1 ± 5.4 years)
using the PowerRefractor (25Hz). To measure the AC/A gain (MA/D), subjects watched
a high contrast cartoon movie (1/f amplitude spectrum) monocularly (open-loop
disparity driven vergence) while accommodation was stimulated using a -2D lens. To
measure the CA/C gain (D/MA), subjects watched a blurred version of the same movie
(filtered using a <0.2 cpd difference-of-gaussian) binocularly (open-loop blur driven
accommodation) while their vergence was stimulated using a 2MA prism.
Results: Response AC/A ratios were significantly higher (p=0.01) in adults (Mean +
SD: 0.90 ± 0.15 MA/D) than in children (0.58 ± 0.21 MA/D) while the response CA/C
ratios of adults (0.36 ± 0.2 D/MA) and preschoolers (0.45 ± 0.15 D/MA) were not
significantly different (p=0.335).
Conclusions: The response AC/A ratio (in MA/D) would be higher in 2-4 year olds
than in adults if the angular rotation of the eyes generated by the accommodativevergence cross-link remained constant with age. Conversely, the response CA/C ratio
(in D/MA) would be lower than in adults if the dioptric change in focus generated by
the vergence-accommodation cross-link remained constant with age. These results
do not follow these predictions, indicating a recalibration of both cross-link gains
with age.
CR: D.F. Teel, None; S.R. Bharadwaj, None; T.R. Candy, None.
Support: NEI Grant EY014460(TRC) NEI K12 Grant EY15504(DFWT)
Purpose: Previous studies suggest that peripheral visual alteration could modify
visual cognition. One can assume that an early decrease in visual acuity (i.e., related
to peripheral damage in childhood) could lead to visuospatial cognitive disorders.
Moreover, it has been shown that these cognitive impairments could underlie specific
learning disabilities such as difficulties in written language. The goal of the current
study was to explore visuo-attentional skills (e.g., visual scanning strategies, visual
memory and visual processing) in children with ophthalmologic disorders.
Methods: 106 right-handed children (28 patients; 78 healthy controls), aged from 4
to 8, with normal or corrected-to-normal vision, performed six visuospatial tasks,
including three cancellation tasks (Teddy Bear, Bell, and the Corkum tests), visuospatial
working memory tasks (Borel-Maisonny symbol orientation task, shape and letter
matching tasks), and a visual discrimination task (the Embedded Figures Test). The
patients were diagnosed with either a simple strabismus or a strabismus associated
with another ophthalmologic disorder.
Results: Healthy controls performed better than patients in the Teddy bear, Triangle,
T2 Corkum cancellation task, Embedded Figures Test. Age played an important role
for the Triangle, T2 Corkum, Embedded Figures Test, and symbol orientation tasks
where the oldest group showed better results than the youngest children.
Conclusions: This study gives information regarding visuo-attentional development
in a large sample of healthy children. Our results highlight that visuo-attentional
abilities are not optimal at 4 years old but indeed improve at least until 8 years. Yet,
in ophthalmologic children, despite having corrected-to-normal vision, a long-lasting
impaired visuo-attentional skill is observed. These findings suggest that attention
and spatial skills training could be proposed in young children with corrected vision
before formal reading education.
CR: M. Vilayphonh, None; C. Cavézian, None; L. Laloum, None; L. Watier, None; M.
De Agostini, None; S. Chokron, None.
Support: B and E Rothschild Fondation
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
2893-2896
Tuesday, May 5, 1:45 PM - 3:30 PM Palm A Paper Session Program Number Range: 3037 - 3043
343. Extraocular Muscles and Nystagmus Organizing Section: EY
3037 - 1:45PM
Retinoic Acid Regulates Orbital Development and Extraocular Muscle
Organization in Zebrafish
3038 - 2:00PM
Nerve-Muscle Interplay in the EOMs: Effects of Progressive Denervation on
Human and Transgenic Mice With Amyotrophic Lateral Sclerosis (ALS)
A. Kahana1, F. Elsaeidi1, D. Demiri1, B.L. Bohnsack1, A.-A. Calinescu1, D. Goldman2.
1
Kellogg Eye Center, Univ of Michigan, Ann Arbor, MI; 2Biochemistry, Molecular
and Behavioral Neuroscience Institute, Univ of Michigan, Ann Arbor, MI.
F. Pedrosa Domellof 1A, T. Brännström1B, P. Andersen1C, S. Marklund1D, J.-X. Liu1E.
A
Clinical Sciences/Ophthalmology, BMedical Biosciences, Division of Pathology,
C
Clinical Neurosciences, DMedical Biosciences, Division of Clinical Chemistry,
E
Integrative Medical Biology, Anatomy, 1Umea University, Umea, Sweden.
Purpose: Orbital disease can involve reactivation of embryogenic pathways. We aim to
utilize a novel zebrafish model of orbital development to evaluate the role of the neural
crest in orbital organization.
Methods: Zebrafish transgenic strains were used for real-time fluorescence and confocal
microscopy to assess orbital development following experimental perturbations to the
retinoic acid signaling system, including inhibition of RA synthesis with DEAB. In situ
hybridization and immunohistochemistry experiments were used to complement the
live microscopy experiments and identify potential targets.
Results: Retinoic acid (RA) is a key morphogen during embryogenesis and a powerful
teratogen, and its synthesis is tightly regulated both spatially and temporally. RA is also
a key regulator of neural crest development. Evidence from mouse molecular genetics
revealed a key role for RA signaling in the regulation of orbital development, although the
exact mechanism and key intercellular interactions remain to be discovered. We developed
a zebrafish model for studying orbital development utilizing transgenic strains for realtime assessment of extraocular muscles (EOM) and cranial neural crest development,
along with ISH and IHC experiments. Using this model, we inhibit retinoic acid synthesis
with DEAB beginning at 24hpf and show that EOM differentiate appropriate, but the
exact anatomic localization of EOMs around the eye is disrupted (figure).
Conclusions: Zebrafish orbital development
reveals a dependence on RA signaling that is
very similar to data from existing mammalian
models. The zebrafish model allows us to
further characterize the key cellular
interactions and signaling pathways using live
microscopy techniques where cellular
microenvironments around the eye can be
observed intact. This is a powerful model that
has great promise to further our understanding
of orbital and extraocular muscle development
and disease.
CR: A. Kahana, None; F. Elsaeidi, None; D. Demiri, None; B.L. Bohnsack, None; A.-A.
Calinescu, None; D. Goldman, None.
Support: NIH Grants K08EY018689 to AK; 5R01EY018132 to DG; 5P30EY007003 to the
Kellogg Eye Center; and 5P30CA46592 to the University of Michigan’s Cancer Center.
3039 - 2:15PM
The Effect of Recession Surgery on Rabbit Extraocular Muscle Myosin
Expression and Satellite Cell Activity
R.S. Antunes-Foschini1, B. Limmer2A, S.P. Christiansen2A, L.K. McLoon2B.
1
Ophthalmology, HC- FMRP - University of Sao Paulo, Ribeirao Preto, Brazil;
A
Ophthalmology and Pediatrics, BOphthalmology and Neuroscience, 2University of
Minnesota, Minneapolis, MN.
Purpose: Surgical recession of extraocular muscles (EOM) is a common treatment
for strabismus and other motility disorders. Recession involves the removal of the
muscle from its scleral insertion and reattaching the muscle at a point posterior to the
original site of insertion. The purpose is to reduce the force of an overacting muscle
and restore normal eye position. We examined the effect of this procedure on the
activity of satellite cells and myosin heavy chain isoform expression in the recessed
extraocular muscle of adult rabbits compared to normal control muscles.
Methods: The insertion of the superior rectus (SR) muscle was detached from the
sclera and sutured 7 mm posterior to its original insertion site. After 7 days the animals
were injected every 2 hours for 12 hours with bromodeoxyuridine (brdU), followed
by a 24 hour brdU-free period. The superior rectus muscles were examined for brdU
incorporation and neonatal and developmental myosin heavy chain (MyHC) isoform
expression changes in the mid-region and tendon ends of the muscles and compared
to control superior rectus muscles.
Results: In the recessed muscle, the percentage of brdU positive satellite cells in the
orbital layers was increased compared to normal control SR muscles, and particularly
elevated in the tendon region of the treated muscle. The global layer showed little
alteration in satellite cell rates of division, with only a small increase in the tendon
end of the global layer. In the global layer of both the middle and tendon ends of the
recessed muscles, neonatal and developmental MyHC expression was significantly
decreased.
Conclusions: Surgical recession of the superior rectus muscle resulted in an increase
in satellite cell division at 7 days post-surgery. In contrast to surgical resection,
recession surgery resulted in a marked decrease in expression of the immature
myosin heavy chain isoforms. This demonstrates that the muscles respond to the
reduction in length by remodeling both their myosins and satellite cell activity. It may
be possible to improve the post-surgical effects of recession surgery by modulating
these processes.
CR: R.S. Antunes-Foschini, None; B. Limmer, None; S.P. Christiansen, None; L.K.
McLoon, None.
Support: Fapesp 2007/05260-0, NIH EY15313 and EY11375
Purpose: To explore extent and consequences of progressive denervation in the EOMs
of ALS patients and of transgenic ALS mouse models.
Methods: EOM samples obtained at autopsy from 7 ALS patients and from 4 elderly
controls (72-86 y), 7 adult controls (26-56 y), as well as from transgenic mice with
SOD1 mutations (D90A, G93A, G85R) paralleling familiar ALS, were processed for
immunocytochemistry with antibodies against Schwann cell markers (S-100, p75,
GFAP), gangliosides GD1b and GQ1b/GT1a, parvalbulmin, myosin heavy chains
and laminin chains. Neuromuscular junctions (NMJs) were identified with alphabungarotoxin and acetylcholinesterase.
Results: Differences in the expression of gangliosides GD1b and GQ1b/GT1a and
Schwann cell marker S-100 at the NMJs and nerves were noted in the human EOMs
of ALS patients compared to those of the elderly controls. Parvalbumin was absent
or scarce in EOM nerve trunks of ALS patients, with few exceptions. Changes in the
composition of the extracellular matrix observed in EOMs of human familial ALS with
D90A mutation were also present in the corresponding transgenic mouse. Further
characterization of the EOMs in the transgenic mice is ongoing.
Conclusions: There are signs of denervation of the human EOMs in late stages of ALS
although these muscles appear selectively spared at the muscle fiber level. The presence
of high levels of parvalbumin have been proposed to be protective for oculomotor
neurons in ALS but in advanced stages of the disease this difference in calcium-binding
proteins is no longer apparent in most cases. The identification of similar endpoints
in the EOMs of patients with D90A mutation and the ALS transgenic mice carrying
the same mutation indicates that this is a useful model to study the temporal aspects
of progressive denervation in the EOMs and to explore aspects of muscle-nerve
interplay that protect the EOMs in motoneuron disease. Finally knowledge on the
effects of denervation may give us insights on the spatial organisation of motor units
and fascicle organisation in the EOMs.
CR: F. Pedrosa Domellof, None; T. Brännström, None; P. Andersen, None; S.
Marklund, None; J.-X. Liu, None.
Support: Swedish Research Council (63x-20399), Synfrämjandets Forskningsfond,
Stiftelsen Kronprinsessan Margaretas Arbetsnämnd för Synskadade KMA
3040 - 2:30PM
A Comparison of Clinical and Eye Movement Characteristics Between Albinism
and Idiopathic Infantile Nystagmus With and Without Mutations in the FRMD7
Gene
A.A. Kumar, F.A. Proudlock, S. Thomas, I. Gottlob. Ophthalmology, University of
Leicester, Leicester, United Kingdom.
Purpose: No differences between nystagmus associated with albinism and idiopathic
infantile nystagmus (IIN) have been described. Recently mutations in a novel gene
called FRMD7 have been found which allow definitive identification of a homogenous
group of idiopathic nystagmus patients. We have compared clinical and eye movement
characteristics between albinism and IIN with and without mutations in the FMRD7
gene
Methods: Visual acuities and eye movements (infrared pupil tracker) were recorded
from 50 albino subjects, 83 subjects with the FRMD7 mutation and 45 subjects without
the FRMD7 mutation
Results: Mean visual was significantly worse in albinos compared to IIN patients
(p<<0.0001). Although there was no significant differences between the groups
(p>0.05) for nystagmus amplitude, the frequency of nystagmus was significantly
slower in albinism (p<<0.0001). In addition, nystagmus associated with albinism
was significantly more likely to be jerk nystagmus rather than pendular nystagmus
compared to FRMD7 group (p<<0.0001). The most common waveform associated
with albinism was pure jerk nystagmus, whereas non-FRMD7 was more likely to be
associated with jerk with extended foveation
Conclusions: Contrary to available literature, nystagmus associated with albinism
shows distinct differences to IIN both with and without FRMD7 mutations. This
suggests the possibility of different underlying mechanisms to albinism and IIN in
generating eye oscillations although these are yet to be elucidated
CR: A.A. Kumar, None; F.A. Proudlock, None; S. Thomas, None; I. Gottlob,
None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
3037-3040
Tuesday, May 5, 1:45 PM - 3:30 PM Palm A Paper Session Program Number Range: 3037 - 3043
343. Extraocular Muscles and Nystagmus Organizing Section: EY
3041 - 2:45PM
Foveation and Acuity Deficits in Patients With Idiopathic Infantile Nystagmus
Syndrome Across a Wide Age Range
3042 - 3:00PM
Spectral Domain Optical Coherence Tomography in the Oculocutaneous Albino
Population
J. Felius1,2, D.R. Stager, Sr. 2, C.H. Vu1. 1Retina Foundation of the Southwest, Dallas,
TX; 2Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX.
T.H. Cronin1, R.W. Hertle1, H. Ishikawa1,2, J.S. Schuman1,2. 1UPMC Eye Center, Eye and
Ear Institute, University of Pittsburgh School of Medicine, Ophthalmology and
Visual Science Research Center, Department of Ophthalmology, Pittsburgh, PA;
2
Department of Bioengineering, Swanson School of Engineering, University of
Pittsburgh, Pittsburgh, PA.
Purpose: Previously we introduced the Nystagmus Optimal Foveation Function
(NOFF) (Felius et al, 2008 ARVO) as an objective ocular motor outcome measure for
infants and young children in whom determining the Expanded Nystagmus Acuity
Function (NAFX) may not be feasible. The NAFX (Dell’Osso et al, 2002 Doc Ophthalmol)
is an established measure of foveation, predictive of visual acuity in patients with
idiopathic infantile nystagmus syndrome (IINS). Both NAFX and NOFF are based
on simultaneous position and velocity criteria that define ‘foveation’, but the NOFF
allows for within-session positional changes. Here we validate the NOFF against the
NAFX in older patients and study the relationship with visual acuity in IINS from
infancy to adulthood.
Methods: Calibrated horizontal eye movement data from 20 patients with IINS (age
6-27 years) were analyzed using both NOFF and NAFX algorithms, and the results
compared to binocular visual acuity from the same visit. The NOFF and age-corrected
visual acuity data were combined with data from 32 infants and young children (age
5 months-6 years) with IINS.
Results: In the 6-27 year age group, the NOFF (mean±SD=-1.5±1.7 logits) correlated
with the NAFX (0.43±0.24 logMAR) (r2=0.94; P<0.001). The acuity values predicted
by the NAFX algorithm correlated with measured visual acuity (0.36±0.25 logMAR)
(r2=0.37; P=0.004). For the combined group of 52 patients, age-corrected visual acuity
was associated with the NOFF and fit by a exponential model as previously described,
explaining 35% of the variance (P<0.001).
Conclusions: The excellent correlation with the NAFX in older children and adults
validates the NOFF as a measure of foveation. The strong relationship between
NOFF and visual acuity in IINS explained a similar amount of variance as in the
relationship between NAFX and visual acuity in older patients. These results confirm
the association between foveation statistics and binocular visual acuity in IINS and
extend it to a very young age range. The finding that only 1/3 of the variance in visual
acuity is explained by either NOFF or NAFX may be due to noise, the somewhat
limited range of this cohort, and/or it may indicate that factors other than foveation
statistics play a role.
CR: J. Felius, None; D.R. Stager, Sr., None; C.H. Vu, None.
Support: Vision of Children Foundation
Purpose: To evaluate the clinical utility of spectral domain optical coherence tomography (SDOCT) on macular imaging in eyes with oculocutaneous albinism (OCA) and to investigate the
afferent and efferent system in this unique subset of nystagmus patients using SD-OCT.
Methods: Three-dimensional macular cube scans (200x200x1024 samplings in a 6x6 mm
region centered on fovea) were obtained 3 times on each eye of 9 OCA patients. The central
macular thickness and horizontal eye movement frequency were recorded. The average
horizontal eye movement frequency was compared to that obtained from eye movement
recordings.
Results: The age range of the 9 patients was 7-58 years (average 18 years). All patients had
infantile nystagmus syndrome (INS) with 6 patients (67%) displaying aperiodicity. Macular
images were successfully obtained in 8 patients (89%). Seven patients (88%) demonstrated
“fovea plana” and one patient demonstrated a slight foveal depression. In agreement with
prior studies, central macular thickness was found to be increased in the OCA population
(284µm ± 56µm) compared to the general population. Eye movement frequency on SD-OCT
(range 2-4 Hz, average 3.5 ± 0.8 Hz) was calculated and agreed with that of eye movement
recordings (range 2-5 Hz, average 3.6 ± 0.6 Hz, paired student t-test, 95% CI [-0.7,0.5], p =
0.78).
Conclusions: SD-OCT provides detailed structural imaging of the sensory system of OCA
despite perpetual eye movement during scanning, revealing a major structural anomaly
in the macula. In addition, SD-OCT offers an alternative method of studying the motor
physiology of ocular oscillation in OCA.
Figure 1. Frame from SD-OCT movie demonstrating
fovea plana in oculocutaneous albino eye with
infantile nystagmus syndrome at 3-5 Hz
frequency.
Figure 2. SD-OCT image of y-plane demonstrating
horizontal nystagmus eye movements at 3-5 Hz
frequency.
CR: T.H. Cronin, None; R.W. Hertle, None; H.
Ishikawa, Bioptigen, P; J.S. Schuman, Carl Zeiss
Meditec, P; Bioptigen, P; Alcon, R; Allergan, R; Carl Zeiss Meditec, R; Heidelberg Engineering,
R; Merck, R; Lumenis, R; Optovue, R; Pfizer, R.
Support: NIH R01-EY013178-9, P30-EY008098; Eye and Ear Foundation (Pittsburgh, PA);
Research to Prevent Blindness
3043 - 3:15PM
Neural Circuit involved in Idiopathic Nystagmus Syndrome Based on fMRI
L.E. Leguire, IV1A,2A, N.H. Kashou1B, N. Fogt2B, M. Smith1B, J.R. Lewis2A,2C, R. Kulwin1B,
G. Rogers1A,2A. AOphthalmology, BRadiology, 1Nationwide Children’s Hospital,
Columbus, OH; AOphthalmology, BCollege of Optometry, CBiomedical Engineering,
2
Ohio State University, Columbus, OH.
Purpose: Idiopathic Nystagmus Syndrome (INS) is characterized by early onset
alternating series of slow and rapid eye movements which can manifest in different
waveforms and genetic lines. The neural circuitry of INS is not known.
Methods: A novel fMRI method was utilized to identify the neural circuitry for INS
in humans by use of a GE 3T MRI scanner utilizing FEAT-FSL and FILM time series
analysis with a cluster significance threshold of P=.01. The null point, a gaze position
with minimal nystagmus, was utilized as the “off” condition and a gaze position
with robust nystagmus was utilized as the “on” condition. Standard on-off fMRI
sequence was employed whereby a fixation point alternated between the null and
robust nystagmus positions. Eye movements were recorded with an fMRI compatible
eye tracker (ASL) and observed in real time to ensure subject compliance and to
quantify oculomotor function in “on” and “off” states. INS subjects (N= 4) included
three family members (mother and two daughters) with autosomal dominant INS as
well as age and gender matched normal controls (N=3).
Results: Three of four INS subjects demonstrated significant increased activation of
the Declive of the Cerebellum while no normal subjects, under identical conditions,
showed activation of the Declive. Both groups showed significant activation in the
occipital lobe (Brodmann Areas 17, 18, 19, Cuneus).
Conclusions: A novel fMRI method demonstrated that the Declive of the Cerebellum
is actively involved in INS. These are the first results to identify the Cerebellum, and
specifically the Declive, as a possible site for the oculomotor dysfunction associated
with INS.
CR: L.E. Leguire, IV, None; N.H. Kashou, None; N. Fogt, None; M. Smith, None; J.R.
Lewis, None; R. Kulwin, None; G. Rogers, None.
Support: Ohio LIONS Eye Research Foundation, Fight for Sight, Inc (GA03023)
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
3041-3043
Tuesday, May 5, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 3189 - 3200 / D718 - D729
356. Optic Nerve Injury and Regeneration Organizing Section: EY Contributing Section: RE
3189 - D718
In Vitro Characterization of Novel Neuroprotective Phosphine-Borane
Complexes
3190 - D719
Identification of Protein Targets of Novel Neuroprotective Sulfhydryl Reducing
Drugs
N.J. Niemuth1, C.J. Lieven1, L.A. Levin1,2. 1Ophthalmology and Visual Sciences,
University of Wisconsin, Madison, WI; 2Ophthalmology, University of Montreal,
Montreal, QC, Canada.
A.L. Kloosterboer1, J.R. Ribich1, L.A. Levin1,2. 1Ophthalmology and Visual Sciences,
University of Wisconsin Medical School, Madison, WI; 2Ophthalmology, University
of Montreal, Montreal, QC, Canada.
Purpose: Phosphine-borane (PB) complexes bis (3-propionic acid methyl ester)
phenylphosphine borane complex (PB1) and (3-propionic acid methyl ester)
diphenylphosphine borane complex (PB2) are novel neuroprotective compounds.
We previously demonstrated that they have a positive, dose-dependent effect on the
viability of RGCs after axonal injury (Schlieve et al., Exp Eye Res 83:1252, 2006), which
we hypothesize results from their ability to chemically reduce critical disulfides
formed as a result of oxidation by reactive oxygen species. We performed in vitro
testing of the effectiveness of these complexes and their utility as drugs, focusing on
their reducing power, solubility, blood-brain barrier permeability, and accelerated
stability.
Methods: Relative reducing power was tested using Ellman’s reagent (DTNB), which
turns yellow when its disulfide linkage is reduced. Reaction of various concentrations
of dithiothreitol, tris (carboxyethyl) phosphine, PB1, or PB2 with 30 mM DTNB in
methanol was carried out in buffer at pH 5, 7, and 9. Octanol/water partitioning
was carried out on PB1 and PB2 to determine their solubility in aqueous solution. A
modified PAMPA assay was used to determine blood-brain barrier permeability of PB1.
An artificial membrane was created on a filter plate using porcine polar brain lipids
dissolved in hexanes. PB1 in PBS was placed in the donor well above the membrane,
and PBS placed in the acceptor well below the membrane. Concentration of PB1 in
each well after 18 hours was calculated by comparison to a standard curve of PB1 in
PBS. Accelerated stability was determined by incubating 4 mg of pure PB1 and PB2
in sand baths at 40°C and 60°C for 37 days, followed by HPLC.
Results: There was a linear relation between concentration and reducing power for
each compound. PB1 and PB2 had maximal reducing capability at pH 7. log Poct/wat
for PB1 was 0.65 (somewhat soluble) and for PB2 was 1.1 (minimally soluble). log Pe
for PB1 was -5.86 (Pe = 1.38x10 -6), a low BBB permeability similar to that of caffeine
and aldosterone. Peak areas for PB1 at 40°C and 60°C were 80% and 72% of control
respectively at 37 days. PB2 peak areas were 100% of control for both conditions at
37 days.
Conclusions: Both PB complexes are effective reducers of disulfides. PB2, while highly
lipophilic, is more stable than its water-soluble counterpart.
CR: N.J. Niemuth, None; C.J. Lieven, None; L.A. Levin, Assigned to Wisconsin
Alumni Research Foundation, P.
Support: NIH R21EY017970, P30EY016665 and an unrestricted departmental grant
from Research to Prevent Blindness, Inc.
Purpose: Previous work in our laboratory has shown elevated intracellular superoxide
is a critical event in the death of retinal ganglion cells (RGCs) after axotomy. The
sulfhydryl-reducing compounds tris(2-carboxyethyl) phosphine (TCEP) and bis(3propionic acid methyl ester) phenylphosphine borane complex (PB1) rescue RGCs
from apoptosis. We used a novel two-dimensional gel electophoresis method to
detect changes in oxidation state of protein sulfyhydryls after treatment with PB1 in
a transformed retinal ganglion cell-like cell line (RGC-5).
Methods: Cultured RGC-5 cells were treated with 10 μM PB1 for 8 hours following
which cellular and mitochondrial proteins were separated on a 4-20% polyacrylamide
gradient gel. The lane was excised, reduced with 25 mM dithiothreitol, rinsed, and
alkylated with 100 mM iodoacetamide. The excised slice was placed horizontally on
a second gel, electrophoresed into the second dimension, and stained with Pierce®
color silver stain or Sypro® Ruby.
Results: Several proteins were found in consistent locations below the diagonal
when prepared from control cells, but not cells treated with PB1, indicating that they
contained disulfides that were reduced by PB1.
Conclusions: A relatively small number of cellular and mitochondrial proteins are
targets for the novel reducing agent PB1, and one or more may be critical for its activity
as a neuroprotective agent.
CR: A.L. Kloosterboer, None; J.R. Ribich, None; L.A. Levin, Wisconsin Alumni
Research Foundation, P.
Support: NIH R21EY017970 and P30EY016665 and an unrestricted departmental grant
from Research to Prevent Blindness, Inc.
3191 - D720
Neurotrophic Effect of a Novel TrkB Agonist on Retinal Ganglion Cells
3192 - D721
Sequence of Apoptosis Signaling Induced by Serum Deprivation in
Differentiated RGC-5 Cells
Y. Hu1, S. Cho2, J.L. Goldberg1. 1Bascom Palmer Eye Institute, University of Miami
Miller School of Med, Miami, FL; 2Neuroscience Discovery Research, Wyeth
Research, Princeton, NJ.
Purpose: Retinal ganglion cells (RGCs) die in glaucoma and a number of other optic
neuropathies. Recently, novel TrkB monoclonal antibodies have been shown to be
able to activate TrkB receptors and exert neuroprotective and neurotrophic effects
(Qian et al., 2006). In previous study, we examined the ability of one of these, 29D7,
on RGC survival in culture. In the present study, we examined the ability of 29D7 on
RGC survival and neurite growth both in culture and in vivo.
Methods: RGCs from postnatal day (P)3-4 Sprague-Dawley rats were isolated to over
99% homogeneity by sequential immunopanning using a monoclonal antibody to
Thy1. RGCs were cultured in 96 well plates pre-coated with poly-D-lysine and laminin
at a density of 2x103 cells/well, in serum-free defined medium. RGC viability was
assessed after 1-3 days by an MTT assay. The activation of TrkB downstream signals
was confirmed by immunofluorescence and Western blot. Intravitreal injections of
29D7 were performed after ON axotomy, RGC survival was quantified using ß-III
tubulin immunostaining. Regeneration was assessed using retrograde flurogold (FG)
tracing in ON-peripheral nerve (PN) graft model.
Results: Similar to brain-derived neurotrophic factor (BDNF), the 29D7 antibody
strongly promoted RGC survival and neurite growth in vitro compared with medium
alone or control IgG at 24 hours in culture. Forskolin, which weakly supported RGC
survival on its own, potentiated the effect of 29D7. Intravitreal injection of 29D7
enhanced RGC survival but not regeneration in vivo 2 weeks after injury.
Conclusion: These findings demonstrate the potential for antibody-mediated TrkB
agonism as a potential therapeutic reagent to enhance RGC survival after injury or
in degenerative disease. Further studies are needed to elucidate the mechanistic
differences between TrkB agonist and BDNF.
CR: Y. Hu, None; S. Cho, Wyeth conflict of interest, I; J.L. Goldberg, None.
Support: NEI R21 EY017971 (JLG), The Glaucoma Foundation (JLG), NEI P30 EY014801
(UM), and an unrestricted grant from Research to Prevent Blindness
C.J. Lieven1, K.M. Thurber1, E.J. Levin1, L.A. Levin1,2. 1Ophthalmology and Visual
Sciences, University of Wisconsin Medical School, Madison, WI; 2Ophthalmology,
University of Montreal, Montreal, QC.
Purpose: Serum deprivation induces apoptosis in many cell types, but can be prevented
by drugs that scavenge or inactivate reactive oxygen species, implicating the latter
in apoptosis signaling. Previous work in our laboratory showed that superoxide was
an intracellular signal for cell death in primary retinal ganglion cells after axotomy,
a condition causing both axonal injury and deprivation of tectum-derived growth
factors. We studied superoxide signaling of serum deprivation-induced apoptosis in
a transformed retinal ganglion cell line (RGC-5), in order to elucidate whether it was
acting as an upstream or downstream signal.
Methods: We correlated superoxide levels with the time course of cytochrome c release
after serum deprivation. RGC-5 cells were cultured for 24 hrs and differentiated to a
neuronal phenotype with staurosporine. Four hours after differentiation, cells were
either left undisturbed, switched to a serum-free medium, or treated with etoposide,
a known inducer of apoptosis. Untreated and etoposide-treated cells were stained
with hydroethidium and fixed after 1 and 24 hours in culture. Serum-deprived and
untreated cells were similarly stained and fixed at 24 and 72 hrs post-treatment.
Cytochrome c was localized by immunofluorescence. Cells were photographed for
quantitative and qualitative analysis. Tests for significance were with Student’s t or
chi-square.
Results: Serum deprivation led to a significant increase in superoxide levels in
differentiated RGC-5 cells compared to control cells at 72 hrs (1.73 ± 0.14 vs 1.00 ±
0.02; p<0.001). Analysis of cytochrome c localization along with superoxide levels
showed that the rise in superoxide preceded the release of cytochrome c from the
mitochondrion. Superoxide levels return to basal levels after cytochrome c release,
indicating superoxide’s role as an upstream signaling molecule in the apoptotic
cascade.
Conclusions: Superoxide production in serum-deprived RGC-5 cells is an early signal
in triggering apoptosis. Work is being performed in our laboratory now to determine
the sites of action of superoxide, and ways of preventing or reversing its effects before
caspase activation can occur and cells become committed to an apoptotic fate.
CR: C.J. Lieven, None; K.M. Thurber, None; E.J. Levin, None; L.A. Levin, US
7,303,915, P.
Support: NIH R21EY017970, P30EY016665 and an unrestricted departmental grant
from Research to Prevent Blindness, Inc.
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
3189-3192
Tuesday, May 5, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 3189 - 3200 / D718 - D729
356. Optic Nerve Injury and Regeneration Organizing Section: EY Contributing Section: RE
3193 - D722
Qualitative and Quantitative Analysis of Brn3a Expression in Naïve, Optic
Nerve Transected and Optic Nerve Crushed Adult Rat Retinas
3194 - D723
The Involvement of p53, p63 and p73 in Retinal Ganglion Cell Death After
Axonal, Ischemic and Elevated Intraocular Pressure Injury
F. Nadal-Nicolas, M. Jimenez-Lopez, P. Sobrado-Calvo, L. Nieto-Lopez, I. CanovasMartinez, M. Salinas-Navarro, M. Vidal-Sanz, M. Agudo. Ophthalmology, University
of Murcia, Murcia, Spain.
E.M. Jokinen1A,1B, O. Renko1A,1B, K. Tuppurainen1B, U. Lönngren2, N. Turunen1A,1B,
M. Lafuente3, M. Vidal-Sanz3, F. Hallböök 2, U. Napankangas1A,1B. ADepartment of
Ophthalmology, BDepartment of Pathology, 1Oulu University, Oulu, Finland;
2
Department of Developmental Neuroscience, Uppsala University, Uppsala,
Sweden; 3Department of Ophthalmology, University of Murcia, Murcia, Spain.
Purpose: To characterize Brn3a expression in adult albino rat retina and to quantify
the population of RGCs expressing Brn3a in naïve as well as its temporal loss induced
by intraorbital optic nerve transection (IONT) or crush (IONC).
Methods: Brn3a expression was characterized using morphometric methods. RGCs
were doubly labelled with the regrotrade neuronal tracer Fluorogold applied to both
superior colliculi (SCi), and with antibodies to POU-domain protein Brn3a. Eyes
were extracted at increasing survival intervals (2, 5, 9, or 14 days) after axotomy, and
the retinas were analyzed to determine the population of RGCs positive for Brn3a
and FG.
Results: Brn3a expression was limited to the ganglion cell layer. The percentage of
RGCs positive for FG and Brn3a in naïve retinas was 92,2%. Quantification of the
whole RGC population showed that in naïve retinas there were a mean of 80,251±2210
RGCs-FG+ and 83,449±4541 RGCs-Brn3a+ per retina (mean ±SD; n=14). The temporal
course of RGC-Brn3a+ and RGCs-FG+ loss induced by IONC or IONT followed a
similar trend, however the loss of RGCs-Brn3a+ was significant earlier than the loss
of FG-labelled RGCs.
Conclusions: The great majority of the RGCs-FG+ were also Brn3a+, thus Brn3a can
be used as a reliable and efficient immunocytochemical marker for RGCs in control
and optic nerve injured adult rat retinas. Axotomy induced RGC loss was detected
earlier with Brn3a than with FG.
CR: F. Nadal-Nicolas, None; M. Jimenez-Lopez, None; P. Sobrado-Calvo, None; L.
Nieto-Lopez, None; I. Canovas-Martinez, None; M. Salinas-Navarro, None; M.
Vidal-Sanz, None; M. Agudo, None.
Support: ISCII: CP003/00119, ISCIII PI070225, ISCIII RD07/0062/0001, Fundación
Séneca: 04446/GERM/07 and MECSAF-2005-04812.
Purpose: p53, p63 and p73 are members of the p53 gene family involved in development,
differentiation and cell response to stress. This study was undertaken to determine
their possible involvement in retinal ganglion cell death after experimental injury.
We studied the expression of p53, p63 and p73 mRNA in normal adult rat retina after
optic nerve transection (ONT), selective ligature of ophthalmic vessels (SLOV) and
acute increase in intraocular pressure (IIOP).
Methods: Tissue samples of rat retina were collected 3, 7 and 14 days after ONT and
IIOP, and 24h, 7 and 14 days after SLOV. Total RNA was extracted using Trizol, and
cDNA was synthesized. The expression of target genes was evaluated with quantitative
real-time PCR with SYBR Green assay. Normal, untreated rat retina samples were used
as controls and the relative mRNA expression levels were calculated.
Results: p53, p63 and p73 mRNA was detected in normal adult rat retina. After ONT
the relative level of p53 was increased 1.5-fold at day 7 and p63 mRNA at day 3. p73
mRNA level was increased in all time points, 2-fold at days 3 and 7 and 1.5-fold at
day 14. After SLOV the relative level of p53 mRNA showed 2.5-fold increase at 3 and
7 d and returned to normal by day 14. p63 expression increased 1.5-fold at day 3 and
returned back to normal by day 7. p73 mRNA expression was increased at all time
points. IIOP caused a transient decrease in p53 mRNA level at 24h whereas the relative
level of both p63 and p73 mRNA was found to increase after IIOP.
Conclusions: p63 and p73 expression can be detected from normal adult rat retina. The
alterations in the relative mRNA levels of p53, p63 and p73 suggest that these genes
are involved in retinal ganglion cell death after ONT, SLOV and IIOP.
CR: E.M. Jokinen, None; O. Renko, None; K. Tuppurainen, None; U. Lönngren,
None; N. Turunen, None; M. Lafuente, None; M. Vidal-Sanz, None; F. Hallböök,
None; U. Napankangas, None.
Support: Eye Foundation, Nissi Foundation, Finnish Medical Foundation
3195 - D724
Expression of Matrix Metalloproteinase-7 in Murine Optic Nerve Following
Transection Injury
3196 - D725
Analysis of Cellular and Molecular Associated With Optic Nerve Degeneration
and Regeneration
j. shi, C.-W. Wu, S. Jain, J.-H. Chang, D.T. Azar. Department of Ophthalmology and
Visual Sciences, The university of illinois at Chicago, Chicago, IL.
A.S. Solomon1, S. Rosenzweig2A, A. Nitzan1, A. Barzilai2B. 1Goldschleger Eye Research,
Tel-Aviv University, Tel-Hashomer, Israel; ANeurobiochemistry, BNeurobiology,
2
Tel-Aviv University, Faculty of Life Science, Israel.
Purpose: To determine the expression of matrix metalloproteinases (MMPs) following
murine optic nerve injury.
Methods: Meningeal sparing optic nerve transection were performed in WT mice.
Mice were sacrificed at week one and two, optic nerves were sectioned and confocal
immolocalization was performed for MMP-2, -3, -7 and -14, myelin basic protein (MBP)
and glial fibrillary acidic protein (GFAP). Optic nerve regeneration was examined in
wild type and MMP-7 knock-out mice using DiI tracing.
Results: Immunostaining revealed that MMP-2, MMP-3, and MMP-14 were localized
in the meningeal layers of mouse optic nerve, while MMP-7 was localized within the
optic nerve. MMP-7 expression was increased following optic nerve injury. Double
labeling indicated that MMP-7 is not expressed in oligodendrocytes, but may be
expressed in astrocytes. DiI tracing revealed regeneration of some retinal ganglion
cell axons.
Conclusions: MMP-7 expression is increased after optic nerve transection suggesting
a role for MMPs in scar formation and/or axonal regeneration following optic nerve
injury.
CR: J. shi, None; C.-W. Wu, None; S. Jain, None; J.-H. Chang, None; D.T. Azar,
None.
Support: Research to Prevent Blindness (RPB)
Purpose: To elucidate the regenerative potential of injured optic nerve (ON). We present
the results of a study on the regenerative potential of central nervous system (CNS)
mammalian axons using our unique rat optic nerve model. We analyzed the cellular
and molecular events that control the degenerative and regenerative processes in lower
vertebrates such as goldfish, and mammals, following trauma to optic nerve.
Material and methods: The right optic nerve of adult rats was completely transected
while sparing the vasculature and the meninges. Hyaluronic acid (HA)-based hydro
gel containing supportive factors or self-assembling peptides (SAP) were implanted in
the gap generated by the surgery. Surgery and follow-up were performed according
to the ARVO Rules for Treatment and Care of Animals. Two weeks and one month
following the surgical procedure the animals underwent MRI evaluation of the visual
pathway. Non-injured optic nerve served as positive control and axotomized optic
nerve with no treatment served as negative control.In a parallel set of experiments,
the right optic nerve of adult goldfish was crushed or cut (equal number of fish in
each group) under deep anesthesia. Two weeks and one month following injury,
marker associated with degenerative and regenerative processes were studied in
the optic nerve and retina. We injected intra ocular Semaphorin class 3 to goldfish,
which the optic nerve was injured, to examine whether the degenerative process
could be interrupted.
Results: The regenerative process was traced in vivo using Mn2+ enhancing signal.
The signal in non-injured optic nerve was detected in the retina, optic nerve, optic
tract, lateral geniculate body and visual cortex. The signal in the injured optic nerve
was detected only in the vicinity of the retina and a short proximal stump of optic
nerve. Axotomized ONs that were treated with either HA or SAPs exhibited marked
regeneration of ON. In vitro confocal imaging evaluation confirmed the MRI findings.
Collectively, these results demonstrate the potential of bio-materials scaffolds to
enhance axonal regeneration. We found that administration of Semaphorin class 3
to injured optic nerve of gold fish disrupted the regenerative process of the injured
optic nerve.
Conclusion: The optic nerve of lower vertebrates, such as goldfish, is capable of
regeneration and regain of function while higher mammals, such as rat, require special
modulation of the neuronal environment to enable partial regeneration.
CR: A.S. Solomon, None; S. Rosenzweig, None; A. Nitzan, None; A. Barzilai,
None.
Support: Bi Natural Grant from EC
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
3193-3196
Tuesday, May 5, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 3189 - 3200 / D718 - D729
356. Optic Nerve Injury and Regeneration Organizing Section: EY Contributing Section: RE
3197 - D726
Combination of Transferring CNTF Gene to Retinal Ganglion Cells in vivo
and Transplanting Schwann Cells Grafts Conduct to Enhance the Optic Nerve
Regeneration in Adult Rats
Y. Fang1,2, X. Mo2, W. Guo2, J. Tian2, Y. Wang2, X. Rong2, M. Zhang2, X. Sun2. 1Schepens
Eye Research Institute, Boston, MA; 2Eye & ENT Hospital of Fudan University,
Shanghai, China.
3198 - D727
Characterization of a Novel Photochemically Induced Ischemic Optic
Neuropathy Model
J.L. Goldberg1A, Y. Duan1A, W. Kong1A, M. Benny1A, B. Watson1B. ABascom Palmer Eye
Inst, BNeurology, 1University of Miami, Miami, FL.
Purpose: To promote the injured optic nerve regeneration effectively in the adult
mammalian , transplantation of Schwann cells (SCs) in an artificial grafts combining
with transferring ciliary neurotrophic factor (CNTF) gene to retinal ganglion cells
(RGCs) was tried.
Methods: To provide a suitable axonal growth environment, the tissue engineering
nerve conduct consisting of SCs cultured in poly-lacticco-glycolic acid (PLGA) conduct
was constructed and transplanted to the transected optic nerve stump in adult rats.
Meanwhile, transferring CNTF gene into RGCs in vivo by electroporation was used
to increase the injured RGCs survival and growth capability. Besides that, SCs was
gene-modified in vitro by electroportation to increase their neurotrophic effect. After
4 weeks of transplantation, the effect of axonal regeneration was evaluated by DiI
labeling and GAP43 staining of graft sections.
Results: By electroporation, CNTF gene was transferred to SCs effectively in vitro
which was proven by RT-PCR and immunocytochemistry. The tissue engineering nerve
conduct was good biocompatible and held abundant of SCs. Transplantation of CNTF
gene modified SCs grafts promoted more axons to regenerate than SC grafts. And With
the combinational therapy of transferring CNTF into RGCs in vivo by electroporation,
transplantation of CNTF gene modified SCs grafts can reach the best effect.
Conclusions: The combinational use of genetically modified tissue engineering nerve
conduct to bridge tissue defects and transferring neurotrophic factor gene to RGCs to
enhance its intrinsic survival and regenerative capacity may provide new therapeutic
strategies for the treatment of optic nerve injuries.
CR: Y. Fang, None; X. Mo, None; W. Guo, None; J. Tian, None; Y. Wang, None; X.
Rong, None; M. Zhang, None; X. Sun, None.
Support: National Natural Science Fund of China Grant NSFC30300379, Natural
Science Fund of Shanghai Grant 034119807
Purpose: The mechanisms that lead to neuronal death after axonal injury are poorly
understood partly due to the lack of clinically relevant animal models. Here we are
using a novel photochemically induced ischemic optic neuropathy (PCI-ION) model
to better understand optic nerve stroke.
Methods: The left optic nerve from Sprague-Dawley (SD) adult rats was exposed to
532 nm Nd:YAG laser irradiation delivered as high-intensity pulses for 90 seconds
immediately after the photosensitizing dye Erythrosin B (ErB) was injected through
the femoral vein. Evans blue was used to characterize the vessel leakage and thrombus
formation in the optic nerve and DiA was used to check the integrity of retinal
circulation. The histological changes after PCI-ION was examined by both H&E
staining and immunohistochemistry. RGC survival was quantified by counting the
number of retrogradely labeled flurogold-positive cells in the flat mounted retina.
Results: PCI-ION led to vessel leakage indicated by Evans blue distribution outside of
the vessels in the nerve without interfering the circulation of retina by DiA perfusion.
One week after PCI-ion at 200mw intensity, H&E staining of the optic nerve cross
sections demonstrated that the optic nerve structure was disrupted and cells were
aggregated at the treated area (~700μm in length, 2/3 in depth). Immunohistochemistry
revealed that PCI-ION led to glial cell activation. PCI-ION led to retrograde cell death
in the corresponding retinal quadrant.
Conclusions: We have successfully generated a rodent model of ischemic optic
neuropathy. With this model, we can explore in depth the mechanisms leading to
neuronal death after axonal injury, and eventually test new therapeutic strategies
to enhance survival.
CR: J.L. Goldberg, None; Y. Duan, None; W. Kong, None; M. Benny, None; B.
Watson, None.
Support: American Heart Association (JLG), James and Esther King Foundation
(JLG), NEI P30 EY014801 (UM), and an unrestricted grant from Research to Prevent
Blindness.
3199 - D728
In vivo Imaging of Retinal Ganglion Cell Axons Within the Nerve Fiber Layer
3200 - D729
Relevance of 24S-Hydroxycholesterol as a Biomarker of Optic Neuropathies
A. Kanamori, M.-M. Catrinescu, M. Traistaru, R. Beaubien, L.A. Levin. Ophthalmology,
University of Montreal, Montreal, QC, Canada.
L. Bretillon1, L. Martine1, B. Pasquis1, C. Fourgeux1, C. Schnebelen1, N. Acar1, I. Björkhem2,
A.M. Bron1,3, C.P. Creuzot-Garcher1,3. 1INRA, University of Burgundy, Eye &
Nutrition Research Group, Dijon, France; 2Department of Laboratory Medicine,
Karolinska Institutet, Stockholm, Sweden; 3University Hospital, Department of
Ophthalmology, Dijon, France.
Purpose: Optic nerve injury causes the loss of retinal ganglion cells (RGCs) and their
axons. The reduction in RGC counts over time in axonal injury is well studied, but the
correlation with the time course of anterograde and retrograde axonal degeneration
is less clear. We longitudinally observed retinal nerve fiber bundles (RNFB) stained
with a chloromethyl derivative of fluorescein diacetate (CMFDA) in the living rat
after optic nerve injury.
Methods: The right optic nerves of Long-Evans rats were transected within the
meninges by a transconjunctival approach, sparing the retinal circulation. Three days
after transection CMFDA was intravitreously injected to a vitreous concentration
of 60 µM. Confocal scanning laser imaging was performed daily with a Heidelberg
Retina Angiograph 2 (HRA2) using the fluorescein channel and images exported to
ImageJ. Mean fluorescence intensity and number of CMFDA bundles were calculated.
A separate group of animals underwent retrograde RGC labeling by overlaying the
superior colliculi with Alexa Fluor 488-dextran.
Results: RNFB lost 87 ± 15% of their fluorescence by 7 days after injection and 10
days after optic nerve transection, compared with 42 ± 26 % in untransected eyes
(p = 0.005, n = 6). Similarly, the number of labeled RNFB decreased by 86 ± 13 %
after optic nerve transection, vs. 49 ± 22 % in untransected eyes (p = 0.004; n = 6). To
distinguish increased leakage of CMFDA as a result of injury from decreased number
of CMFDA-positive axons, another group of animals were injected with CMFDA at 2
and 3 weeks after transection. There were far fewer axon bundles labeled, compared
to the number labeled at three days after transection, consistent with a decrease in
the number of axons and not just CMFDA leakage. The number of retrograde labeled
RGC bodies and CMFDA bundles on HRA2 decreased rapidly between 5 and 7 days
after transection.
Conclusions: Intravitreal CMFDA can be used to longitudinally monitor RGC axons
within the retinal nerve fiber layer in vivo.
CR: A. Kanamori, None; M.-M. Catrinescu, None; M. Traistaru, None; R. Beaubien,
None; L.A. Levin, None.
Support: Canada Institutes for Health Research, Canada Foundation for Innovation,
Canada Research Chairs program, Fonds de recherche en ophtalmologie de l’Université
de Montréal
Purpose: 24S-Hydroxycholesterol is formed by enzymatic oxidation of cholesterol via
cholesterol-24S-hydroxylase (CYP46A1) activity in neurons, including retinal ganglion
cells and neurons from the inner retina. We investigated whether neurodegeneration
could be associated with the release of 24S-hydroxycholesterol in acute neuropathies,
and therefore 24S-hydroxycholesterol could be considered as a biomarker of retinal
cell degeneration in the course of optic neuropathies.
Methods: Retinal neurodegeneration was induced in rats by severe elevation of intraocular pressure. For that purpose, rats were submitted to 532nm-laser photocoagulation
of the episcleral veins, limbus and trabecular meshwork. Intra-ocular pressure was
monitored in a time course study at 1, 3, 7, 14, 21, 30 and 60 days post laser injury using
Tonolab®. Rat retinal and plasma 24S-hydroxycholesterol levels were quantified by
gas-chromatography mass spectrometry using deuterated internal standard at the
same time points. Plasma levels of 24S-hydroxycholesterol were similarly monitored
in patients suffering from anterior ischemic optic neuropathy.
Results: Intra-ocular pressure was significantly raised by a factor of five in the
laser treated-eyes of the rats compared to fellow eyes, during the first two weeks
after photocoagulation, and returned to baseline afterwards. The levels of
24S-hydroxycholesterol were lowered in the first three days in the retina injured by
laser, compared to fellow eye. Meanwhile, plasma levels of 24S-hydroxycholesterol
were raised by a factor of three. Patients suffering from anterior ischemic optic
neuropathy showed increased plasma levels of 24S-hydroxycholesterol, compared to
age-matched normal subjects (H=6.86, P=0.009 by Kruskal-Wallis test).
Conclusions: Increased plasma levels of 24S-hydroxycholesterol were associated
with acute phases of optic neuropathies, suggesting its relevance as a biomarker of
retinal neurodegeneration.
CR: L. Bretillon, None; L. Martine, None; B. Pasquis, None; C. Fourgeux, None; C.
Schnebelen, None; N. Acar, None; I. Björkhem, None; A.M. Bron, None; C.P. CreuzotGarcher, None.
Support: PHRC inter-régional Dijon-Nancy
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
3197-3200
Tuesday, May 5, 3:45 PM - 5:30 PM Palm A Paper Session Program Number Range: 3463 - 3469
368. Retinal Ganglion Cell Injury and Regeneration Organizing Section: EY
3463 - 3:45PM
Eary Changes in Experimental Anterior Ischemic Optic Neuropathy and
Treatment with α-B Crystallin
3464 - 4:00PM
In vivo Confocal Scanning Laser Imaging of Retinal Ganglion Cell Superoxide
After Optic Nerve Transection
Y.J. Liao1A, K. Kaur1A, S. Ousman2, L. Steinman1B, S. Pangratz-Fuehrer1A.
A
Ophthalmology, BNeurology, 1Stanford, Stanford, CA; 2Clinical Neurosciences,
University of Calgary, Calgary, AB, Canada.
M.-M. Catrinescu1, A. Kanamori1, K.A. Mears1, R. Beaubien1, L.A. Levin1,2.
1
Ophthalmology, Maisonneuve Rosemont Hospital Research Center, University of
Montreal, Montreal, QC, Canada; 2Ophthalmology and Visual Sciences, University
of Wisconsin, Madison, WI.
Purpose: Anterior ischemic optic neuropathy (AION) is due to ischemia of the optic
nerve head, leading to significant vision loss. Our goal was to study the early changes
following optic nerve head ischemia and to test the efficacy of a potential therapy
in experimental AION.
Methods: We used a photochemical thrombosis model of AION in mouse, with laserdirected optic nerve head ischemia in the presence of rose bengal. Intracranial flash
visual evoked potential (fVEP) recordings and histological methods were utilized.
Results: Within days after experimental AION, there was significant optic nerve head
swelling, vascular leakage, and selective loss of the peri-papillary microvasculature.
Consistent with these ischemic changes, there was functional impairment as
demonstrated by a decrease in the amplitude of fVEP responses. Coincident with
these histological and functional deteriorations, there were signs of inflammatory
cellular reactions, with up-regulation of macro- and microglia. Interestingly, the
expression of α-B crystallin (αBC), a small heat shock protein abundant in the lens
of the eye, was significantly increased in the optic nerve head and retina at day one
following experimental AION. This led us to test αBC as a potential treatment in
experimental AION. Injected daily for 3 days following optic nerve head ischemia,
αBC did not dampen post-ischemic macro- and microglial responses in wild-type
or in αBC knock-out mice. Since significant retinal ganglion cell loss occurs within
the first 3 weeks following experimental AION, leading to irreversible vision loss,
we tested the effects of a 3-week course of αBC, with weekly fVEP measurements
to monitor visual function. After 3 weeks of αBC treatment, there was a significant
improvement of the fVEP latencies in the αBC-treated group but not in the salinetreated group, without an improvement in the fVEP amplitudes or the number of
surviving retinal ganglion cells.
Conclusions: αBC, an important chaperone and key molecule in inflammation and
neurodegeneration, was acutely up-regulated in experimental AION. Short-term αBC
treatment immediately following optic nerve head ischemia did not have significant
effects, while a 3-week course of αBC injections led to a dramatic improvement of
the visual pathway signal transmission, consistent with a mechanism of axonal
protection.
CR: Y.J. Liao, None; K. Kaur, None; S. Ousman, P, P; L. Steinman, P, P; S. PangratzFuehrer, None.
Support: Career Award in Biomedical Sciences from the Burroughs Wellcome
Foundation, NIH Grant K08 NS044268
Purpose: We previously used in vitro and ex vivo imaging to demonstrate generation
of superoxide within axotomized retinal ganglion cells (RGCs). We now describe the
use of longitudinal in vivo imaging to study superoxide within retinal ganglion cells
after optic nerve transection.
Methods: The right optic nerves of Long-Evans rats were transected within the
meninges by a transconjunctival approach, sparing the retinal circulation. Both eyes
were intravitreously injected with hydroethidine (HEt), which reacts with superoxide
to form a fluorophore with a distinct emission profile, to a final concentration of 100 µM.
Retinal ganglion cells (RGCs) were identified with retrograde labeling by overlaying
the superior colliculi with DiR (20 mg/ml). Confocal scanning laser imaging was
performed with a Heidelberg Retina Angiograph 2 (HRA2) using the fluorescein
channel for HEt and the indocyanine green channel for DiR.
Results were confirmed by immunohistofluorescence.
Results: HEt-positive cells could be imaged in vivo within the ganglion cell layer 1
day after optic nerve transection. The number of HEt-positive cells increased to a
maximal level 4 days after transection. HEt-positive cells were not present in eyes
untransected eyes. HEt-positivity co-localized with RGCs retrograde labeled with
DiR. Intravitreal pegylated superoxide dismutase significantly reduced the number
of HEt-positive cells (40.6 ± 18.5 vs. 4.8 ± 6.3; p < 0.001).
Conclusions: An increase in RGC superoxide can be identified by confocal scanning
laser ophthalmoscopy at an early stage after axonal injury.
CR: M.-M. Catrinescu, None; A. Kanamori, None; K.A. Mears, None; R. Beaubien,
None; L.A. Levin, None.
Support: Canadian Institutes for Health Research, Canadian Foundation for
Innovation, Canadian Research Chairs program, Fonds de recherche en ophtalmologie
de l’Université de Montréal
3465 - 4:15PM
Manipulation of Intrinsic Growth Control Pathways to Promote CNS Axon
Regeneration-Involvement of PTEN/mTOR Pathway
3466 - 4:30PM
Enhanced Retinal Axonal Sprouting Following Optic Nerve Crush in Adult
CCL2 Deficient Mice
K.S. park, K. Liu, Y. Hu, P. Smith, C. Wang, B. Cai, B. Xu, I. Kramvis, M. Sahin, Z. He.
Neurology, Children’s Hospital Boston, Boston, MA.
K.-S. Cho, D.-F. Chen. Schepens Eye Research Institute, Department of
Ophthalmology and Program in Neuroscience, Harvard Medical School, Boston,
MA.
The failure of axons to regenerate is a major obstacle for functional recovery after
central nervous system (CNS) injury. Removing extracellular inhibitory molecules
results in limited axon regeneration in vivo. To test for the role of intrinsic impediments
to axon-regrowth, we analyzed cell growth control genes using a virus-assisted in
vivo conditional knockout approach. Deletion of PTEN (phosphatase and tensin
homolog), a negative regulator of the mammalian target of rapamycin (mTOR) pathway,
in adult retinal ganglion cells (RGCs) promotes robust axon regeneration after optic
nerve injury. In wild-type adult mice, the mTOR activity was suppressed and new
protein synthesis was impaired in axotomized RGCs, which may contribute to the
regeneration failure. Reactivating this pathway either by conditional knockout of
tuberous sclerosis complex 1 (TSC1), another negative regulator of the mTOR pathway
or over-expression of Ras homologue enriched in brain 1 (Rheb1), a direct activator
of mTOR pathway also leads to axon regeneration. Thus, our results suggest the
manipulation of intrinsic growth control pathways as a therapeutic approach to
promote axon regeneration following CNS injury.
CR: K.S. park, None; K. Liu, None; Y. Hu, None; P. Smith, None; C. Wang, None; B.
Cai, None; B. Xu, None; I. Kramvis, None; M. Sahin, None; Z. He, None.
Support: Craig H Neilson Foundation
Purpose: Injured CNS including optic nerve has been known of incapable to regenerate
the injured axons in adult mammal. In addition to the known astrocyte- and myelinrelated growth inhibitors along CNS pathway, the infiltration of leucocytes may play
a role to block optic nerve regeneration. It has been shown that upregulation of CCL2
would regulate infiltration of leucocytes into the lesion area. To test this hypothesis,
we performed optic nerve crush in adult C57BL/6J and CCL2 knockout mice and
compare the axonal regrowth after injury.
Methods: Optic nerve crush was performed in adult CCL2 knockout and C57BL/6J
(background-matched control) mice. On day 11 post-injury, 2 μl of an anterograde axon
tracer, cholera toxin B subunit (CTB), was injected into the vitreous of the operated
eye. On day 14 post-injury, mice were sacrificed and optic nerves were collected and
processed for cryosections. To determine axonal regrowth, the sections were incubated
with goat anti-CTB antibody, followed by secondary antibody of biotinylated antigoat IgG, and were visualized by Alexa Fluor 546. To determine retinal ganglion cell
survival, retinal sections were incubated with primary antibody against beta-IIItubulin and 4’, 6-diamidino-2-phenylindole (DAPI). Number of CTB-positive axons
that regenerated past the lesion site was counted at steps of 250 μm away from the
crushed site in optic nerve sections. Numbers of beta-III-tubulin- and DAPI-positive
cells in the ganglion cell layer were counted in 5 random and non-overlapping areas
in each retinal section under 400x magnifications.
Results: Little axonal regeneration was observed in wild-type mice. However, absence
of CCL2 significantly improved axonal regrowth after optic nerve injury in CCL2
knockout mice as compared to wild-type mice, and the number of regenerating
axons counted from CCL2 knockout mice was ten times more than was observed
in wild-type mice.
Conclusions: Absence of CCL2 provides a permissive environment for axonal
sprouting, likely through the suppression of injury-induced activation of microglia
and macrophages.
CR: K.-S. Cho, None; D.-F. Chen, None.
Support: NIH/NEI R01EY017641, Department of Defense W81XWH-04-2-0008, the
American Health Foundation, P30 EY003790 (Core grant to the Schepens Eye Research
Institute).
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
3463-3466
Tuesday, May 5, 3:45 PM - 5:30 PM Palm A Paper Session Program Number Range: 3463 - 3469
368. Retinal Ganglion Cell Injury and Regeneration Organizing Section: EY
3467 - 4:45PM
Tnfr1 Death-Signalling Pathway Is Regulated in the Retina Both After Optic
Nerve Transection and Optic Nerve Crush
3468 - 5:00PM
Genome-Wide Transcription Profile in Leukocytes of LHON Patients With the
11778 Mutation
M. Agudo, F. Nadal-Nicolas, M. Perez-Marin, P. Sobrado-Calvo, L. Nieto-Lopez, M.
Salinas-Navarro, M. Vidal-Sanz. Oftalmologia, Universidad de Murcia, Murcia,
Spain.
T.M. Bosley1,2, K.K. Abu-Amero1. 1Ophthalmology, King Saud University, Riyadh,
Saudi Arabia; 2Medicine, Cooper University Hospital, Camden, NJ.
Purpose: We have previously demonstrated that TNFR1 and TRADD are up-regulated
in optic nerve injured retinas and expressed by axotomized retinal ganglion cells
(RGCs) (Agudo et al, Mol Vision 2008, 14:1050-63). Here we further analyse the temporal
regulation of FADD and Caspase 8, adaptor and effectors downstream the TNFR1
death signalling pathway, in retinas undergoing intraorbital optic nerve transection
(IONT) or crush (IONC)
Methods: In control adult albino rats and in ON injured retinas analyzed at 12h, 48h
or 7d after IONT or IONC (n=4, per treatment and time point), retinas were either
freshly dissected for protein extraction and western blotting, or perfused, frozen
and cut on the cryostat on 15µm thick radial sections. RGCs were identified with
Fluorogold (FG) applied to both superior colliculi (SCi) one week before ON injury.
Sections and westerns were incubated with primary antibodies against FADD and
Caspase 8, and revealed with secondary antibodies conjugated to alexa-568 and
HRP, respectively.
Results: Western blotting assays revealed that Caspase 8 precursor and active
forms, and FADD were up-regulated as soon as 12h post-IONT and IONC This upregulation is maintained up to 7dpl. This up-regulation is maintained up to 7dpl.
Immunohistofluorescence to radial sections of control and injured retinas showed
that both proteins were expressed by RGCs as seen by their co-localization with FG,
among other cells of the ganglion cell later. Western blotting assays revealed that
Caspase 8 precursor and active forms, and FADD were up-regulated as soon as 12h
post-IONT and IONC.
Conclusions: The up-regulation of FADD and Caspase 8 after optic nerve injury
further implies an active role for the extrinsic apoptotic pathway triggered by TNFR1
in signalling axotomy induced RGC death.
CR: M. Agudo, None; F. Nadal-Nicolas, None; M. Perez-Marin, None; P. SobradoCalvo, None; L. Nieto-Lopez, None; M. Salinas-Navarro, None; M. Vidal-Sanz,
None.
Support: ISCII: CP003/00119, ISCIII PI070225, ISCIII RD07/0062/0001, Fundación
Séneca: 04446/GERM/07 and MECSAF-2005-04812
Purpose: We evaluated gene expression in leukocytes of four patients with the 11778
mitochondrial DNA mutation and bilateral optic neuropathy consistent with Leber
hereditary optic neuropathy (LHON) and three age, sex, and ethnicity matched
controls in order to examine the altered expression of mitochondrial and nuclear genes
associated directly or indirectly with mitochondria or the oxidative phosphorylation
machinery and to see if a unique gene expression profile could be obtained for
LHON.
Methods: RNA was extracted from leukocytes and cDNA reverse transcribed and
hybridized to Affymetrix Gene Chips. Principle component analysis and the Rate
Monotonic Algorithm were performed and further analysis applied to genes with a
2-fold expression difference and p < 0.005 between patients and controls.
Results: The gene expression profile of patients with the 11778 mtDNA mutation was
significantly different from controls. With the aid of the Gene Ontology Database,
the most commonly up-regulated genes (n = 137) were found to be related to the
cellular transport (13.8%; 19/137) and transcription (12.4%; 17/137). Similarly, the
most commonly down-regulated genes (n = 152) were also related to the cellular
transport (17.8%; 27/152) and transcription (18.4%; 28/152). Surprisingly, none of the 13
mitochondrial coded genes and no structural mitochondrial nuclear-encoded genes
were differentially expressed. The OPA1 gene was down-regulated, but no other nonstructural nuclear-encoded mitochondrial gene was differentially expressed.
Conclusions: The presence of the 11778 mtDNA
mutation resulted in a unique gene expression
profile compared to controls together with
changes in transcription of specific genes that
may provide information about LHON disease
mechanisms. In particular, down-regulation of
OPA1 could be integral to the mitochondriainduced apoptosis that is likely the pathologic
process in LHON.
CR: T.M. Bosley, None; K.K. Abu-Amero,
None.
Support: None
3469 - 5:15PM
Axonal mtDNA Copy Number Correlates With the Neurodegenerative Pattern
in Optic Nerve Cross-Sections of Leber’s Hereditary Optic Neuropathy Patients
V. Carelli1, F.N. Ross-Cisneros2, M. Sebastiani 3, C. Travaglini 3, S.S. Salomao 4, A.
Berezowski4, M. Moraes5, M.F. Moraes5, A.A. Sadun2, C. Giordano3. 1Neurological
Sciences, University of Bologna, Bologna, Italy; 2Doheny Eye Institute, University
of Southern California Keck School of Medicine, Los Angeles, CA; 3Experimental
Medicine, University La Sapienza, Rome, Italy; 4Ophthalmology, Federal University
Sao Paolo, Sao Paolo, Brazil; 5Ophthalmology, Instituto de Olhos de Colatina,
Colatina, Espirito Santo, Brazil.
Purpose: To describe the correlation between axonal mtDNA amount and pattern of
neurodegeneration in optic nerve cross-sections from control and Leber’s hereditary
optic neuropathy (LHON) individuals. LHON, a blinding disorder due to mtDNA point
mutations affecting complex I, is characterized by selective neurodegeneration of retinal
ganglion cells (RGCs). Increased mitochondrial biogenesis is described as a compensatory
mechanism in LHON and mtDNA copy number may be relevant for RGCs loss.
Methods: We investigated 12 eyes from six controls and 4 eyes from two LHON/11778
patients, collected at autopsy. Retrobulbar optic nerve 5 μm thick cross-sections were
stained with Luxol Fast Blue and nerve bundles from temporal, superior, nasal, inferior,
and central regions were microdissected by laser capturing. Microdissected areas were
measured (μm 2) and subjected to histomorphometric analyses (Metamorph 6.0) to count
glial cells. Total DNA was extracted and mtDNA amount was quantified by Real-TimePCR. The number of mtDNA molecules were normalized as mtDNA copy/μm3 (area x
5 μm) or as mtDNA copy/nucleus (glial cells). Pattern of degeneration was evaluated in
the LHON optic nerves by immunostaining with antibodies against myelin basic protein
and by paraphenylenediamine staining.
Results: Content of mtDNA per μ3 in temporal and central regions was significantly lower
(p<0.05) than the superior, nasal and inferior regions. Similar results were observed for
mtDNA/nucleus ratio. These results fit the profile of neurodegeneration seen in optic
nerve cross-section from the LHON patients, where a “butterfly-like” pattern of axonal
loss affects first the temporal quadrant, eventually expanding into the superior/inferior
quadrants and leaving the nasal the most spared.
Conclusions: This study demonstrates that the papillomacular bundle axons of the
temporal quadrant are the most vulnerable having the lowest amount of mtDNA.
These observations support the proposal that mtDNA copy number is relevant to
neurodegeneration of RGCs and increase of mitochondrial biogenesis may be a successful
compensatory mechanism.
CR: V. Carelli, None; F.N. Ross-Cisneros, None; M. Sebastiani, None; C. Travaglini,
None; S.S. Salomao, None; A. Berezowski, None; M. Moraes, None; M.F. Moraes,
None; A.A. Sadun, None; C. Giordano, None.
Support: Telethon Grant GGP06233 to VC
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
3467-3469
Wednesday, May 6, 8:30 AM - 10:15 AM Palm A Symposia Program Number Range: 3862 - 3865
402. Suppression in Strabismus and Amblyopia - Minisymposium Organizing Section: EY Contributing Section: VI
3862 - 8:30AM
A Million Neurones Can Be Wrong.
3863 - 8:40AM
The Measurement And Treatment Of Suppression
R.A. Harrad. Ophthalmology, Bristol Eye Hospital, Bristol, United Kingdom.
R.F. Hess. Ophthalmology, McGill University, Montreal, QC, Canada.
In amblyopia much of the visual input of the amblyopic eye, amounting to about one
million ganglion cell axons, is suppressed during binocular viewing. I shall introduce
this symposium by outlining some of the physiological processes that are thought to
be instrumental in bringing about this powerful effect and briefly summarise some
of the experimental evidence that has been gathered in over 100 years of activity in
this field of research.
CR: R.A. Harrad, None.
It has been established that in amblyopia, information from the amblyopic eye
(AME) is not combined with that from the fellow fixing eye (FFE) under conditions
of binocular viewing. However, recent evidence suggests that mechanisms that
combine information between the eyes are intact in amblyopia. The lack of binocular
function is most likely due to the imbalanced inputs from the two eyes under binocular
conditions (Baker, Meese, Mansouri & Hess, 2007b). We have measured the extent to
which the information presented to each eye needs to differ for binocular combination
to occur and in doing so we quantify the influence of interocular suppression. We
quantify these suppressive effects for suprathreshold processing of global stimuli
for both motion and spatial tasks. The results confirm the general importance of
these suppressive effects in rendering the structurally binocular visual system of a
strabismic amblyope, functionally monocular.
CR: R.F. Hess, None.
3864 - 9:10AM
Neural correlates of suppression
3865 - 9:40AM
Mapping of Visual Field Suppression in Strabismus
A.M. Norcia. Smith-Kettlewell Eye Res Inst, San Francisco, CA.
J.C. Horton. Ophthalmology, Univ California - San Francisco, San Francisco, CA.
Due to the misalignment of their eyes during early development, most strabismic
observers have no functional stereopsis. Nevertheless, they do have binocular
interactions, primarily of a suppressive or inhibitory kind. We have used the Visual
Evoked Potential to explore the electrophysiological characteristics of suppression
in strabismic patients with and without anisometropia. We find evidence consistent
with strabismic suppression being a component of an aberrant stereo network that
when operative, prevents diplopia in the absence of stereopsis. We have also found a
special case where suppression fails in a disparity-dependent fashion.
CR: A.M. Norcia, None.
We mapped regional patterns of perceptual suppression by testing the visual
fields dichoptically in 9 strabismic humans with no history of diplopia (3 esotropes
and 6 exotropes). Subjects wore red/blue dichroic filter goggles to allow dichoptic
stimulation. They fixated a monocularly seen (red or blue) central target rear-projected
onto a translucent tangent screen. Without breaking fixation, subjects were asked
to identify the apparent color of a peripheral stimulus flashed briefly (200 ms) on
the screen. The peripheral stimulus was purple; its reported color (“red” or “blue”)
revealed which eye’s image was perceived at that locus. The position of each eye was
monitored continuously with infrared video eye trackers to insure accurate fixation
on the central target and to monitor the location of the deviated eye. Using this
perimetric technique, we generated a perceptual map for each eye under conditions
of binocular stimulation. Normal control subjects, rendered diplopic with a prism,
reported two stimuli (red and blue) at all retinal locations except at their blind spots.
In contrast, the strabismic subjects reported a single stimulus (either red or blue) at
the majority of field locations. Their binocular maps showed regional perceptual
suppression and dominance for each eye.
CR: J.C. Horton, None.
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
3862-3865
Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204
415. Neuro-Ophthalmology Organizing Section: EY
4017 - A179
An Analysis of Patient Clinical and Laboratory Characteristics in Relation to
Temporal Artery Biopsy Results
4018 - A180
Biopsy Positive Temporal (Giant-cell) Arteritis - Is a Higher Inflammatory
Response Associated With Visual Loss?
M.R. Melson, L.A. Mawn. Ophthalmology, Vanderbilt Eye Institute, Nashville, TN.
S. Trikha, A. Lockwood, J. Kirwan. Ophthalmology Department, Portsmouth, UK,
Portsmouth Hospitals’ NHS Trust, Portsmouth, United Kingdom.
Purpose: Clinical signs, symptoms and elevated serum inflammatory markers may
support the diagnosis of giant cell arteritis (GCA), but a positive temporal artery biopsy
(TAB) is often considered paramount in confirming it. Physicians must ultimately use
clinical judgment in choosing patients on whom to perform TAB, but laboratory and
other objective data may help support this decision. We examined our institutional
experience over the past 10 years to help determine what patient characteristics were
most associated with a positive TAB.
Methods: After institutional review board approval, we obtained the list of all patients
at our institution that had undergone TAB from 1997-2008. Data on demographics,
indications for TAB, relevant laboratory values, surgical service, biopsy specimen
length, and biopsy results were collected from the patients’ charts. Data were analyzed
to determine if there were significant differences in the clinical and laboratory
characteristics of patients with different biopsy results.
Results: Two hundred patients underwent TAB or ligation in the study period. Twentyfour patients were excluded for insufficient data or because the procedure was not
performed to evaluate for GCA. Of the 176 biopsies included, 26 (15%) were positive
and 154 (85%) were negative. The mean age of patients with a positive TAB was 74
and of those with negative biopsies, it was 68 (p=0.004). Among patients with positive
TAB, 69% were female and 31% were male while the distribution for patients with a
negative biopsy was 73% and 27%, respectively. The mean erythrocyte sedimentation
rate (ESR) for patients with a positive biopsy was 82 mm/hr and that for patients with
a negative biopsy was 60 mm/hr (p=0.0005). The average length of positive biopsy
specimens was 2.8 cm and that for negative specimens was 3.3 cm (p=0.19).
Conclusions: Older age and higher sedimentation rates are correlated with a greater
likelihood of a positive TAB in patients suspected of having GCA. Though more
women undergo TAB, the proportion of men and women with positive biopsies is
not significantly different. Longer TAB specimens were not correlated with a higher
likelihood of a positive pathologic diagnosis.
CR: M.R. Melson, None; L.A. Mawn, None.
Support: Research to Prevent Blindness unrestricted departmental grant
4019 - A181
Six-Year Results of a Protocol for the Early Diagnosis of Temporal Arteritis in an
Ophthalmological Setting
E. Heron, A. Affortit-Demoge, I. Rossignol, N. Sedira, S. Feldman-Billard. Service de
Medecine Interne, CHNO des Quinze-Vingts, Paris, France.
Purpose: Preventing ocular complications remain the main goal of the treatment of
temporal arteritis (TA). We reviewed our last 6-year experience of TA-related ocular
manifestations at a national eye center, and of our diagnostic strategy for TA.
Methods: Retrospective study of medical records: since august 2001, all patients with
ischemic ocular manifestations potentially related to TA had C-reactive protein and
erythrocyte sedimentation rate measured in emergency, their ocular and general
manifestations were recorded by an internist. Patients older than 55 years with
acute anterior ischemic optic neuropathy (AAION) systematically had temporal
artery biopsy, whereas those with other ocular manifestations qualified for a biopsy
in the presence of systemic signs and/or laboratory abnormalities. The diagnosis of
TA was based on histological signs, or in presence of a high level of clinical and/or
biological suspicion.
Results: Between august 2001 and september 2007, a temporal artery biopsy was done
in 305 patients, 265 of them (87%) with AAION. A diagnosis of TA was made in 82
patients (27%), biopsy-proven in 59 of them (72%) and despite a negative biopsy in 23
(28%). Among these 82 patients, 71 (86%) had a definitive vision loss due to AAION
in 67 (82%) and to central retinal artery occlusion in 4 (5%), whereas 11 (13%) had
only transient ocular manifestations (6 had diplopia and 5 had transient monocular
blindness) which didn’t progress to a definitive vision loss after steroid treatment
(pulse methylprednisolone). Among patients with AAION, a positive biopsy was
obtained in 47 cases, of whom 11 (23%) had occult TA (no systemic sign or symptom)
and 3 (6%) had normal laboratory parameters before steroid treatment.
Conclusion: Making an early diagnosis of TA in patients older than 55 years in front
of transient ocular ischemic manifestations, or by systematic temporal artery biopsy
in those with AAION, is not a rare opportunity and is efficient to prevent further
vision loss.
CR: E. Heron, None; A. Affortit-Demoge, None; I. Rossignol, None; N. Sedira,
None; S. Feldman-Billard, None.
Support: None
Purpose: To investigate the correlation with inflammatory markers of patients with
biopsy proven Temporal Arteritis. Secondary outcomes were to assess socioeconomic
status and overall incidence
Methods: All patients referred for Temporal Artery biopsy at a single centre over a
three year period were included. Inflammatory markers Erythrocyte Sedimentation
Rate (ESR), C-Reactive Protein (CRP) and serum platelet count were compared between
biopsy positive and negative samples, along with visual loss and no visual loss groups.
Index of deprivation scores from the national database were compared to a cataract
surgery group (control) to determine socioeconomic status.
Results: Biopsy positive age adjusted incidence was 29.3/100000. 111 Temporal
Artery biopsies were performed; 33 were positive cases (B+ve) and 78 negative for
GCA(B-ve). Mean age at biopsy was 74.5 years. 93% of cases referred for biopsy were
subsequently diagnosed with GCA on clinical grounds. Mean CRP was 50.75 in the
B-ve group versus 98.0 in the B+ve group (p<0.001), and mean ESR was 53.9 (B-ve)
versus 69.9 (B+ve) (p<0.018). Mean platelet count was 359.7 (B-ve) compared to 438.8
(B+ve) (p<0.001). A higher inflammatory response was not observed in B+ve visual
loss group versus B+ve no visual loss (p <0.847, Mann Whitney U test). Statistically
insignificant differences in socioeconomic status were found in biopsy positive group
compared to controls (p=0.112)
Conclusions: Biopsy positive GCA was associated with significant elevations in serum
platelet count, ESR and CRP levels compared to biopsy negative GCA, although visual
loss in positive samples did not appear to correlate with inflammatory marker levels.
GCA appears unrelated to socioeconomic status in this cohort. A large proportion
of biopsies were negative or inconclusive - warranting strict criteria for biopsy
referral.
CR: S. Trikha, None; A. Lockwood, None; J. Kirwan, None.
Support: None
4020 - A182
Asymptomatic Papilledema in Morbidly Obese Patients: A Prospective Study
D.G. Chu, W. Smith, C.M. Krispel, M.R. Ali, J.L. Keltner. Ophthalmology, UC Davis
Medical Center, Sacramento, CA.
Purpose: Idiopathic Intracranial Hypertension (IIH) is associated with obesity,
however when asymptomatic, IIH is difficult to diagnose in a primary care setting
because its sentinel finding is papilledema. Asymptomatic IIH has been estimated
in some populations to be as high as 5%-24%. It is unknown if previously proposed
screening for asymptomatic IIH based on previously published rates of asymptomatic
IIH can be validated by a similarly high incidence of asymptomatic IIH in morbidly
obese patients. The purpose of this study was to determine the rate of asymptomatic
papilledema found on non-mydriatic fundus imaging of morbidly obese patients in
a bariatric surgery clinic.
Methods: This was a prospective study. All morbidly obese patients (BMI >35) seeking
bariatric surgery who consented to the study and had no visual opacity preventing a
high quality fundus photo were included. Non-mydriatic fundus images were taken
by trained clinic personnel. Images were reviewed by an ophthalmologist, and optic
nerves were evaluated for papilledema. Patients suspected of having an optic nerve
abnormality had a subsequent clinical exam by a neuro-ophthalmologist.
Results: 140 patients met the inclusion criteria for the study, 83.8% were female, with
a mean age of 44.9 years. The mean BMI was 47.8. Ocular abnormalities were noted
in 6 patients. Only one patient had subtle bilateral optic disc edema and referred for
full neurological IIH work-up. Other findings included optic nerve hyaloid remnant,
optic nerve drusen, epiretinal membrane, congenital macular scar, and proliferative
diabetic retinopathy. The rate of ocular pathology found in our study was 4.3% (6
of 140 patients). The rate of asymptomatic papilledema in our study was 0.7% (1 of
140 patients).
Conclusions: The non-mydriatic camera can be used successfully in the primary care
setting to detect even subtle optic disc edema. Many undiagnosed ocular findings
were found in our study. Given the low rate of asymptomatic papilledema in this obese
population, further studies are needed to determine if previously published rates of
asymptomatic IIH and the association between obesity and IIH can be validated.
CR: D.G. Chu, None; W. Smith, None; C.M. Krispel, None; M.R. Ali, None; J.L.
Keltner, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4017-4020
Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204
415. Neuro-Ophthalmology Organizing Section: EY
4021 - A183
The Diagnostic Yield of Optic Nerve Ultrasonography for Differentiating
Papilledema From Pseudopapilledema in Eyes With Swollen Optic Discs
4022 - A184
Evaluation of Optic Nerve Head Drusen Using Spectral-domain OCT
(Spectralis)
M. Neudorfer, M. Siegman Ben-Chaim, C. Stolovitch, G. Dotan, A. Kesler. Department
of Ophthalmology, Tel-Aviv Medical Center, Tel Aviv, Israel.
L. Storm, R. Keshavamurthy, V. Brar, K.V. Chalam, S. Grover. Ophthalmology,
University of Florida, Jacksonville, FL.
Purpose: Swollen discs may be a sign of a life-threatening condition due to
increased intracranial hypertension (papilledema), or a sign of benign conditions
(pseudopapilledema) like optic nerve head drusen It is not uncommon to have
difficulty in differentiating between those conditions. The goal of this study was to
show that optic nerve ultrasonography is a reliable, accurate, readily available and
low-cost tool to differentiate papilledema from pseudopapilledema.
Methods: Forty-four patients with bilateral swollen discs were prospectively evaluated.
They all underwent comprehensive medical and ophthalmological examinations,
imaging (brain and orbit CT/MRI) and a lumbar puncture, as well as optic nerve
ultrasonography for detecting pathological widening of the nerve. We compared the
optic nerve ultrasonographic findings to the final diagnosis that had been reached after
the workup and follow-up, and calculated the sensitivity and specificity of optic nerve
ultrasonography for differentiating papilledema from pseudopapilledema.
Results: Twenty-three males and 21 females aged 12±6.5 y (2.5-30.5) participated. The
average follow up was 1.5 y. The calculated sensitivity of the examination was 95%,
with a specificity of 58%, a positive predictive value of 66%, a negative predictive
value of 93% and a correlation coefficient of +0.56 (p<0.001).
Conclusions: According to our results evaluation of optic nerve head by ultrasonography
had high sensitivity and specificity. Since this was a historic prospective study
and not a case-control study, it was possible to calculate the positive and negative
predictive values of the procedure for detecting papilledema. This information gives
a statistical basis for decision-making when determining the etiology of bilateral
swollen discs. According to our findings , optic nerve ultrasonography has significantly
higher sensitivity than funduscopy. As such, a combination of a thorough clinical
examination and optic nerve ultrasonography may be definitive and render further
workup unnecessary in some cases.
CR: M. Neudorfer, None; M. Siegman Ben-Chaim, None; C. Stolovitch, None; G.
Dotan, None; A. Kesler, None.
Support: None
Purpose: Optic nerve head drusen (ONHD) are white calcareous deposits, seen either
superficially on the optic nerve head or buried within it. Diagnosis of ONHD is made
by one or more ways: clinical exam, autofluorescence, ultrasound of the optic nerve, CT
scan and/or visual field examination. The present study describes features of ONHD
based on another diagnostic modality, the spectral-domain OCT (Spectralis).
Methods: This is an observational case series of 5 patients with bilateral ONHD with
a best-corrected visual acuity of 20/20 and no other posterior segment pathology.
All the patients underwent fundus photography, fundus autofluorescence, B-scan
ultrasonography, Spectralis OCT and Humphrey 30-2 threshold visual fields.
Results: All 5 patients had surface ONHD which were autofluorescent and echodense
on B-scan ultrasonography. Spectralis OCT findings in the corresponding areas include
‘scattered spots with high reflectivity’ casting a shadow underneath. The reflectivity
can be distinctly differentiated from the blood vessels on the optic nerve. Two thirds
of the patients had an arcuate scotoma on the Humphrey visual fields. No correlation
was found between the changes on Spectralis OCT with that of visual field.
Conclusions: Spectralis OCT is another useful ancillary investigation in the diagnosis
of ONHD and we describe the features in the present study.
CR: L. Storm, None; R. Keshavamurthy, None; V. Brar, None; K.V. Chalam, None; S.
Grover, None.
Support: Foundation Fighting Blindness, Inc., Owings Mills, Maryland.
4023 - A185
Increased Risk in Patients With Optic Disk Drusen for an Acute Non Arteritic
Anterior Ischemic Optic Neuropathy
4024 - A186
Assessment of Sleep Apnea in NAION Patients
M. Schargus, E. Gramer. Department of Ophthalmology, University Wuerzburg,
Wuerzburg, Germany.
Purpose: To evaluate: 1. the prevalence of NAION in patients with ODD 2. risk factors
compared to control groups.
Methods: 120 patients with uni- or bilateral ultrasonographic confirmed ODD were
prospectively, consecutively examined and standardized documented between 1987
and 2008. We evaluated whether there are any significant differences between three
patient groups: 1. 14 patients with ODD and NAION, 2. 106 patients with ODD without
NAION, 3. 420 patients from literature (1) with NAION without ODD in: age of
the patient at diagnosis, gender, vascular risk factors (hypertension, heart attack,
cardiopathy, hyperlipidemia), visual acuity (VA), mean stage of visual field loss (VFL)
and topography of VFL. Unpaired t-test was used for statistics.
Results: 1. 14 out of 120 patients with ODD presented at diagnosis an acute unilateral
NAION (10.3%).
2. Mean age at diagnosis: Patients with ODD and NAION were significantly younger
than patients with NAION without ODD (43,6±18,9 vs. 66,0±8,7 years)(p=0,06). Patients
with ODD without NAION were not significant younger than patients with ODD and
NAION (42,5±20,0 vs. 43,6±18,9 years) (p=0,8). Gender distribution showed a higher
prevalence of females in all three groups and no significant difference between the
three groups (females: 61,5% vs 61.3% vs 61,7%). Vascular risk factors were less frequent
in the group with ODD and NAION (36%) compared to patients with NAION without
ODD (57,9%). Visual acuity was significantly better in patients with ODD and NAION
which had in 79% a visual acuity better than 20/64 than patients with NAION without
ODD (35%). Patients with ODD without NAION had in 92,6% a VA better than 20/64.
Topography of VFL was similar in all patients with NAION with or without ODD
presenting most commonly VFL in the inferior hemifield (57% vs 46 %).
Conclusion: In patients with ODD acute NAION is more prevalent in a younger age
than in patients without ODD. In the group of 106 patients with ODD without NAION
we found that the higher the age of the patients the higher the frequency of superficially
visible ODD. Therefore we suggest that NAION may occur more often in eyes with
buried or less visible ODD than in eyes with superficially visible ODD. Further studies
are required. Every tenth referred patient with ODD showed an association with
NAION. Therefore ODD patients are at increased risk for NAION.
(1) Ischemic Optic Neuropathy Decompression Trial Study Group: Characteristics
of patients with NAION eligible for the Ischemic Optic Neuropathy Decompression
Trial, Arch Ophthalmol. 1996 Nov;114(11):1366-74.
CR: M. Schargus, None; E. Gramer, None.
Support: None
D.T. Nguyen1A, Y. Emoto2, H. Emoto3, M. Wang1A, T. Zavora4, A. Avakian1A, D.
Aggarwal1A, D.J. Levendowski4, J. Sebag5,1, A.A. Sadun1A. ANeuro-Ophthalmology, 1USC
Doheny Eye Institute, Los Angeles, CA; 2Department of Neuro-Ophthalmology,
Inouye Eye Hospital, Tokyo, Japan; 3Department of Ophthalmology, Tokyo Medical
and Dental University, Tokyo, Japan; 4Advanced Brain Monitoring, Inc., Carlsbad,
CA; 5VMR Institute, Huntington Beach, CA.
Purpose: To measure and compare parameters of obstructive sleep apnea (OSA) in
NAION patients and in controls (non-NAION) using in-home sleep studies.
Method: 9 NAION patients (7 males, 2 females, mean age 59) and 4 controls (4 females,
mean age 51) were recruited, given a history form and sleep log, instructed on the
usage of the Apnea Risk Evaluation System Unicorder (Advanced Brain Monitoring,
Inc, Carlsbad, CA), and sent home to acquire 2-3 nights of sleep study data. Each night,
the Unicorder provided continuous 7 hour recordings of oxyhemoglobin saturation
and pulse rate (reflectance pulse oximeter), snoring (microphone), head movement and
position (accelerometers), nasal airflow (nasal pressure transducer), and respiratory
effort by forehead venous pressure. Questionnaire and Unicorder data were masked
and submitted for automated analysis with quality control review. An apnea hypopnea
index with 4% desaturation (AHI-4%) and AHI with 1% desaturation (AHI-1%) were
calculated.
Results: Using AHI-4%, 4/9 NAION patients (44%) had AHI > 5 and 2/9 (22%) had AHI
> 15. Using AHI-1%, all NAION patients (100%) had AHI > 5, and 6/9 (67%) had AHI >
15. Of the non-NAION controls, three had AHI-4% < 5 and 1 had AHI-4% = 6. Applying
the AHI-1% criteria, three had AHI > 5, however none had AHI-1% > 15. Using either
the 4% desaturation or 1% desaturation criteria, the distribution of AHI values were
greater in the NAION patients as compared to the non-NAION controls.
Conclusions: The results support previous
reports of an increased prevalence of OSA in
NAION patients. The Unicorder may be used
in the home setting to measure parameters
of OSA in NAION patients.
CR: D.T. Nguyen, None; Y. Emoto, None; H.
Emoto, None; M. Wang, None; T. Zavora,
Advanced Brain Monitoring, Inc, E; A.
Avakian, None; D. Aggarwal, None; D.J.
Levendowski, Advanced Brain Monitoring,
Inc., I; J. Sebag, None; A.A. Sadun, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4021-4024
Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204
415. Neuro-Ophthalmology Organizing Section: EY
4025 - A187
Ethambutol Toxicity Presenting as Reversible Bitemporal Hemianopia in
Patients Being Treated for Mycobacterium Avium Complex
4026 - A188
Magnetic Resonance Imaging Distinguishes Optic Perineuritis From Typical
Optic Neuritis
T.A. Mendel1, D.A. Chesnutt2. 1University of Virginia, Charlottesville, VA;
2
Ophthalmology, University of North Carolina, Chapel Hill, NC.
A. Gupta1, M.J. Kupersmith1,2, D. Meltzer3. 1Ophthalmology, New York Eye and Ear
Infirmary, New York, NY; 2Institue for Neurology and Neurosurgery, Roosevelt
Hospital, New York, NY; 3Radiology, St. Luke’s/Roosevelt Hospital Center, New
York, NY.
Purpose: Reported visual toxicities from ethambutol are variable in presentation
and degree of reversibility.
Methods: Case series of patients with ethambutol visual toxicity.
Results: Four patients presented with a bitemporal hemianopia. The visual fields of one
patient are featured in the attached figures. Three of the four patients were followed
and the visual loss was reversible over approximately one year after discontinuation
of the ethambutol. The fourth patient is being followed. A fifth patient presented
with bilateral cecocentral defects and was referred back to the local ophthalmologist
for follow up.
Conclusions: In patients being treated with ethambutol for Mycobacterium avium
complex, reversible bitemporal hemianopia seems to be the most common presentation
of ethambutol toxicity. It is possible that infection with Mycobacterium avium complex
predisposes the optic chiasm rather than the optic nerves to uptake of ethambutol
and that the optic chiasm may be more resistant to permanent damage than the optic
nerves. Previous reports of severe permanent optic neuropathy in patients being
treated for Mycobacterium tuberculosis may be the result of synergistic damage to
the anterior visual pathways by the combination of ethambutol and infection with
Mycobacterium tuberculosis.
CR: T.A. Mendel, None; D.A. Chesnutt, None.
Support: None
4027 - A189
The Rate of Visual Loss From Stretch Optic Neuropathy
Purpose: The clinical presentations and features of several disorders that are due to
presumed inflammation of the optic nerve sheath (perineuritis) are similar to optic
neuritis, but perineuritis is not associated with development of MS and may require
systemic investigation. We hypothesized that MRI features can differentiate between
the two disorders.
Method: During the period from 2004-2008, we diagnosed 10 patients with optic
perineuritis and 170 patients with typical optic neuritis (18-50 yrs). We reviewed the
records for presenting symptoms (including pain on eye movement), clinical signs,
age, gender, visual acuity, mean deviation for 24-2 Humphrey (MD in db), and optic
disc features. We evaluated fat suppressed gadolinium enhanced T1-weighted and
short tau inversion recovery (STIR) orbital MRI in all patients for presence of abnormal
enhancement of the optic nerve or of the optic nerve sheath alone, and abnormal
signal in the optic nerve.
Results: For perineuritis patients, the average age was 34 yrs (range: 12-48 yrs); 9 were
females; at presentation 8 had visual acuity > 20/40; 5 had optic disc swelling; 9 had
pain on eye movement, and MD ranged from -1.3 to -31 db. Treatment with intravenous
methylprednisolone or high dose oral prednisone, followed by a gradual withdrawal,
normalized the visual acuity and visual field in 5/7 patients. The visual acuity, but not
the field, improved in 1; and 1 had progressive vision loss despite high dose steroid
therapy. In 3 patients without vision loss, pain resolved with oral nonsteroidal antiinflammatory agents. All perineuritis eyes (none unaffected eyes) showed abnormal
enhancement of the optic nerve sheath but not of the optic nerve. Abnormal optic
nerve signal on STIR occurred in 2. No perineuritis patients had abnormal signal
of brain white matter. No optic neuritis patients had abnormal enhancement of the
optic nerve sheath alone.
Conclusion: MRI performed in patients suspected of acute optic neuritis should
include orbital views with T1 fat suppression and gadolinium and STIR sequences
in order to differentiate perineuritis. This will allow proper counseling, workup and
treatment implementation.
CR: A. Gupta, None; M.J. Kupersmith, None; D. Meltzer, None.
Support: None
4028 - A190
Immunohistochemical Evaluation of S100A12 (Calgranulin C) in Alzheimer
Disease Optic Nerves
L.N. Johnson, C.R. Soni. Ophthal-Sch of Med, University of Missouri, Columbia,
MO.
Purpose: An important, though not well recognized, cause of thyroid related
optic neuropathy is stretch optic neuropathy. Of the few reported cases, none has
documented the rate of vision loss due to continuous stretching of the optic nerve.
Animal models have provided information on the tensile strength of the optic nerve,
but to our knowledge no in vivo studies of the tensile strength of the human optic
nerve have been reported. We present 3 cases of stretch optic neuropathy, one of which
provided a unique opportunity to quantify and estimate the rate of vision loss from
progressive stretching of the optic nerve.
Methods: Retrospective chart review of 3 cases of stretch optic neuropathy.
Results: All cases presented with blurry or spotty vision. Best corrected visual acuity
ranged from 20/20 to 20/40. Automated perimetry showed arcuate scotoma visual
field defects. The range of proptosis was 24 to 27 mm on Hertel exophthalmometry.
Ocular motility was normal. Two cases had dot hemorrhages in the fundus simulating
venous stasis retinopathy. Computed tomography showed thin extraocular muscles
and expanded orbital fat volume. Orbital decompression improved the visual
function. One case had progressive visual field loss over a 9-month period, providing
a unique opportunity to quantify and estimate the rate of vision loss from progressive
stretching of the optic nerve to complete blindness to be 775 days from onset of
visual symptoms.
Conclusions: Stretch optic neuropathy is an infrequent, but potentially reversible,
cause of visual loss and blindness from thyroid associated optic neuropathy.
CR: L.N. Johnson, None; C.R. Soni, None.
Support: Research to Prevent Blindness, Inc.
N.V. Hunter, D. Aggarwal, F.N. Ross- Cisneros, A.A. Sadun. Neuro-Ophthalmology,
USC/Doheny Eye Institute, Los Angeles, CA.
Purpose: S100A12 belongs to the S100 family of calcium-binding proteins. Of this S100
family, S100A2 which can be released by brain macrophages, microglia, and neutrophils
in microvasculature , and can act as a ligand to the receptor for advanced glycation
end products (RAGE). S100A12 has been shown to be involved with inflammation, the
initiation of amyloidosis, and high-molecular-weight insoluble protein aggregates,
in the brains of Alzheimer’s disease (AD) patients. Therefore, the aim of this study
was to investigate the presence of S100A12 (Calgranulin C) in AD optic nerves for its
possible role in optic neuropathy.
Methods: Optic nerve specimens were obtained at autopsy from twelve patients with
AD and compared to six normal age-matched control tissues. AD tissues were supplied
by our Alzheimer’s Disease Research Center (ADRC) and controls were purchased
through local eye banks. Tissues were immersion fixed in neutral buffered formalin,
dissected into cross-sectional profiles just proximal to the globe, then processed and
embedded into paraffin blocks. Sections were cut at 5 µm and immunostained, using an
indirect method with horseradish peroxidase and diaminobenzidine as the substratechromogen, with a mouse anti-human S100A12 monoclonal antibody at a dilution
of 1:50. Light microscopic images were viewed on a Zeiss Axioskop microscope and
captured by a digital camera and saved to a computer.
Results: Immunoreactivity for S100A12 in AD optic nerves appeared as circular plaquelike structures of various sizes often possessing an eccentrically placed large vacuole,
“punctate” staining in the cytoplasm of glial cells, and axonal elements. The brains
of the same patients demonstrated similar plaque-like structures staining positive
for S100A12. In contrast, age matched controls demonstrated very little staining for
S100A12 (Calgranulin C) protein in optic nerves and brains.
Conclusions: S100A12 was identified immunohistochemically in the optic nerves
of AD patients. The pattern of staining suggests that S100A12 is associated with a
plaque-like structure similar to lesions found in the brains of the same patients.
Thus, our findings suggest that S100A12 may play a role in activation of the RAGE
pathway toward inflammation, protein aggregate, and plaque formation associated
with AD optic neuropathy.
CR: N.V. Hunter, None; D. Aggarwal, None; F.N. Ross- Cisneros, None; A.A. Sadun,
None.
Support: Research to Prevent Blindness, Oakley Alzheimer’s Research Foundation,
NIH Grant EY03040
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4025-4028
Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204
415. Neuro-Ophthalmology Organizing Section: EY
4029 - A191
Anterior Ischemic Optic Neuropathy and Retinal Artery Occlusion: Check-Up
Interest During Hospitalization
4030 - A192
Ocular, Neurological and Endocrine Abnormalities in Children With Unilateral
Optic Nerve Hypoplasia
A. Feldman, P.-L. Cornut, M. De Bats, C. Burillon, P. Denis. Pavillon C - E Herriot
Hospital, Lyon, France.
L.L. Cooper, W.F. Astle, K.G. Romanchuk. Department of Surgery, University of
Calgary, Calgary, AB, Canada.
Purpose: To evaluate a standard check-up during hospitalization for patients presenting
anterior ischemic optic neuropathy (AION) or retinal artery occlusion (RAO).
Methods: It was a prospective study. The standard check-up was the following one:
ESR, CRP, CBC (on emergency), PT, aPTT, fibrinogen, antiphospholipid antibodies,
serum protein electrophoresis, homocysteinemia, fasting blood sugar, HbA1c,
cholesterol, triglycerides, ambulatory blood pressure monitoring, carotid doppler
ultrasound, echocardiography, ECG, cardiologic visit, brain MRI or CT, visual field,
fluorescein angiography and temporal artery biopsy at the slightest clinical sign of
giant cell arteritis.
Results: 46 patients were included. Mean age was 73 years (47-92). CRAO occured in 19
patients (41.3%), BRAO in 6 (13%) and AION in 21 (45.7%). Mean hospitalization duration
was 8 days (2-22). AION was bilateral in 2 cases. 6 patients had no atherosclerotic risk
factor. Risk factors were already balanced in 11 cases of 46 (23.9%). In 13 cases, a therapic
modification has been made to balance risk factors. Corticotherapy has been started in
8 cases (6 AION, 2 RAO); giant cell arteritis was proved in 2 cases (2 AION) and highly
suspected in 6 cases. In 8 cases (17.4%), the patient had to be transfered in another
specialized service while he was hospitalized (internal medicine, cardiovascular,
resuscitation). In 63% of the cases, standard check-up realized during hospitalization
led to a change of treatment. Underlying disease was potentially serious and needed
an urgent care in a great number of cases.
Conclusions: Standard check-up during hospitalization allowed in this study a rapid
multidisciplinary care adapted to RAO and AION. A therapeutic change has been
established in 2 cases out of 3 and almost 1 patient out of 5 has been transfered in a
specialized service.
CR: A. Feldman, None; P.-L. Cornut, None; M. De Bats, None; C. Burillon, None; P.
Denis, None.
Support: None
Purpose: Children with bilateral optic nerve hypoplasia usually present with bilateral
nystagmus and require investigation for neurological and endocrine abnormalities.
Fewer children present with unilateral optic nerve hypoplasia and less has been
reported on this disorder. The aim of this study is to examine the ocular features
as well as the neurological and endocrine abnormalities of children with unilateral
optic nerve hypoplasia.
Methods: A retrospective chart review was performed and data was obtained on
ocular, neurological and endocrine function
Results: Of the 9 patients (7 girls; 2 boys) with unilateral optic nerve hypoplasia, 5 had
right optic nerve hypoplasia and 4 had left optic nerve hypoplasia.Two patients had
bilateral nystagmus, 1 patient had nystagmus in the affected eye and the remainder
of the patients did not have nystagmus. Vision in the eye with optic nerve hypoplasia
varied from 20/40 to no light perception. Four patients attempted occlusion therapy
and improvement in vision was seen in 1 patient. Strabismus was present in 8 patients
(5 esotropia; 3 exotropia). Strabismus surgery was performed in 4 patients and all
patients had improvement in eye alignment. One patient had a metabolic abormality
in glucose management and 1 patient had neurological abnormalities.
Conclusions: Children with unilateral optic nerve hypoplasia have different ocular
presentation than children with bilateral optic nerve hypoplasia. Children with
unilateral optic nerve hypoplasia have a lower frequency of neurological and
endocrinological abnormalities. These finds may suggest a different mechanism
for the development of unilateral optic nerve hypoplasia than bilateral optic nerve
hypoplasia.
CR: L.L. Cooper, None; W.F. Astle, None; K.G. Romanchuk, None.
Support: None
4031 - A193
Perinatal Onset Static Encephalopathy: An Underrecognized Cause of Optic
Nerve Head Cupping in Children
4032 - A194
A Comparison of Multifocal ERG and Frequency Domain OCT Changes in
Patients With Abnormalities of the Outer Retina
S. kedar1A, D. Ghate1B, V. Vedanarayanan1C, N. Mungan1B, J.J. Corbett1A, C.J. Chen1B.
A
Neurology, BOphthalmology, CPediatric Neurology, 1University of Mississippi
Medical Center, Jackson, MS.
E.A. Dale1A, K.Y. Kay1A, J.G. Odel1B, V. Greenstein1B, D.C. Hood1C. APsychology,
B
Ophthalmology, CPsychology, Ophthalmology, 1Columbia University, New York,
NY.
Introduction: To evaluate optic nerve head (ONH) pallor and cupping in children with
perinatal onset static encephalopathy (POSE) and its association with age of onset,
type of cerebral palsy (CP), ambulation and neuro-radiologic abnormalities.
Methods: 42 consecutive children with POSE (without lasered retinas or intraocular
disease) were included. ONH was evaluated independently by 2 ophthalmologists by
dilated indirect ophthalmoscopy. A child’s ONH were labeled as large cup (cup/disc
ratio ≥ 0.5) and pale only if both observers agreed. ONH imaging was offered to all
children but was physically difficult for most. The pediatric neurologist (VV) determined
age of onset of POSE clinically and reviewed the available neuroimaging.
Results: 43% of the children with POSE had large cups and 33% had pallor. Large
cups were seen in 55% of children with neurologic insult (POSE onset) ≤ 28 weeks
of gestation (n=11) and 39% with onset > 28 weeks (n=31) (p=0.4). In children with
hemiplegic (n=11), diplegic (n=7), quadriplegic (n=21) and miscellaneous (n=3) CP, large
cups were found in 18%, 57%, 52% and 33% respectively (p=0.2) and ONH pallor in 9%,
14%, 52% and 33% respectively (p=0.06). In children who were ambulatory (n=24), and
non-ambulatory (n=18), large cups were found in 29% and 61% respectively (p=0.04)
and ONH pallor in 13% and 61% respectively (p=0.001). Brain CT/MRI was reviewed
in 20/42 children. All children with large cups and/or pallor had white matter changes
in the posterior periventricular region at the level of the atrium.
Conclusions: ONH cupping and pallor is common in POSE. ONH cupping and
pallor in POSE is not associated with age of onset as previously hypothesized, but is
associated with more severe forms of CP (diplegic and quadriplegic), more severe motor
disability (non-ambulatory status) and changes on neuroimaging in the posterior
periventricular region.
ONH changes in POSE may reflect global CNS pathology manifested by major motor
disability and seen as white matter changes on neuroimaging. Diagnosis of CP and
determination of the severity of disability is difficult in infancy; children with large
cups and/or disc pallor without glaucoma should be referred to pediatric neurologists
for evaluation and neuro-imaging.
CR: S. kedar, None; D. Ghate, None; V. Vedanarayanan, None; N. Mungan, None; J.J.
Corbett, None; C.J. Chen, None.
Support: None
Purpose: To compare the ability of the multifocal electroretinogram (mfERG) and frequencydomain optical coherence tomography (fdOCT) to detect retinal abnormalities.
Methods: Between Oct. 2007 and Nov. 2008, 61 patients (9 to 79 years of age) were referred
for mfERG and fdOCT testing to rule out or confirm a retinal etiology of visual loss. Patients
were evaluated with mfERG (103 scaled hexagons, VERIS, EDI) and fdOCT (optic disc circular,
macula 3D and horizontal line scans, 3DOCT-1000, Topcon). Amplitude and latency changes
of the mfERG responses, known to indicate outer retinal abnormalities, were analyzed. The
fdOCT scans were examined for changes in the outer retina (RPE, receptor and/or inner
nuclear layers). Local regions of abnormal mfERG or fdOCT were compared to local regions
of visual field sensitivity loss measured with static automated perimetry (24-2 Humphrey,
Zeiss). The mfERG results were categorized as: 1. Normal (normal amplitude and latency);
2. Abnormal (abnormal amplitude and latency consistent with the visual field defect); or
3. Inconclusive (subtle changes or local changes that did not topographically agree with
the visual field defect). The fdOCT results were categorized as: 1. Normal (normal outer
retina); 2. Abnormal (abnormal outer retina consistent with the visual field defect); or 3.
Inconclusive (see above).
Results: A total of 35 eyes (24 patients) were categorized as having an abnormal outer retina
based upon either the mfERG or fdOCT. Eighteen of these 35 eyes (13 patients) were abnormal
on both mfERG and fdOCT. Twelve eyes (8 patients) had an abnormal mfERG, but a normal
fdOCT scan. Five eyes (5 patients) had an abnormal fdOCT scan, but a normal (2 eyes/2
patients) or inconclusive (3 eyes/3 patients) mfERG. The group of 16 patients with abnormal
mfERG and normal fdOCT included cone-rod dystrophy, AZOOR, vascular damage, agerelated macular degeneration and acute idiopathic blind spot enlargement, while the group
of 5 patients with abnormal fdOCT and normal mfERG included local foveal problems (4
patients) and local vascular damage (1). Further, a retinal etiology could not be confirmed
in the remaining 37 patients due to normal mfERG and fdOCT results and/or results that
did not agree with visual field defects.
Conclusions: Although the mfERG and fdOCT results typically agree, some retinal
abnormalities are more easily detected in the mfERG, while others may be more apparent
on fdOCT. Examination of the cases in which there were clear mfERG changes, but subtle
fdOCT changes, improved our ability to detect abnormalities with fdOCT scans.
CR: E.A. Dale, None; K.Y. Kay, None; J.G. Odel, None; V. Greenstein, None; D.C. Hood,
Topcon, Inc, C.
Support: NIH Grant RO1-EY02115, NIH Grant R01-EY-09076
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4029-4032
Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204
415. Neuro-Ophthalmology Organizing Section: EY
4033 - A195
Comparison of Histologic Change in Lacrimal and Salivary Glands to 67GaCitrate Scintigraphy and T1 Gadolinium Enhanced MRI Findings in Sarcoid
Suspects
4034 - A196
Referrals for Suspicion of Optic Neuropathy: Analysis of Diagnostic Pitfalls
and Costs Incurred
B.J. Frankfort, N.R. Miller. Ophthalmology, Wilmer Eye Institute, Baltimore, MD.
H.J. Kim1A, D. Chu1A, L. Frohman1A, N. Mirani1B, R.E. Turbin1A. AOphthalmology,
B
Pathology, 1UMDNJ-New Jersey Med School, Newark, NJ.
Purpose: To correlate lacrimal gland (LGB) and oral (labial) minor salivary gland (SGB)
biopsy findings in patients who have gallium or gadolinium uptake of the lacrimal
glands (LG) and parotid glands (PG)performed to rule out sarcoid.
Methods: Retrospective chart review of consecutive patients (1/2003-11/2008)
undergoing LGB and SGB. Inclusion criteria: available preoperative 67Ga-citrate
scintigraphy (gallium) scan and/or MRI, and biopsy of LG and/or SG biopsy. Gallium
uptake (LG, PG) and MRI (LG, PG) size were each graded into 4 categories. Histology
was graded into 4 categories based on degree of inflammation, with the highest grade
being granulomatous inflammation.
Results: Forty-six patients (31 women, 15 men, average age 39) had both gallium and
MRI scans in 25 cases, gallium alone in 19, and MRI alone in 2. Gallium scans showed
increased LG uptake in 42, parotid uptake in 35, and submandibular uptake in 4. MRI
showed abnormal LG in 8 cases and abnormal parotid in 7 cases. Granulomatous
inflammation was seen in 11 cases (4 in both LG and SG, 5 in LG only, 2 in SG only).
8 granulomatous LGs had associated gallium scans that showed intense uptake in
4, moderate in 3, and mild uptake in 1. 12 of 13 patients with severe grade gallium
abnormality (LG or PG) had no higher than mild grade biopsy results (SGB or LGB),
and 1 had moderate grade inflammation (SGB or LGB). MRI findings in granulomatous
LGs were moderate in 1 case, mild in 2, and normal in 1. Granulomatous inflammation
in SG had intense PG gallium uptake in 3, moderate uptake in 1 and mild in 1, and
had severe abnormalities on MRI in 1, and normal MRI in 2.
Conclusions: 67Ga-citrate scintigraphy (gallium) scan and MRI are sensitive in
identifying inflammatory reaction but less specific for identifying granulomatous
change in LG and in SG. Surgeons may consider SG biopsy in conjunction with LG
biopsy as SG may have diagnostic value even when the imaging and LG biopsy are
unremarkable. Ultimately, sarcoidosis is a clinical diagnosis and LG and SG biopsies
remain a useful confirmatory test.
CR: H.J. Kim, None; D. Chu, None; L. Frohman, None; N. Mirani, None; R.E.
Turbin, None.
Support: Research to Prevent Blindness, Inc, NY; Lions Eye Research Foundation
of NJ
Purpose: a. Identify ophthalmologic conditions commonly misdiagnosed as an optic
neuropathy and the confusing clinical features that may lead to incorrect suspicion.
b. Characterize the extent of the clinical workup typically performed for these
patients.
c. Quantify the financial costs of evaluation for optic neuropathy.
Methods: Large consecutive case series, single examiner.
Results: Optic Neuropathy is a potentially devastating disorder that may occur in isolation
or as a manifestation of a systemic disease. When a diagnosis of optic neuropathy is made
or suspicion is considerable, prompt neuro-ophthalmologic evaluation is often warranted.
However, the diagnosis of optic neuropathy can be complex, which may lead to referral
even in situations where the diagnosis of optic neuropathy is suspect. As the workup for
optic neuropathy can be extensive, referral for optic neuropathy often is accompanied
by a significant financial burden. Furthermore, the implications of neurologic ocular
involvement can be emotionally devastating to a patient. Therefore, it is in our best
interest to ensure that referral for optic neuropathy occurs primarily in settings of the
highest suspicion. To achieve this, diagnoses commonly mistaken for optic neuropathy
should be identified. We have performed a retrospective analysis of 102 consecutive
patients seen by a single neuro-ophthalmologist at the Wilmer Eye Institute from 20022008 who were referred for suspicion of optic neuropathy but did not, in fact, have the
disease. Patients had an average age of 60.8 (SD = 15.9), were mostly female (71%), and
were predominantly Caucasian (87%). Referral sources included general ophthalmologists,
ophthalmic subspecialists, optometrists, internists, neurologists and neurosurgeons.
Visual acuity, presence of a relative afferent pupillary defect, color vision, and optic
nerve findings were highly variable. The vast majority of patients (>80%) had undergone
prior visual field testing, and most patients had undergone prior neuroimaging (MRI or
CT). Anterior segment pathology (including refractive error) and retinal pathology each
accounted for 28% of referrals. Glaucoma accounted for an additional 18% of referrals.
Surprisingly, 21% of patients had a normal eye examination. Incurred diagnostic costs
were substantial.
Conclusions: Common ophthalmic diseases are frequently mistaken for an optic
neuropathy. Such diagnostic errors by the referring physician suggest either a lack
of understanding of the characteristics of an optic neuropathy or a concern that the
physician is “missing something” and may lead to both unnecessary emotional burden
for the patient and a significant cost to the health care system.
CR: B.J. Frankfort, None; N.R. Miller, None.
Support: None
4035 - A197
Clinical Polymorphism of Myasthenia Gravis Beginning With Isolated Ocular
Symptoms
4036 - A198
NMR-Based Metabolomic Analysis of Cerebrospinal Fluid and Serum in
Neuro-Ophthalmological and Neurological Diseases - A Diagnostic Tool?
J. Boumendil1, C. Vignal-Clermont2, J. Allali1, J.-L. Dufier1, S. Morax2. 1Necker, paris,
France; 2Rothschild’s ophthalmologic foundation, paris, France.
A.J. Sinclair1A,1B, M.R. Viant1C, G.R. Wallace1A, A.K. Ball1D, M.A. Burdon1A, E.A. Walker1B,
P.M. Stewart1B, S.P. Young1E, S. Rauz1A. AAcademic Unit of Ophthalmology, School of
Immunity, Infection and Inflammation, BEndocrinology, School of Experimental
Medicine, CSchool of Biosciences, DNeurology, School of Experimental Medicine,
E
Rheumatology, School of Immunity, Infection and Inflammation, 1University of
Birmingham, Birmingham, United Kingdom.
Purpose: the aim of this study is to highlight the clinical diversity of myasthenia
gravis beginning with isolated ocular symptoms.
Methods: we present a 15 patients series that we have been taking care of at
Rothschild’s Ophthalmologic Foundation from 2002 to 2007. Every patients have
been examinated by the same ophthalmologist for isolated ocular symptoms. An
acetylcholin-receptor antibodies research, a cerebral RMI and a chest tomography
have been systematically realized.
Results: When the disease was diagnosed, 11 patients out of 15 had a ptosis with a
diplopia, 2 had an isolated ptosis and 2 had an isolated diplopia. After investigations,
we discovered that three patients had a malignant thymoma and one had a thymic
hyperplasia. An autoimmune disease association has been found with 2 patients: the
first one had a Hashimoto’s thyroiditis and the second one has developed an optical
neuro-myelitis few years after his myasthenia gravis. Only three patients secondarily
developed a generalized myasthenia gravis. This could be explained by the early
attending of these patients, and the common prescription of an immunosuppressive
therapy reducing the risk of secondarily generalised myasthenia gravis according
to some studies.
Conclusions: Despite the small number of patients, this study well underlines the
clinical polymorphism of ocular myasthenia gravis, the risks it may cause, and
the important role of the ophthalmologists in the diagnosis of this disease. Close
collaboration between ophthalmologists and neurologists is needed to ensure a well
taking care of these patients.
CR: J. Boumendil, None; C. Vignal-Clermont, None; J. Allali, None; J.-L. Dufier,
None; S. Morax, None.
Support: None
Purpose: Establishing biomarkers for conditions affecting the central nervous system
have to date proven to be problematic. Processes such as gene transcription, and
environmental factors, can affect the metabolic fingerprint of tissues. The recent
innovation of metabolomic analysis of biofluids has the capacity to integrate
these bio-influences into a single biomarker profile. We therefore sought to define
whether metabolomic biomarker profiling of cerebrospinal fluid (CSF) and serum
could potentially distinguish between idiopathic intracranial hypertension (IIH),
multiple sclerosis (MS) and cerebrovascular disease (CVD) from patients with mixed
neurological diseases.
Methods: Spectra of CSF (n=87) and serum (n=72) were acquired using 1H NMR
spectroscopy. Multivariate pattern recognition analysis was used to identify disease
specific metabolite biomarker profiles. The metabolite profiles were then used to predict
the diagnosis of a prospectively collected cohort of patients (n=25).
Results: CSF metabolite profiles were able to predict diagnosis with a sensitivity and
specificity of 80% for both IIH and for MS. The CVD serum metabolite profile was
75% sensitive and specific. On analysing the second prospective patient cohort, the
established metabolite biomarker profiles generated from the first cohort showed
moderate ability to segregate patients with IIH and MS (sensitivity: specificity of
63%:75% and 67%:75%, respectively).
Conclusions: These findings suggest that NMR spectroscopic metabolic profiling of
CSF and serum can identify differences between IIH, MS, CVD and mixed neurological
diseases. Metabolomics may, therefore, have the potential to be developed into a
clinically useful diagnostic tool. The identification of disease-unique metabolites
may also impart information on disease pathology.
CR: A.J. Sinclair, None; M.R. Viant, None; G.R. Wallace, None; A.K. Ball, None; M.A.
Burdon, None; E.A. Walker, None; P.M. Stewart, None; S.P. Young, None; S. Rauz,
None.
Support: Alex Sinclair is a Medical Research Council Clinical Research Training Fellow
(UK) and the Academic Unit of Ophthalmology is supported by the Birmingham Eye
Foundation (Registered (UK) Charity 257549)
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4033-4036
Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204
415. Neuro-Ophthalmology Organizing Section: EY
4037 - A199
Dry Eye, Blinking, and Hemifacial Spasm
4038 - A200
Inter-Observer Variability of Hertel Exophthalmometry Stratified by Training
Experience
I.S. Kassem1, C. Evinger2, H. Pomeranz1. 1Department of Ophthalmology, North
Shore-Long Island Jewish, Great Neck, NY; 2Department of Neurobiology and
Behavior, Stony Brook University, Stony Brook, NY.
B.A. Karwoski, F.A. Killian, C. Rosenberg, Y.P. Glavas. Ophthalmology, New York
University, New York, NY.
Purpose: Hemifacial spasm (HFS) is a disorder characterized by involuntary facial
muscle spasms that begin in one eyelid and progress to the ipsilateral lower facial
muscles. Eyelid spasms result from closely spaced bursts of orbicularis oculi (OO)
muscle activity that resemble blink oscillations with an extremely short interblink
interval. The primary cause of HFS is unilateral pulsatile arterial compression of
the facial nerve at the root entry zone. This pressure causes facial nerve weakness,
resulting in poor tear film production that initiates an adaptive increase in the blink
reflex. We investigated the effect of increased cornea afferent activity on the eyeblink
and the incidence of eye irritation in HFS patients.
Methods: To investigate the effect of reduced tear production, four male spraguedawley rats had surgical implantation SO nerve stimulation electrodes and OO
electromyogram (EMG) recording electrodes. Rats were tested for several days prior
to surgical removal of the exorbital lacrimal gland. We reduced cornea afferent
activity in two dry eye model rats by anesthetizing the cornea with tetracaine. We
also recorded OOEMG activity of two normal human subjects and increased cornea
afferent activity using a simultaneous air puff and reflex blink stimulus. To investigate
if eye irritation is more prevalent in HFS patients, we performed a retrospective chart
review of 36 HFS patients and compared the incidence of their eye complaints with
age-matched controls.
Results: Lacrimal gland removal in rats resulted in blink oscillations accompanying
innocuous reflex blink stimuli without any change in reflex blink threshold, blink
amplitude, or trigeminal excitability. Reducing cornea afferent activity in these rats
with corneal anesthetic reduced the probability of oscillations evoked by reflex blinks.
In normal human subjects, increasing cornea afferent activity by pairing the reflex
stimulus with an air puff increased the probability of blink oscillations. HFS patients
also had more complaints of eye irritation compared to control patients.
Conclusions: Cornea irritation initiates the production of multiple blinks to a normally
single blink-evoking cutaneous trigeminal stimulus. These blink oscillations may
occur because of coincident cutaneous and elevated cornea afferent activity. The
spasms of lid closure in HFS might be an exaggeration of these multiple blinks closely
spaced together in time. Together, these studies show that eyelid spasm disorders
such as HFS may be due in part to a disruption in the adaptation to cornea drying
and irritation.
CR: I.S. Kassem, None; C. Evinger, None; H. Pomeranz, None.
Support: EY07391 (CE) and NS4467301 (IK).
Purpose: To investigate the inter-observer variability and accuracy of Hertel
exophthalmometry and analyze whether it is a learned clinical skill improved through
repetition and experience.
Methods: In this comparative study, simultaneous bilateral Hertel exophthalmometry was
performed on four different patients in consecutive fashion by 36 ophthalmologists stratified
by training level experience (residents, oculoplastics fellows, and neuro-ophthalmology and
oculoplastics attendings). The patients had no history of orbital disease and were of different
genders and ethnic backgrounds. Each observer was blinded and three measurements were
taken for each patient using a Marco Prism Exophthalmometer (Marco Instrument Co,
Jacksonville, Florida, USA). Additionally, each resident completed a brief survey evaluating
their formal education and exposure to exophthalmometry.
Results: The PGY-2 residents demonstrated the greatest variation for globe position and
intercanthal distance, respectively (PGY-2: 6mm and 20mm; PGY-3: 5mm and 13mm; PGY-4:
3.5mm and 8mm). The subspecialty attendings (gold standard) showed the least variation
for globe position at 2mm. There was no statistical difference for accuracy of measurements
for globe position between each level of training (ANOVA analysis p = 0.336). The difference
in accuracy for intercanthal distance between the PGY-2 residents and all other groups was
statistically significant (PGY-3: p = 0.032; PGY-4: p = 0.008; Attg: p = 0.011). The difference in
accuracies for intercanthal distance between PGY-3 and PGY-4 and each with the attendings
were not statistically significant. Finally, 59% of residents had formal clinical training, 6%
had didactic training and 76% felt it was a useful clinical skill.
Conclusion: The inter-observer variability for axial globe positioning and intercanthal
distance is inversely correlated with training experience. The accuracy for globe positioning
in exophthalmometry did not correlate with training level. However, the accuracy for
intercanthal distance did correlate with training level. It appears that more senior residents
improve the placement of the exophthalmometer footplates over the temporal margin of the
lateral orbital rim. Secondly, the survey showed that almost half the residents felt they did
not have adequate clinical training on how to perform exophthalmometry but support its
clinical utility. In summary, evaluating the anteroposterior position of the globe within the
orbit is not a learned skill but is felt to be clinically relevant and valuable. New emphasis on
exophthalmometry training may be warranted to improve our evaluation and management
of orbital disease.
CR: B.A. Karwoski, None; F.A. Killian, None; C. Rosenberg, None; Y.P. Glavas, None.
Support: None
4039 - A201
Prognosis and Riskprofile of Patients With Aniridia
4040 - A202
Choroidal Effusion: An Important Hallmark in Carotid-cavernous Fistula.
Report on 2 Cases
E. Gramer1, C. Reiter1, G. Gramer2. 1Department of Ophthalmology, University
Wuerzburg, Wuerzburg, Germany; 2Hospital for Pediatric and Adolescent
Medicine, University Heidelberg, Heidelberg, Germany.
M.G. Todorova, A.M. Palmowski-Wolfe, J. Messerli, P. Meyer. Ophthalmology,
University of Basel Eye Clinic, Basel, Switzerland.
Aniridia is a panocular eye malformation caused by heterozygous mutations within
PAX6 gene, a paired-box transcription factor, or cytogenetic deletions of chromosome
11p13 that encompass PAX6. PAX6 has a wide expression in the developing eye, in
the neuroectoderm and the surface ectoderm and therefore in their derivates, lens,
cornea and retina.
Purpose: To evaluate in patients with aniridia: 1)Frequency of congenital cataract,
lens dislocation, nystagmus, corneal opacification, poor foveal development, family
history of aniridia. 2)Frequency of glaucoma (GL) or ocular hypertension (OH) and
maximum intraocular pressure (IOP max). 3)Visual acuity prognosis.
Methods: Retrospective analysis of ophthalmologic, paediatric and internal findings in
30 consecutively examined patients with aniridia and photo documentation. Age of the
patient at first clinical examination, family history and IOP max were requested.
Results: 1)Mean age at first clinical examination in 30 patients with bilateral aniridia
(17 male, 13 female)was 28±19,3 years (range 2 month-62 years). Age distribution at
first clinical examination: up to 9 years: 23,3%, 10-19: 13,3%, 20-29: 13,3%, 30-39: 10%,
40-49: 26,7%, 50-59: 3,3%, 60-69: 6,7%. Congenital cataract had 76,7% (23 of 30 patients),
in 20 patients bilateral, in 3 unilateral. 5 patients (16,7%) had bilateral dislocation of
the crystalline lens upwards. 8 had corneal opacifications, 3 unilateral, 5 bilateral.
One patient had poor foveal development, one patient (3,3%) had a Wilms´ Tumor. 2
patients (6,7%)had optic nerve hypoplasia. 53,3% presented nystagmus. Family history
of aniridia was found in 10 patients (33,3%) with 1-4 relatives. 2) Frequency of glaucoma
was 66,7% (20 patients), 10% unilateral, 90% bilateral. Mean IOP max of 20 glaucoma
patients was 35,9 mmHg in the right and 32,6 mmHg in the left eye. 3)A decreased
visual acuity in the better eye of 20/100 or less was found in 60% of all patients.
Conclusions: Inspite of pseudophakia patients with aniridia had severely decreased
visual acuity related to nystagmus, glaucomatous damage and as a result of the other
associated various ocular abnormalities. Elevated IOP occurs very infrequently in
childhood. Buphthalmus was only found in one patient. Most commonly IOP starts
to increase not before adolescence. Schlemm´s canal may be absent in many patients.
Due to a highly variable expression of aniridia in relatives a thorough examination
of family members is required to provide early diagnosis, amblyopia prophylaxis
and a correct genetic counceiling.
CR: E. Gramer, None; C. Reiter, None; G. Gramer, None.
Support: None
Purpose: Indirect fistulas are usually low-flow fistulas with a reduced arterial blood
flow. Retrograde venous drainage through the cavernous sinus into to the superior
ophthalmic vein (SOV) is less pronounced than in high-flow fistulas. As a consequence,
there is less bruit on auscultation, which makes the diagnosis difficult. Associated
findings such as choroidal effusion, which may lead to a shallow anterior chamber
and an elevated IOP, are considered to be rare complications.
Methods: We report on two patients, where the ultrasound biomicroscopic (UBM)
demonstration of choroidal effusion was paramount in diagnosing an indirect carotidcavernous fistula (CCF). The patients underwent ophthalmological examination
including a 50 Hz UBM (Paradigm Medical Industries, Inc, P60TM) to examine the
choroidea, the anterior chamber depth and the anterior chamber angle.
Results: The 1st patient, a 56-year-old man, presented with chemosis, episcleral
injection and proptosis of the right eye (4mm). A diagnostic MRI had been read
as consistant with SOV thrombosis, EOP or pseudotumor orbitae. A follow up
examination revealed a new shallow anterior chamber OD with a normal IOP of
17mmHg. UBM confirmed the reduced anterior chamber depth of 2.5mm (norm:
2.7mm) and demonstrated annular cilio-choroidal effusion with edema of the ciliary
body. An angle closure was suggested by an anterior chamber angle of <20° in all four
quadrants, namely 13.8° @12h, 12.2° @3h, 12.7° @6h, 19.3° @9h. This effusion lead to
the suspected diagnosis of an indirect CFF which could be confirmed on MRA.The
2nd patient, a 62-year-old man, presented with episcleral injection and proptosis of
the right eye (3.5mm). Doppler sonography showed a prominent SOV. Neuroimaging
revealed an indirect CCF from an AV-malformation in the cavernous sinus. A followup one week after therapeutic embolisation of the fistula revealed a shallow anterior
chamber OD, IOP: 21mm. UBM confirmed worsening of the clinical situation with
a chamber depth of 1.86 mm, a closed chamber angle of 7.33° @3h, 7.17° @9h, 0 @12h
& 6h, secondary to annular cilio-choroidal effusion, which lead to a pseudo-plateau
configuration of the iris.
Conclusions: Angle-closure secondary to annular cilio-choroidal effusion was found
in both patients with indirect CCFs. UBS seems to be an useful non-invasive diagnostic
tool to aid in diagnosis and follow-up of patients with indirect CCF. We suggest, that
more widespread use of UBM might reveal choroidal effusion in more patients with
low flow fistulas and thus help in early diagnosis of this disorder.
CR: M.G. Todorova, None; A.M. Palmowski-Wolfe, None; J. Messerli, None; P.
Meyer, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4037-4040
Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204
415. Neuro-Ophthalmology Organizing Section: EY
4041 - A203
Dizziness: Simple Clinical Test Battery To Evaluate Hyperstimulation
Syndromes
J. Ilson1, K.J. Ciuffreda2. 1Ophthalmology, E S Harkness Eye Institute, New York, NY;
2
Vision Sciences, SUNY College of Optometry, New York, NY.
Purpose: It is well known that some individuals without apparent neurological disease
are hypersensitive to motion, especially in the peripheral visual fields. Furthermore,
many patients with head trauma, stroke, and even migraine exhibit a similar but
more exaggerated heightened response. We sought to develop simple, inexpensive
procedures to reproduce these phenomena in a clinical setting
Methods: We examined 20 symptomatic patients/subjects and 15 asymptomatic
subjects using a rapidly moving OKN drum, repeated convergence to near-point,
proprioceptive neck vibration, with a total test time of less than five minutes.
Results: All previously symptomatic subjects experienced their stereotypic
hypersensitivity to all of the above whereas asymptomatic controls did not exhibit a
similar response. The stereotypic hypersensitivity response included disorientation,
panic, nausea, a variety of visual phenomena (diplopia, visual tilt, visual avoidance of
complex patterns), dizziness and/or gait ataxia sometimes lasting several hours.
Conclusion: Using this simple test battery with patients, we were able to reproduce
consistently their real-life symptoms. This even applies to those with unremarkable
neurological, ophthalmological, and vestibular examinations and in some cases with
normal neuro-imaging. Our findings may have diagnostic and therapeutic as well as
medical-legal ramifications.
CR: J. Ilson, None; K.J. Ciuffreda, None.
Support: None
4042 - A204
Migrainous Visual Aura Due to Focal Cerebral Lesions. Can the Diagnosis
Be Made on the Semiology of Attacks? Nine Case Reports and Review of the
Literature
P.N. Shams1,2, G.T. Plant1,2. 1Ophthalmology, Moorfields Eye Hospital, London,
United Kingdom; 2Neuro-ophthalmology, The National Hospital for Neurology
and Neurosurgery, London, United Kingdom.
Purpose: To identify clinical features which could differentiate between the visual
auras of idiopathic migraine and those due to structural cortical lesions which also
fulfill the diagnostic criteria for idiopathic migraine with visual aura, as defined by
The International Classification of Headache Disorders.
Methods: Prospective observational study including nine cases of migraine-like visual
aura due to focal cerebral lesions seen in the practice of one neuro-ophthalmologist at
Moorfields Eye Hospital and The National Hospital for Neurology and Neurosurgery
London between 1986 and 2008. A further 31 cases from the literature were identified
by searches of PubMed from 1966 until March 2008.
Results: Five key clinical features are outlined in detail to help to identify which
patients with migraine-like visual auras require further investigation; 1) Onset
of visual aura for the first time in fourth or fifth decade of life; 2) Duration of the
visual aura less than 5 minutes; 3) Increase in frequency or change in the pattern
of longstanding visual auras; 4) Visual auras recurring in the same location in the
visual field; 5) Unexplained visual field defect (VFD) and/or persistent VFD following
a typical visual aura.
Conclusions: Photopsia and the slow propagation of scintillating scotoma across the
visual field are strongly associated with the visual aura of idiopathic migraine. Our
cases support the observation that visual auras fulfilling the diagnostic criteria for
idiopathic migraine, can arise from acquired cortical lesions. Despite the considerable
overlap in the characteristics of visual aura caused by migraine, epilepsy and structural
cerebral lesions, certain features can help to differentiate between these conditions
in order to identify patients who require further investigation. We hypothesize
that the co-morbidity and overlap in clinical features of these chronic neurological
disorders is due to a common underlying pathophysiology; namely a state of neuronal
hyperexcitability. Whether due to genetic predisposition or acquired through brain
injury, neuronal hyperexcitability increases an individuals’ susceptibility to the
generation of cortical spreading depression, the electrophysiological correlate of the
visual aura in migraine.
CR: P.N. Shams, None; G.T. Plant, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4041-4042
Wednesday, May 6, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 4696 - 4712 / D962 - D978
460. Amblyopia I Organizing Section: EY
4696 - D962
Post-Operative Grating Acuity Outcomes in Children With Down Syndrome
and Bilateral Cataracts
4697 - D963
How Does One Define Success in Amblyopia Treatment?
G.E. Quinn1, B.M. Melia2, Pediatric Eye Disease Investigator Group. 1Pediatric
Ophthalmology, Childrens Hospital of Philadelphia, Philadelphia, PA; 2Jaeb Center
for Health Research Foundation, Tampa, FL.
S.R. Salomao, A. Berezovsky, P.Y. Sacai, J.M. Pereira, N.N. Cavascan, M.B. Tartarella.
Dept of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil.
Purpose: Down syndrome is the most commonly identified genetic form of
developmental disability with an estimated incidence of 1:600 live births in Brazil.
Cataract occurs in 1.5-20% of Down syndrome cases, mainly bilaterally, leading to
severe visual impairment if not treated. The purpose of this study is to investigate
grating acuity outcomes in children with Down Syndrome undergoing cataract
extraction.
Methods: Best-corrected grating acuity (BCGA) was measured electrophysiologically
by sweep visual evoked potential (sweep-VEP) technique from each eye in 13 patients
with Down Syndrome (age 6 months - 10 years; 6 females) who had been operated
for bilateral cataracts (11 aphakic - 22 eyes, 2 pseudophakic - 3 eyes). An additional
group of 10 patients with Down Syndrome and absence of cataract in each eye was
also tested (age 2 months - 12 yrs; 3 females). Acuity deficits from mean normal were
calculated based on age norms from our own lab. Amblyopia was diagnosed when
interocular acuity difference > 0.1 logMAR was detected.
Results: Age at surgery ranged from 1.5 to 60 months of age (mean=13.4±12.9; median=9).
BCGA was measured within 3 months - 8 years after surgery (mean=24.3±33.6 mos.;
median=7.2 mos). In cataract-operated patients, BCGA deficits were present in all
eyes (0.13 - 1.36 logMAR; mean=0.61±0.31; median=0.50), with amblyopia in 7 (53.8%)
patients. Patients with Down Syndrome without cataract showed BCGA deficit in
13(65.0%) eyes (0.08 - 0.79 logMAR; mean=0.37±0.25; median=0.27) and none had
amblyopia. Greater acuity deficits were found in cataract-operated eyes compared
with eyes from patients with Down Syndrome and no cataract (Mann-Whitney rank
sum test, P=0.023).
Conclusions: Post-operative grating acuity outcomes in Down syndrome patients
with bilateral cataracts disclosed substantial deficits as well as high frequency of
amblyopia. Better acuity outcomes could probably be achieved with earlier diagnosis
and surgical treatment, providing improved visual function and quality of life for
these patients.
CR: S.R. Salomao, None; A. Berezovsky, None; P.Y. Sacai, None; J.M. Pereira,
None; N.N. Cavascan, None; M.B. Tartarella, None.
Support: None
Purpose: To compare definitions used to determine outcome in studies of amblyopia
treatment
Methods: Using data from completed amblyopia clinical trials conducted by the
Pediatric Eye Disease Investigator Group to develop a statistical model, we simulated
visual acuity data for clinical trials of treatment for moderate amblyopia over a range
of ages and treatment effects and compared type I and II error rates for 8 different
definitions of treatment success that have been used or proposed as outcome measures
for treatment studies of amblyopia.
Results: Of the continuous outcome measures considered (lines improved, proportion
of deficit corrected (PDC), and intraocular difference (IOD)), lines improved had
good statistical properties across the range of scenarios studied. Both PDC and IOD
had high chance of type I error when the treatment could adversely affect sound eye
acuity. Of the dichotomous outcomes considered (better than 20/25, better than 20/32,
improved 2 or more lines, equal vision in both eyes, and better than 20/32 or improved
3 or more lines), improved 2 or more lines generally had the best statistical power.
Like PDC and IOD, the equal visual acuity outcome had high type I error when the
treatment could adversely affect sound eye visual acuity. In general, given a fixed
sample size, continuous outcomes had greater power to detect treatment differences
than the dichotomous outcomes.
Conclusions: Choice of an outcome should be based on biological plausibility, clinical
relevance, and safety, as well as statistical properties that maximize the chances of
detecting a treatment difference and minimize chances of coming to an erroneous
conclusion. Either continuous or dichotomous outcome measures may be reasonable
choices for a primary outcome measure for clinical trials of amblyopia treatment. The
outcomes of lines improved and improvement of 2 or more lines of visual acuity had
good statistical properties across a wide range of conditions likely to be encountered
in studies of amblyopia treatment, although other choices of outcome may perform
well under specific circumstances. IOD and equal visual acuity had poor statistical
properties in most circumstances and should not generally be used as primary
outcome measures.
CR: G.E. Quinn, None; B.M. Melia, None.
Support: National Eye Institute EY011751
4698 - D964
Macular Thickness and Retinal Nerve Fiber Layer Thickness Measurements in
Amblyopic and Normal Eyes of Children Using Spectral Domain OCT
4699 - D965
Macular Thickness in Amblyopic Eyes With Myopic Anisometropia
P.H. Kok1A, Y.C. Besselink1B, R. De Kinkelder1C,2, J. Kalkman1C, M.E.J. Van Velthoven1A,
F.D. Verbraak1A. AOphthalmology, BOrthoptics, CBiomedical Engineering and
Physics, 1Academic Med Ctr Amsterdam, Amsterdam, Netherlands; 2Topcon
Europe Medical BV, Capelle a/d IJssel, Netherlands.
Purpose: The purpose of this study was to investigate the macular thickness and
retinal nerve fiber layer (RNFL) thickness, in relation to the axial length (AL) in
amblyopic and normal eyes of children, using spectral domain OCT (SD-OCT).
Methods: Included amblyopic and healthy children underwent full ophthalmic and
orthoptic examination, volume scanning of the macula and optic disc with SD-OCT
(32 b-scans consisting of 512 a-scans, 3D OCT-1000,Topcon) and recording of AL using
the IOL master (Zeiss Meditec). The foveal and pericentral retinal thicknesses (RT)
and peripapillary RNFL thickness were then calculated using a custom built Matlab
(The MathWorks, Inc.) based program.
Results: Twenty-four amblyopic patients (14 boys
and 10 girls, mean age 7.7 ± 1.9) and 25 healthy
children (11 boys and 14 girls, mean age 8.1 ± 1.5)
were enrolled in this study. Except for four
amblyopic children, a negative correlation was
found between the AL and RT (r=0.44 p<.05).
After excluding these four patients, in the
remaining group of 20 children both the
amblyopic and fellow eyes were significant
shorter and had thicker pericentral RT compared to control eyes (see Table). No
differences were found in the other parameters between the three groups. AL was a
significant covariate (p<.01), whereas age and gender were not. After correcting for
AL, no significant differences were found between the three groups for all parameters.
Using paired testing amblyopic eyes were 0.3 ± 0.4 mm shorter than their fellow eyes,
however they did not have significantly different RT and RNFL thickness
measurements.
Conclusions: In 20 amblyopic children in our study, the thicker pericentral RT as
compared to healthy controls seems to be explained by the shorter AL. However,
in four amblyopic children an inverse correlation between AL and RT was found.
Further research will focus on this finding.
CR: P.H. Kok, None; Y.C. Besselink, None; R. De Kinkelder, Topcon Europe Medical
BV, E; J. Kalkman, None; M.E.J. Van Velthoven, None; F.D. Verbraak, None.
Support: None
Y. Pang, G. Goodfellow, C. Allison, S. Block, K.A. Frantz. Illinois Coll of Optom,
Chicago, IL.
Purpose: To compare macular thickness of the sound eye to that of the amblyopic eye
using optical coherence tomography (OCT) in patients with myopic anisometropia.
The associations between macular thickness, axial length and refractive error in the
amblyopic eyes were also investigated.
Methods: 24 subjects (17 females and 7 males) with a mean age of 10.6 yrs (5 to 25 yrs)
were recruited. Macular thickness, A-scan, visual acuity, and cycloplegic refraction
were measured on the amblyopic and sound eye. Macular thickness of both eyes
was compared (paired t-test). Partial correlations were used to test the relationships
among macular thickness, axial length and refractive error in amblyopic eyes while
controlling for age and sex.
Results: Mean ± SD spherical equivalent in
amblyopic eyes was -11.33 ± 3.16 diopters (D)
with a range of -5.25 to -17.50 D and -2.10 ±
3.12 D in sound eyes. The mean magnitude
of anisometropia was 9.23 ± 3.71 D, ranging
from 3.63 to 17.50 D. Mean axial length was
26.87 ± 1.68 mm in amblyopic eyes and 23.46
± 1.40 mm in sound eyes. Macular thickness
is shown in Table 1. A significant difference
in macular thickness was found between
amblyopic and sound eyes. No correlation was found between macular thickness and
axial length or macular thickness and refractive error in amblyopic eyes.
Conclusions: Histopathological studies have shown retinal thinning with myopia.
Retinal involvement in amblyopia is controversial with some studies reporting a
thicker macula in the amblyopic eye. We believe this is the first study to measure
macular thickness in amblyopic eyes associated with myopia. Amblyopic eyes with
high myopia had significantly thicker minimum and average foveas but thinner inner
and outer maculae compared to sound eyes. Macular thickness in the amblyopic eyes
was not related to axial length or refractive error.
CR: Y. Pang, None; G. Goodfellow, None; C. Allison, None; S. Block, None; K.A.
Frantz, None.
Support: Illinois Society for the Prevention of Blindness, CIBA Vision, and Illinois
College of Optometry Faculty Research Fund
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4696-4699
Wednesday, May 6, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 4696 - 4712 / D962 - D978
460. Amblyopia I Organizing Section: EY
4700 - D966
The Pupil in Suppression and Amblyopia
E.P. Herlihy1, S.M. Archer2. 1Pediatric Ophthalmology, Seattle Children’s Hospital,
Seattle, WA; 2Pediatric Ophthalmology, University of Michigan Kellogg Eye Center,
Ann Arbor, MI.
4701 - D967
The Prevalence of Amblyopia and it Relationship With the Child’s Diagnosis
and Age: The Iowa KidSight Vision Screening Experience
A. Leon, S.Q. Longmuir, R.J. Olson, W. Pfeifer, B. Zimmerman, W.E. Scott. Dept of
Ophthalmology, University of Iowa, Iowa City, IA.
Purpose: To test the hypothesis that the apparent afferent pupillary defect that has
been reported in amblyopic eyes is due to lack of fixation by the eye with poorer
vision, and to determine if there is a magnitude of pupillary asymmetry that cannot
be attributed to lack of fixation in amblyopia.
Methods: Ten volunteers with equal best corrected visual acuity in each eye and a
normal eye exam were recruited. A twenty prism diopter base down prism was placed
over the right eye, and the subject was instructed to fixate on a distant target and
suppress the displaced image. Pupillary reactions were assessed with the swinging
flashlight test. Asymmetric responses were quantified using neutral density filters.
Results: Asymmetric pupillary responses were observed in seven of the ten subjects
(70%) with equal visual acuity and normal eye exams when the subjects were instructed
to maintain fixation with the eye without the prism [video clip]. Pupillary reactions
equalized with a 0.3 log unit neutral density filter held over the eye without the prism
in six of the seven subjects (86%). The pupillary asymmetry reversed in one of the
seven subjects (14%) with the 0.3 log unit filter.
Conclusions: Lack of fixation caused an apparent afferent papillary defect in seven of
ten normal subjects without amblyopia. Thus, there is no need to postulate a failure of
development of retinal ganglion cells in amblyopes. However, no pupillary asymmetry
resulting from lack of fixation measured greater than 0.3 log units in our study. Any
larger asymmetric response warrants further investigation for optic nerve disease.
CR: E.P. Herlihy, None; S.M. Archer, None.
Support: None
Purpose: Vision screening programs allow early detection of children with or at risk
for amblyopia. We analyzed the effect of child’s diagnosis and age on the prevalence
of amblyopia in children screened by Iowa KidSight Vision Screening Program.
Methods: Database from Iowa KidSight Vision Screening Program was used to
identify children referred to an eye specialist. The diagnosis from eye specialist,
presence of amblyopia, and child’s age were recorded and analyzed with logistic
regression analysis.
Results: From May 1, 2000 to April 30, 2007, 2680 children were referred for an eye
specialist evaluation. Follow-up information was available for 1981 children. Of
these, 731 children were found to have amblyopia. After performing our statistical
analysis we found significant interaction between diagnosis and age (p=0.02). We
analyzed the effect of age on all diagnosis types and found only statistically significant
increase of prevalence in amblyopia in the children with anisometropia (p=0.002)
with increased age.
Conclusions: Among the different diagnosis groups, anisometropia was the only
diagnosis group in which the prevalence of amblyopia increased significantly with
age. Vision screening technologies have allowed earlier detection of this condition.
Strategies for early treatment for anisometropic children could lead to prevention or
early treatment of amblyopia. Continued efforts in early detection of this condition
could lead to better outcomes.
CR: A. Leon, None; S.Q. Longmuir, None; R.J. Olson, None; W. Pfeifer, None; B.
Zimmerman, None; W.E. Scott, None.
Support: RPB, Lions Clubs of Iowa, Lions Club International Foundation
4702 - D968
Naso-Temporal Asymmetry of Retinal Function in Children With Strabismic
Amblyopia
4703 - D969
Experience-Dependent Plasticity of Form and Motion Mechanisms in Human
Amblyopia
F. Campagna1, B. Falsini2, G. Carnovale Scalzo1, V. Scorcia1, G. Scorcia1, C. Russo1, M.
Rechichi1, A. Paola1, G. Scorcia1, D. Bruzzichessi1. 1Ophthalmology, Magna Graecia
University, Catanzaro, Italy; 2Institut of Ophthalmology, Catholic University,
Rome, Italy.
S.I. Chen1,2, A. Chandna 3, M.W. Pettet4, A.M. Norcia4. 1Ophthalmology, The Galway
Clinic, Galway, Ireland; 2Ophthalmology, University of Liverpool, Liverpool,
United Kingdom; 3Ophthalmology, The Royal Liverpool Children’s Hospital,
Liverpool, United Kingdom; 4Infant Vision Lab, The Smith-Kettlewell Eye Research
Institute, San Francisco, CA.
Purpose: Previous studies¹ have shown naso-temporal asymmetry of spatial
interaction in strabismic amblyopia. The aim of this study was to compare nasotemporal hemiretinal function with pattern electroretinogram (PERG) in children
with strabismic amblyopia.
Methods: Ten children with a diagnosis of strabismic amblyopia (3 males, 7 females,
mean age: 6 ± 1 years), with a visual acuity of 0.4-0.7 in the amblyopic and of 1.0 Snellen
units in the fellow eye were analyzed. All patients had convergent strabismus ≥ 10
prismatic dioptres (D). All children were hyperopic and four were astigmatic > 1.5
D. Pattern electroretinogram (PERG) was recorded in response to transient stimuli
generated on a 19” TV monitor (temporal frequency 2 Hz, check size 30’), presented
to the central retinal region (22 x 22 degrees) and to nasal and temporal hemiretinal
fields. Analysis was according to ISCEV guidelines.
Results: In the amblyopic eyes, the central PERG was significantly reduced in
mean amplitude (p < 0.01) compared to the fellow eyes. However, nasal hemiretinal
amplitude losses were significantly greater than corresponding temporal losses ( - 23.2
± 4 % versus - 4.5 ± 5.6 %, p < 0.01).
Conclusions: Strabismic amblyopia shows a retinal dysfunction characterized by
a naso-temporal asymmetry, suggesting a retinal genesis of the reduction of nasal
hemiretinal input to the visual cortex.
CR: F. Campagna, None; B. Falsini, None; G. Carnovale Scalzo, None; V. Scorcia,
None; G. Scorcia, None; C. Russo, None; M. Rechichi, None; A. Paola, None; G.
Scorcia, None; D. Bruzzichessi, None.
Support: None
Purpose: Deprivation of patterned visual input during early visual development
leads to both anatomical and functional losses in the deprived eye. Disagreement
exists (human literature) as to whether the non-deprived eye shows super-normal
behavior. Here we use spectral analysis of Visual Evoked Potential (VEP) responses
to isolate relative position and motion/transient responses in previously untreated
children who experienced deprivation of high-spatial frequency input in one eye due
to chronic optical defocus (anisometropia).
Methods: Normal children (n=16) and previously untreated amblyopes (n=12) under
eight years old were studied longitudinally during clinical treatment. VEP responses to
a 3.76Hz Vernier displacement stimulus were subjected to spectral analysis. Positional
responses (first harmonic) and motion/transient responses (second harmonic) were
the main outcome measures compared before and after occlusion therapy.
Results: Position-specific responses are super-normal in the non-deprived eye
and markedly subnormal in the deprived eye prior to treatment. Motion/transient
responses, on the other hand show no difference from normal in the non-deprived
eye and milder losses in the deprived eye. After occlusion of the initially deprived
eye, the position signal decreased in the initially non-deprived eye and increased in
the initially deprived eye. No measurable effect of occlusion occurred for the motion/
transient response.
Conclusions: These results suggest that position and motion/transient signals arise
from separate mechanisms with very different sensitivity to optical deprivation and
conversely, to reversal of the deprivation effect by occlusion therapy.
CR: S.I. Chen, None; A. Chandna, None; M.W. Pettet, None; A.M. Norcia, None.
Support: EY06579, OR2001-99a. CT: If Other, enter the registry site and corresponding
number
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4700-4703
Wednesday, May 6, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 4696 - 4712 / D962 - D978
460. Amblyopia I Organizing Section: EY
4704 - D970
Comparison of the Accommodative Response in Amblyopic and NonAmblyopic Eyes
4705 - D971
The Role of Autorefraction in Addition to Visual Acuity Testing,
Questionnaires and Inspection in Preschool Vision Screening at 3.5 Years in
Japan
C. Rook1, D. Oystreck1, S.E. Loudon2, D.G. Hunter1. 1Ophthalmology, Children’s
Hospital, Boston, MA; 2Ophthalmology, Erasmus University, Rotterdam,
Netherlands.
Purpose: Accommodative dysfunction has previously been reported in amblyopic
eyes. Most studies were performed in a non-clinical setting, using few subjects and
no children. In this study, a prospective, case control design was used to assess the
accommodative ability of amblyopic children.
Methods: Two clinical tests of accommodation were used to compare the amblyopic
eye with the sound eye and in age matched controls: 1) WAM 5500 binocular
accommodation autorefractor, and 2) dynamic retinoscopy. The accommodative
response to a 3 diopter stimulus was assessed under binocular and monocular viewing
conditions.
Results: To date, 37 amblyopic and 24 control subjects (mean age 7.8 years) have been
tested. Accommodative response was normal in 49% of amblyopic eyes, 70% of sound
eyes, and 76% of non-amblyopic control eyes under binocular viewing conditions.
Accommodative response was normal in 51% of amblyopic eyes, 62% of sound eyes,
and 70% of non-amblyopic control eyes under monocular viewing conditions. Dynamic
retinoscopy was normal in 84% of amblyopic eyes, 92% of sound eyes, and 100% of
non-amblyopic control eyes.
Conclusions: When tested with an objective, quantitative method, amblyopic eyes
appeared to have a reduced accommodative response under both binocular and
monocular viewing conditions. Sound eyes in amblyopia patients performed as
well as non-amblyopic eyes in controls. The reduced accommodative response in
amblyopic eyes may have implications in the treatment of amblyopia as well as in
amblyopia screening. Enrollment of more patients and controls will be needed to
provide sufficient power for meaningful statistical analysis.
CR: C. Rook, None; D. Oystreck, None; S.E. Loudon, None; D.G. Hunter, None.
Support: Research to Prevent Blindness Walt and Lilly Disney Award
4706 - D972
Benefits of Electrodiagnostic Testing (EDT) in the Assessment of Amblyopia in
Children With Congenital Ptosis and Its Correlation With Orthoptic Findings
Y.H. Luo1A,2, A. Liasis2,3, B. Walters2, Y.A. Abou-Rayyah2,1B. AOphthalmology, BAdnexal
Service, 1Moorfields Eye Hospital, London, United Kingdom; 2Clinical and
Academic Department of Ophthalmology, Great Ormond Street Hospital, London,
United Kingdom; 3The Ulverscroft Vision Research Group, Institute of Child
Health, London, United Kingdom.
Purpose: To determine the benefit of EDT in the management of congenital ptosis
in children
Methods: A retrospective comparative case series of 33 patients with congenital ptosis
who attended a tertiary paediatric oculoplastics centre. Patients with other ocular /
neurological conditions which compromised vision were excluded. As part of their
investigations patients underwent both electrodiagnostic (EDT) and orthopitc testing.
The results were compared to look for similarities and discrepancies on patient cooperation with each assessment modality, the outcomes of the assessments, and the
management decisions based on the assessments.
Results: In 41 out of 70 episodes (59%), both EDT and orthoptic were in agreement
to the presence or absence of amblyopia and as a result management decision was
based on both assessments. In a number of cases only either EDT or orthoptic testing
could be achieved and as a result management was based on the successful modality
(3 separate episodes each for EDT and orthopitic testing). Of interest the EDT and
orthoptic findings were in disagreement in 23 patient episodes.
In these cases management was based on orthoptic findings in 18 episodes while on
EDT findings in the remaining 5 episodes.
Conclusions: EDT was found to be beneficial in attaining monocular visual assessment
in all the children patients. It did not alter clinical management in children able to
carry out subjective recognition acuity tasks or in those older than 15 months of age,
as subjective recognition acuity testing is considered the gold standard for monocular
visual assessment on which management is based.
In situations when EDT and orthoptic findings contradict each other, other clinical
factors (e.g. extent of ptosis, compliance of occlusion therapy) should be taken into
consideration in the decision making. In older patients who are able to perform
subjective recognition visual acuity, orthoptic assessments alone may be adequate in
monitoring their visual function. We recommend to perform both EDT and orthoptic
assessments in patients under 15 months of age, to maximise the detection of amblyopia
and allow early institution of appropriate treatment.
CR: Y.H. Luo, None; A. Liasis, None; B. Walters, None; Y.A. Abou-Rayyah, None.
Support: None
C. Matsuo1, T. Matsuo2, K. Kio3, N. Ichiba 3, H. Matsuoka 3. 1Orthodontist, Kyoyama
Dental Center, Okayama City, Japan; 2Ophthalmology, Okayama University
Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama
City, Japan; 3Okayama City Government Health Care Office, Okayama City, Japan.
Purpose: Children at 3.5 years in Japan undergo physical, mental and developmental checkup,
based on Maternal and Childhood Health Law since 1961. Vision and hearing examinations
were included since 1991. The vision-screening program consists of 3 steps: questionnaires
and home visual acuity testing as 1st step, visual acuity testing by nurses and inspection
by medical officers at regional Health Care Centers as 2nd step, and detailed examinations
by ophthalmologists as 3rd step. In this study, we conducted hand-held autorefraction in
addition to visual acuity testing and inspection at regional Heath Care Center to reveal
whether autorefraction leads to better detection of eye problems.
Methods: Hand-held autorefraction was done by a single well-trained examiner (C.M.) in
265 children at 3.5 years who visited at Okayama East Health Care Center in 6 consecutive
sessions from Nov 2007 to Feb 2008. As the current standard, eyes were inspected by medical
officers, and visual acuity tests using 0.1 and 0.5 Landolt-C cards at 5 m for each eye were done
by nurses in children who failed or did not undergo visual acuity testing at home. Children
were sent to 3rd step examinations by ophthalmologists, based on refractive error criteria: >3
diopters myopia, >2 diopters astigmatism, or >1 diopter hyperopia in either eye, in addition
to the current criteria: 1) failure in either eye for 0.5 visual acuity, 2) eye-related symptoms
raised by questionnaires, or 3) eye problems detected by medical officers.
Results: Notice to visit ophthalmologists was issued for 64 children (24%), and 37 of those
(58%) did so to make documents wiith final diagnoses sent back to Health Care Office. Of
the 64 children, 12 was sent to ophthalmologists based on the current criteria only, 9 based
on both the current criteria and the refractive error criteria, and 43 based on the refractive
error criteria only. Eleven of 12 children visiting ophthalmologists by the current criteria
had diagnoses such as amblyopia and strabismus. In contrast, 16 of 25 children visiting
ophthalmologists by the refractive error criteria only had mainly diagnoses of refractive
errors with no serious problems.
Conclusions: Autorefraction in addition to visual acuity testing and inspection led to
additional eye disease detection at 3.5 years. Autorefraction is not recommended as an
additional test from the viewpoint of cost-effectiveness as far as the current system was
conducted appropriately.
CR: C. Matsuo, None; T. Matsuo, None; K. Kio, None; N. Ichiba, None; H. Matsuoka,
None.
Support: Special Budget Allocation for Community-Oriented Research from Okayama
University in 2007
4707 - D973
Neural Correlates of Pattern Perception in Human Amblyopia: An MEG Study
Z.A. Hirji1A, F. Cortese1A, H.C. Goltz1A, D.O. Cheyne1B, A.M. Wong1A. AOphthalmology
and Vision Sciences, BDiagnostic Imaging, 1The Hospital for Sick Children, Toronto,
ON, Canada.
Purpose: The neural basis of amblyopia remains elusive: there is contradictory
evidence on whether visual deficits result primarily from dysfunction of early visual
cortex (V1/V2) or extrastriate cortex. In this study, we investigated the roles of early
and late visual cortical areas and their interactions in human amblyopes by using
magnetoencephalography (MEG).
Methods: Prior to MEG recording, 2 adult amblyopes and 6 visually normal subjects
performed a behavioural experiment in which subjects detected static Glass patterns
(radial or rotational) monocularly. The signal strength (% of correlated dot-pairs) of
the Glass patterns was varied to determine the level at which the subject perceived
the pattern 80% of the time. During MEG recording, the signal strength of the Glass
pattern was set at the previously measured 80% performance level so that the amblyopic
and fellow eyes in patients with amblyopia and healthy eyes in normal controls were
stimulated equally across subjects and stimulus conditions.
Results: Behaviorally, Glass pattern perception by the amblyopic eyes produced slower
response times and required higher signal strengths when compared to the fellow and
healthy eyes. Using beamformer-based spatial filtering, brain activity maps revealed
bilateral activation in early visual areas (V1/V2) shortly after visual presentation for
both amblyopic and normal subjects. However, ~250 ms after visual presentation,
stimulation of the amblyopic eye produced attenuated activity in the extrastriate
lateral occipital complex (LOC) bilaterally, and different activity in the right inferior
parietal area, when compared to the fellow and healthy eyes. In addition, time course
analysis of the source waveforms at these brain locations revealed a different pattern
of interaction between early and later visual areas when stimulating the amblyopic
eye, than was observed for fellow and healthy eyes.
Conclusions: The neural basis of amblyopia may be related to an abnormal interaction
between early visual (V1/V2) and extrastriate cortices.
CR: Z.A. Hirji, None; F. Cortese, None; H.C. Goltz, None; D.O. Cheyne, None; A.M.
Wong, None.
Support: Canadian Foundation for Innovation, Canadian National Institute for the
Blind
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4704-4707
Wednesday, May 6, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 4696 - 4712 / D962 - D978
460. Amblyopia I Organizing Section: EY
4708 - D974
Patten Visual Evoked Potential (P-VEP) in Adult Monocular Amblyopia
4709 - D975
EPSC Changes After CSPG Degradation in Rat Visual Cortex During Visual
Critical Period
S.-K. Moon, K. Lim. Department of Ophthalmology, School of Medicine, Ewha
Womans University, Mok-dong Hospital, Seoul, Republic of Korea.
Z.Q. Yin, C. Wang. Southwest Eye Hospital, Southwest Hospital, Chongqing, China.
Purpose: To investigate the clinical guideline of pattern visual evoked potential
(P-VEP) parameters as the diagnostic criteria for adult monocular amblyopia
Methods: From Jan 2000 to May 2008, medical charts of patients who visited for medical
certificates for the military service were reviewed. Any suspicious malingering patients
or bilateral amblyopic patients were excluded. Only patients who has definite causes
of amblyopia or whose amblyopia has been confirmed on the childhood medical
record were included in the study group. Normal subjects who have best-corrected
visual acuity more than 20/20 were selected as the control group. The P100 latency
and amplitude were compared between the amblyopic eye and the normal control
group. The P100 latency and amplitude ratios were calculated from both eyes and were
compared between the amblyopic group and the normal control group.
Results: Eighty-two charts of patients were reviewed. Sixty-seven patients were
included in this study. Forty-seven patients were monocular amblyopic group and
20 patients were normal control group. Of the 47 monocular amblyopic patients, 32
had anisometropic amblyopia, 4 had strabismic, 3 had visual deprivation, and 8 had
idopathic amblyopia. The P100 latency of monocular amblyopic eye was 118.69±27.02msec,
which was significantly delayed than that of normal subjects, 103.62±5.45msec. The
P100 amplitude of monocular amblyopic eye was 5.89±3.23μV, which was significantly
decreased than that of normal subjects, 8.84±4.57μV. The P100 latency ratio of monocular
amblyopic group was 1.18±0.32, which was significantly higher than that of normal
subjects, 1.03±0.02. The P100 amplitude ratio of monocular amblyopic group was
0.65±0.36, which was significantly lower than that of normal subjects, 0.77±0.15. All
patients with P100 latency ratio more than 1.10 had monocular amblyopia. All patients
with P100 amplitude ratio less than 0.47 had monocular amblyopia. 21(44.7%) out of 47
monocular amblyopic patients showed P100 latency ratio within 2 SD of the normal
control group. 30(63.8%) out of 47 monocular amblyopic patients showed P100 amplitude
ratio within 2 SD of the normal control group.
Conclusions: The P100 latency ratio more than 1.10 or the P100 amplitude ratio less than
0.47 can be used as the diagnostic criteria of adult monocular amblyopia. Although
some patients with monocular amblyopia showed normal P-VEP parameters, P-VEP
could be employed usefully as a diagnostic tool for adult monocular amblyopia. The
clinical correlation is mandatory to diagnose adult monocular amblyopia.
CR: S.-K. Moon, None; K. Lim, None.
Support: None
Purpose: For the treatment of amblyopia is closely related with critical period of visual
plasticity which terminative mechanism was unknown. The relationship between
chondroitin sulphate proteoglycan (CSPG) and synaptic events during the critical
period of the visual cortex was studied. CSPG, an extracellular matrix component
condenses around neurons to form perineuronal nets (PNNs) encapsulating the cell,
and may be a mechanism that ends the critical period of visual plasticity.
Methods: Recordings from normal rat (Long Evens) visual cortex between postnatal
week 3 (P3W) to P8W were compared with those from rats after chondroitinase ABC
(chABC) injections to degrade CSPG. Whole-cell patch-clamping was used to record
glutamatergic excitatory postsynaptic currents (Glu-EPSCs), and NMDA and AMPA
receptor mediated EPSCs from layers II - IV in tissue slices of the visual cortex.
Results: 1: EPSCs were recorded from 33/58 neurons in the normal visual cortex. There
were no significant changes in NMDA-EPSCs amplitude (pA) (P > 0.05) between P3W
to P8W. AMPA-EPSC amplitude steadily increased between P3W and P7W (P6W-P8W
vs P3W, P < 0.05) coinciding with the closure of the rat’s visual critical period. NMDA/
Glu EPSC amplitude ratios gradually decreased between P3w - P6W, concomitant with
an increase in AMPA/Glu EPSC amplitude ratios. 2: Neurons (31/51) were isolated
and recorded after CSPG degradation following chABC injections 7 days before
recording. There was a significant and steady increase in NMDA-EPSC amplitudes
until P7W (P < 0.05 vs P3W). AMPA-EPSCs amplitudes similarly increased, albeit not
as significantly. After chABC NMDA/Glu EPSC amplitude ratios were consistently
higher than in normal animals, whereas the AMPA/Glu EPSC amplitude ratios were
consistently lower.
Conclusions: The PNNs formed with CSPG appear to be correlated with a decrease
in of NMDA-EPSC amplitudes in rat visual cortex between P4W - P8W. CSPG may
preferentially inhibit of NMDA transmission and synaptic plasticity as development
proceeds by shifting the balance towards more AMPA/Glu receptor sites, thus, ending
the visual critical period.
CR: Z.Q. Yin, None; C. Wang, None.
Support: Chinese NSFC grant # 30672280
4710 - D976
Effect of a Combined Patching and Atropine Treatment in Patients With
Anisometropic Amblyopia With Microtropia for the Prevention of Amblyopia
Recurrence
4711 - D977
How Dutch Orthoptists Handle Non-Compliance With Occlusion Therapy for
Amblyopia
F. Matsumoto1, A. Yamabe1, H. Yamamoto1, Y. Nakao1, A. Wakayama2, Y. Shimomura2.
1
Ophthalmology, Kinki Univ Sch of Medicine,Sakai-Hospital, Sakai, Japan;
2
Ophthalmology, Kinki Univ Sch of Medicine, Osaka-sayama, Japan.
Purpose: We have previously reported that anisomertopic amblyopia with microtropia
often recurs after a patching treatment. To prevent the recurrence, we investigated
the effect of a combined patching and atropine occlusion treatment in patients with
anisometropic amblyopia with microtropia.
Methods: Eight patients (mean age, 69±10 months) with anisometropic amblyopia
with microtropia were included. The mean refractive errors for the amblyopic and
fellow eyes were +5.69±1.11D and +2.15±1.5D (spherical), respectively. Patient’s pretreatment visual acuity (VA) of the amblyopic eye ranged from 0.30-1.04 logMAR. The
treatment protocol was as follows: (1) an initial patching time of eight hours or longer
per day was set, (2) the patching time was reduced to 3-5 hours per day depending to
the patient’s age when the VA ceiling of the amblyopic eye was reached, (3) if VA of
the amblyopic eye remained stable, treatment of 1% atropine eye drops once per day
was started on the fellow eye. During a follow-up period of 6-72 months, recurrence
of amblyopia was determined based on the VA stability of the amblyopic eye.
Results: Seven (87.5%) of the eight patients, had improved VA of 0 logMAR in the
amblyopic eye after the patching treatment and were able to maintain their VA after
the atropine occlusion treatment. The other patient (12.5%) had improved VA of 0.15
logMAR after the patching treatment and the VA was further improved after the
atropine occlusion treatment. The overall treatment required 8-17 months; and the
respective means were 5.14 months for the patching treatment of 8 hours or longer
per day, 2 months for the patching treatment of 3-5 hours per day, and 3.14 months
for the atropine occlusion treatment. None of the patients experienced amblyopia
recurrence during the follow-up period.
Conclusions: Because atropine occlusion promotes binocular rivalry under binocular
condition, an atropine occlusion treatment following patching can effectively prevent
recurrence of amblyopia.
CR: F. Matsumoto, None; A. Yamabe, None; H. Yamamoto, None; Y. Nakao, None; A.
Wakayama, None; Y. Shimomura, None.
Support: None
A.M. Tjiam1A, E. Vukovic1A, W.L. Asjes-Tydeman1B, M.M. Sinoo2, S.E. Loudon1A, H.J.
Simonsz1A, J.R. Polling1A. AOphthalmology, BPublic Health, 1Erasmus Medical Center,
Rotterdam, Netherlands; 2Orthoptics, Utrecht University, Utrecht, Netherlands.
Purpose Non-compliance causes treatment failure in occlusion therapy for amblyopia.
Predictors of low compliance are low initial visual acuity, a low parental fluency in Dutch,
a low level of education, and country of origin (IOVS 2006; 47: 4393-400). We examined
how Dutch orthoptists handle non-compliance with occlusion therapy in general and
sought for differences related to the risk factors.
Methods A structured questionnaire was sent to all Dutch orthoptists. Nine orthoptists
in low-SES areas (group A) and 23 orthoptists dispersed over the Netherlands (group B)
were studied in more detail with a semi-structured interview, structured questionnaires
and direct, non-participated observations. Patients’ demographic characteristics,
organizational structure of the clinic, attendance-rates, concept of non-compliance,
awareness of non-compliance, attitude towards non-compliance, approach towards
non-compliance and communication with parent and child were evaluated. In children
living in low-SES areas compliance was measured electronically.
Results Mean age of patients of B-orthoptists was 4.2 ± 1.1 years and A-orthoptists 4.6 ±
1.2 years. Patients of B-orthoptists had less than moderate fluency in Dutch in 4.6% and
A-orthoptists in 36.9%. Patients of A-orthoptists were Dutch in 33.9%, Surinamese in 7.5%,
Moroccan in 21.8% and Turkish in 13.2%. The electronic measurements of the compliance
showed that approx. 48% of the children occluded less than 50% of the prescribed
occlusion time; 16.7% did not occlude at all. One-hundred-and-seventy-four of all Dutch
orthoptists (58%), who answered the structured questionnaire, estimated their patients’
compliance to be 72.7%, on average. The A and B-orthoptists estimated their patient’
compliance to be 66% and 75.5%, respectively. Patients of A-orthoptists did not show up at
appointments in 9.6% and B-orthoptists in 6%. None of the B-orthoptists and four of the nine
A-orthoptists found themselves inadequate in dealing with non-compliance. A-orthoptists
gave 2’30” explanation about diagnosis and treatment to parents and B-orthoptists 4’21”.
All orthoptists did not communicate with the child during their explanation.
Conclusion Orthoptists underestimated the size of poor compliance with occlusion
therapy. Despite differences in fluency in Dutch, explanation of A-orthoptists is shorter,
which is caused by a shorter allotted time for a patients’ first visit (21’ versus 27’24”).
CR: A.M. Tjiam, None; E. Vukovic, None; W.L. Asjes-Tydeman, None; M.M. Sinoo,
None; S.E. Loudon, None; H.J. Simonsz, None; J.R. Polling, None.
Support: ZonMw The Netherlands organisation for health research and development
#6320.0008 CT: www.trialregister.nl/trialreg/index.asp
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4708-4711
Wednesday, May 6, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 4696 - 4712 / D962 - D978
460. Amblyopia I Organizing Section: EY
4712 - D978
Can Orthoptically Trained Personnel Carry Out Preschool Screening in the
Absence of an Orthoptist?
L. North, M.F.P. Griffiths, G. Menon. Frimley Park Hospital Foundation Trust,
Frimley, United Kingdom.
Purpose: To determine the number of false positive and false negative referrals made
to a Hospital Eye Service from a Community Vision Screening service carried out by
Health Visitors
Methods: A retrospective cross sectional study was carried out from January 2000- January
2002. Data was obtained from patient records of 126 children referred to the Princess
Mary’s Hospital, MOD Cyprus, who were booked to see either the Ophthalmologist &/or
the Orthoptist. Health visitors under went training in 2001 with the visiting orthoptist in
order to carry out a pre-school visual screening service. Standards of testing and referral
guidelines were issued for them to follow and further data was collected to determine the
number and % of children referred that were true and false positives, source of referral,
age of the child at referral, time lapse between referral and ophthalmic appointment,
reason for referral, whether standards of testing were followed. A convenience sample
was then taken from the children that had been previously tested by the health visitor
during 2001 and re tested by the orthoptist to determine the number of false negative
results. Factors that were also examined included, method of assessment, assessment
outcome, general logistics for examination, equipment used and age of child at testing.
Results: Prior to the introduction of the new direct referral system to the ophthalmic
service at The Princess Mary’s Hospital, MOD, Cyprus 41% were false positive. This shows
a high percentage of the total referrals made were unnecesssary.Following the training
of health visitors in pre-school visual assessment, 54% of the direct referrals made by the
health visitor proved to be false positive. In spite of this high false postive referral rate,
8 out of 34 children that had been classified as normal were found to be false negative
on retest by the orthoptist. 4 children were found to have bilateral reduced vision, 2 had
manifest squints, 1 child was found to have a significant esophoria and a further child
failed the 20 dioptre prism test. All required referral to the ophthalmologist.
Conclusions: This study provides considerable support to the recommendations that
orthoptists should carry out pre-school visual screening services.Despite training and a
higher false positive referral rate, the number of false negatives is a concern and could be
indicative of an even higher number prior to training.The effectiveness of orthoptists in
the detection of visual defects remains to be the most acceptable method of assessment
of pre-school children but further evaluation needs to carried out in order to provide a
service when there is not a permanent orthoptist. Is some screening better than none?
CR: L. North, None; M.F.P. Griffiths, None; G. Menon, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4712
Wednesday, May 6, 3:45 PM - 5:30 PM Palm A Paper Session Program Number Range: 4749 - 4755
463. Amblyopia II Organizing Section: EY
4749 - 3:45PM
Amblyopia in Children with Cranial Nerve Palsies Secondary to Brain Tumors
M.E. Hoehn1A, M.L. Bratton1B, N.C. Kerr1A. AOphthalmology, BCollege of Medicine,
1
Univ of Tennessee Health Sci Ctr, Memphis, TN.
Purpose: Early onset visual pathology tends to be more amblyogenic. We evaluated the
relationship between age of onset for cranial nerve palsies (CNP) and the development
of amblyopia.
Methods: We performed a retrospective chart review of 73 children diagnosed
with a CNP (III, IV, or VI) associated with a brain tumor who did not have any other
ophthalmic diagnoses which would impact visual acuity.
Results: Twenty children developed amblyopia (Group A) and had a mean age of 2.8
years at time of CNP diagnosis (range = 0.42 - 9.75 years, SD 2.3). Fifty-three children
did not develop amblyopia (Group B) and had a mean age of 7.9 years at time of CNP
diagnosis (range = 0.83 - 17.6 years, SD 4.6). The age at diagnosis was significantly
different between the two groups (p < 0.0001). Amblyopia developed in 67% of children
age 0-2 years at CNP diagnosis, in 50% at 2-4 years, in 18% at 4-6 years, in 9% at 6-8
years, and in 4% over 8 years. There was no significant difference between the two
groups with respect to tumor type, treatment, or motility and strabismus resolution
(overall 47% and 11%, respectively).
Conclusions: Children with CNP from brain tumors may be particularly susceptible to
amblyopia, as the strabismus from the CNP does not usually resolve. The likelihood of
amblyopia in young children suggests a role for more aggressive and/or prophylactic
amblyopia therapy in children under 4 years of age who develop CNP. Younger
children who develop CNP secondary to brain tumors are at high risk for developing
amblyopia.
CR: M.E. Hoehn, None; M.L. Bratton, None; N.C. Kerr, None.
Support: None
4751 - 4:15PM
Treatment of Amblyopia Using Macular Stimulation With Telescopic
Magnification
4750 - 4:00PM
Electrophysiological Detection of Delayed Post-Retinal Neural Conduction in
Amblyopia
E.C. Campos1, M.E. Scarale1, N. Balducci1, M. Fresina1, V. Parisi2. 1Ophthalmology Unit,
University of Bologna, Bologna, Italy; 2GB Bietti Foundation, IRCCS, Roma, Italy.
Purpose: Simultaneous recordings of pattern electroretinograms (PERG) and visual
evoked potentials (VEP) allow us to separate a macular dysfunction from a delay in
neural conduction along post-retinal visual pathaways1. Our work aims to evaluate the
macular function and the neural conduction along the visual pathways in amblyopic
patients.
Methods: 25 anisometropic amblyopic patients [mean age 7± 1.9 years; Visual Acuity
(VA): 0.44± 0.27 LogMAR in amblyopic eyes (AE), 0.023± 0.067 LogMAR in sound
eyes (SE)] and 25 age-similar controls (AS eyes, VA of 0.0± 0.0 LogMAR in both eyes)
were enrolled. In AE, SE and AS eyes, simultaneous PERG and VEP were recorded
in response to checks reversed at the rate of 2 reversals/s stimulating macular or
extramacular areas (the checks edge subtended 15’ and 60’of visual arc respectively)
2
.
Results: Non significant differences (ANOVA, p>0.01) in PERG and 60’ VEP responses
and in 60’ Retinocortical Time (RCT; difference between VEP P100 and PERG P50
implicit times) between AE, SE and AS eyes were observed. AE eyes showed a
significant (p<0.01) increase in 15’ VEP P100 implicit time and in 15’ RCT with respect
to the values observed in SE and AS. In amblyopic patients the interocular difference
in VA was significantly (Pearson’s Test, p<0.01) related to the interocular difference
in 15’ VEP P100 latencies and in 15’ RCT.
Conclusions: Our amblyopic eyes showed abnormal visual cortical responses only
when the macular area is stimulated (increase in 15’ VEP P100 implicit times). This
functional impairment, in presence of a normal macular function (15’ PERG responses
similar to control ones), can be ascribed to a delay in post-retinal neural conduction
(increase in 15’ RCT). The interocular differences in post-retinal neural conduction
were correlated to the interocular differences in visual acuity.
1
Celesia GG, Kaufman D, IOVS, 1985;26:726-35.
2
Tomoda H, Celesia GG, Toleikis SC. Electroencephalogr Clin Neurophysiol 1990;80:8188.
CR: E.C. Campos, None; M.E. Scarale, None; N. Balducci, None; M. Fresina, None; V.
Parisi, None.
Support: This work was supported in part through a grant from the Fondazione
Cassa di Risparmio in Bologna
4752 - 4:30PM
Natural History of Anisometropia and Its Association With Amblyopia
A.M. Wong, J. Wu, F. Nazemi, J. Schofield. Ophthalmology, Hospital for Sick
Children, Toronto, ON, Canada.
Purpose: A recent study (Nazami et al, 2008) suggested that telescopic magnification
improves visual acuity (VA) in older children with anisometropic amblyopia who have
failed previous treatment; however, a proper control group was lacking. The present
study aims to evaluate the effects of telescopic magnification on amblyopic patients,
and compare their results with those without telescope treatment.
Methods: Amblyopic patients, aged 4-17, who have failed previous treatment were
recruited. Inclusion criteria were: (1) VA 20/40-20/400 in the amblyopic eye; (2) VA
20/40 or better in the sound eye; (3) intraocular VA difference of at least 0.3 logMAR;
and (4) absence of any ocular pathology. Patients were randomly assigned to either 30
minutes of patching of the sound eye only daily (patching only group), or 30 minutes
of patching of sound eye plus concurrent use of a telescope (2.2x) on the amblyopic
eye daily (telescope group). Using a ETDRS logMAR chart, best corrected VA was
recorded at baseline and at 5 weeks after treatment.
Results: Thirteen patients were recruited. Seven patients were assigned to the patching
only group, and six to the telescope group. The mean baseline VA of patients in the
two treatment groups was similar (0.8 logMAR). There was no significant difference
in mean VA improvement between the telescope (0.22 logMAR) group and patching
only group (0.25 logMAR; p=0.69).
Conclusion: Treatment of refractory amblyopia in children using telescopic
magnification does not appear to be effective. Ongoing recruitment of more patients
and longer followup at 17 weeks would further clarify the effectiveness of this
treatment.
CR: A.M. Wong, None; J. Wu, None; F. Nazemi, None; J. Schofield, None.
Support: Hospital for Sick Children Jack Crawford Fund CT: If Other, enter the
registry site and corresponding number
S.H. Sharbini1A, K.A. Rose1A, G. Burlutsky1B, P. Mitchell1B, Sydney Childhood Eye
Study. ADiscipline of Orthoptics, BCentre for Vision Research, Department of
Ophthalmology and Westmead Millennium Institute, 1University of Sydney,
Sydney, Australia.
Purpose: To examine the natural history of anisometropia and its association with
amblyopia in a population-based random cluster sample of 6- and 12-year-old
students.
Methods: The Sydney Myopia Study randomly selected 55 primary and secondary
schools, stratified by socio-economic status (SES); 4069 children (70% response rate)
were examined. Cycloplegic autorefraction, LogMAR visual acuity, cover tests (cover/
uncover alternate, prism bar) at near and distance were performed. Anisometropia
was defined by the spherical equivalent [SE = spherical refraction + (0.5 X cylindrical
refraction)] and an astigmatic cylinder (AST) difference between the right and left eye
of >1.0 dioptre. Amblyopia was defined as best corrected visual acuity in the worse
eye less than 6/12 Snellen equivalent and/or a two line difference between the two
eyes. Cases included those present at time of examination, as well as those reported
by parents, and confirmed by a history of occlusion therapy.
Results: Anisometropia was present in 3.8% (n = 155) of the population and of
these 31.4% were amblyopic. There was a significant difference in the prevalence of
anisometropia in the 6-year-old (2.5%) compared with the 12-year-old (4.7%) children (p
= 0.0002). There were more amblyopic cases in the 6-year-olds (41.9%) than the 12-yearolds (27.9%).The number of amblyopic cases significantly increased with increasing
degrees of anisometropia in 1.0D steps >1.0D (23.7%), >2.0D (46.7%), >3.0D (66.7%) and
>4.0D (80.0%) (p < 0.0001).There was a marked increase in cases of amblyopia when
astigmatic refraction increased from 2.0D to 3.0D (10.8% to 50.0%, respectively), a trend
that continued with increasing refractive difference (p < 0.0001). The most frequent
type of anismometropia was myopic anismoetropia (46.8%) and the least common
was astigmatic anisometropia (21.2%).
Conclusions: Our study showed that the prevalence of anisometropia was higher
in the older than the younger group. 1D difference of anisometropia significantly
increased the risk of developing amblyopia. Astigmatic anisometropia degree of 3Ds
seemed to show a marked increase in the number of amblyopic cases.
CR: S.H. Sharbini, None; K.A. Rose, None; G. Burlutsky, None; P. Mitchell,
None.
Support: Australian NHRMC grant 253732
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4749-4752
Wednesday, May 6, 3:45 PM - 5:30 PM Palm A Paper Session Program Number Range: 4749 - 4755
463. Amblyopia II Organizing Section: EY
4753 - 4:45PM
Treatment of Severe Amblyopia With Atropine: Results From Two Randomized
Clinical Trials
4754 - 5:00PM
Massachusetts Preschool Vision Screening Program: Two Year Program
Evaluation
M.X. Repka1, R.T. Kraker2, R.W. Beck 2, E. Birch 3, S.A. Cotter4, J.M. Holmes5, R.W. Hertle 6,
D.L. Hoover7, D.L. Klimek 8, Pediatric Eye Disease Investigator Group. 1Ophthalmology,
Johns Hopkins Wilmer Eye Inst, Baltimore, MD; 2Jaeb Center for Health Research,
Tampa, FL; 3Retina Foundation of the Southwest, Dallas, TX; 4Southern California
College of Optometry, Fullerton, CA; 5Ophthalmology, Mayo Clinic, Rochester,
MN; 6Ophthalmology, Children’s Hospital of Pittsburgh, Pittsburgh, PA; 7Everett
and Hurite Ophthalmic Association, Pittsburgh, PA; 8Children’s Eye Care & Adult
Strabismus Surgery, South Charleston, WV.
J.E. Ramsey1, B. Moore2, A.H. Sheetz3, T. Comerford 3, L. McIntyre3. 1Ophthalmology,
Boston University School of Medicine, Boston, MA; 2New England College of
Optometry, Boston, MA; 3Massachusetts Dept of Public Health, Boston, MA.
Purpose: To determine the effectiveness of weekend atropine for severe amblyopia
from strabismus, anisometropia or both combined among children 3 to 12 years of
age.
Methods: We enrolled children into two prospective, randomized multi-center clinical
trials of amblyopia therapy. Herein we report the results for severe amblyopia, 20/125 to
20/400. In Trial 1, 60 children 3 to 6 years of age (mean age 4.4 years) were randomized
to weekend atropine plus a plano lens with weekend atropine with full spectacle
correction for the sound eye. In Trial 2, 40 children 7 to 12 years of age (mean age 9.3
years) were randomized to weekend atropine or two hours of daily patching. The visual
acuity outcome was assessed at 18 weeks in Trial 1 and 17 weeks in Trial 2.
Results: In Trial 1, visual acuity improved by an average of 4.5 lines in the atropine
plus correction group (95% confidence interval (CI) 3.2 to 5.8 lines) and 5.1 lines in
the atropine plus plano lens group (95% CI 3.7 to 6.4 lines). In Trial 2, visual acuity
improved by an average of 1.5 lines in the atropine group (95% CI 0.5 to 2.5 lines) and
1.8 lines in the patching group (95% CI 1.1 to 2.6 lines).
Conclusions: Atropine can improve visual acuity in children 3 to 12 years of age with
severe amblyopia. Improvement may be greater in younger children.
CR: M.X. Repka, None; R.T. Kraker, None; R.W. Beck, None; E. Birch, None; S.A.
Cotter, None; J.M. Holmes, None; R.W. Hertle, None; D.L. Hoover, None; D.L.
Klimek, None.
Support: NIH Grant EY011751 CT: www.clinicaltrials.gov, NCT00315328
Purpose: To evaluate the Massachusetts Preschool Vision Screening Program two
years after implementation.
Methods: Following a legislative mandate, the Massachusetts Preschool Vision
Screening Program was developed, based on a “medical home” model where preschool
children receive vision screening by the primary care provider. In addition, the
school nurses provided a backup support system. Working in collaboration with the
Massachusetts Department of Public Health, an aggressive state-wide educational
campaign was developed and targeted to pediatric primary care providers and
school nurses. Two years after initiation of the program, a randomized phone survey
of 100 primary care pediatric practices was conducted. In addition, a mail survey of
pediatric healthcare providers was conducted in both 2005 and 2007. Comparative data
was able to be obtained. An on-line survey tool inquiring about both the frequency
and quality of vision screening was developed and targeted to school nurses; data
was reported for 29,811 preschool children. Additional school nurse information
was obtained on nearly 11,000 enrolled kindergarten students from a self-selected
cohort of nurse leaders.
Results: Ninety nine percent of the primary care physicians contacted in the
randomized phone survey indicated that they were aware of the new mandated
preschool vision screening program and 89% reported that they were implementing
the program. The mail survey from 2007 showed a significant increase in the number
of physicians who reported use of the mandated vision screening protocol compared
with 2005: picture symbol use declined and HOTV/Lea symbol use increased from
18% to 65%. Stereo testing, part of the recommended protocol, increased from 15%
to 85%. 65% reported using recommended methods of ocular occlusion compared
with 11% at baseline.
Results from the school nurse surveys showed an increase in the number of preschoolers
screened by primary care providers, from 44% in 2005 to 62% in 2007.
Conclusions: Two years after the Massachusetts Preschool Vision Screening Program
was initiated, there has been an increase in both the rates and quality of preschool
vision screening.
CR: J.E. Ramsey, None; B. Moore, None; A.H. Sheetz, None; T. Comerford, None; L.
McIntyre, None.
Support: Massachusetts Department of Public Health
4755 - 5:15PM
Polarization Modulation Using Wave Plates to Enhance Foveal Fixation
Detection in Retinal Birefringence Scanning for Strabismus Screening
Purposes
K. Irsch1,2, B.I. Gramatikov2, Y.-K. Wu2, D.L. Guyton2. 1Kirchhoff Institute for Physics,
University of Heidelberg, Heidelberg, Germany; 2The Wilmer Eye Institute, The
Johns Hopkins University School of Medicine, Baltimore, MD.
Purpose: To enhance foveal fixation detection while bypassing the deleterious effects of
corneal birefringence in binocular retinal birefringence scanning (RBS) for strabismus
screening purposes, a new RBS design was developed incorporating a double-pass
spinning half wave plate (HWP) combined with a fixed double-pass wave plate (WP)
into the optical system.
Methods: The incorporation of the spinning HWP effectively enables differential
polarization detection with only one detector, and together with a fixed WP the
differential polarization signal can be detected essentially independently of various
amounts and orientations of corneal birefringence that occur in the population.
Utilizing the measured corneal birefringence from a data set of 300 human eyes, an
algorithm and related computer program were developed in MATLAB for optimizing
the properties of both wave plates to statistically maximize the foveal fixation signal,
while having the greatest independence from left and right eye corneal birefringence.
The computer model was verified with experimental human data using an intermediate
RBS-based eye fixation monitor.
Results: Foveal fixation detection was optimized with the HWP spun 9/16 as fast as
the circular scan, with the fixed WP having a retardance of 45° and fast axis at 90°.
With this optimized RBS design, a significant statistical improvement of 7.3 times
in signal strength, i.e. FFT power, was achieved for the available data set compared
with the previous RBS design. Validation experiments confirmed the model’s ability
to find the optimum amount of double-pass retardance necessary to yield maximal
signal strength for the investigated range of corneal birefringence.
Conclusions: The computer-model-optimized RBS design greatly enhances foveal
fixation detection. Combining a binocular eye fixation monitor based on this new
RBS design with bull’s-eye focus detection promises to be both robust and sensitive
in screening infants automatically and reliably for both of the primary causes of
amblyopia: strabismus and defocus.
CR: K. Irsch, None; B.I. Gramatikov, None; Y.-K. Wu, None; D.L. Guyton, The Johns
Hopkins University School of Medicine, P.
Support: Robert and Maureen Feduniak, Dewey and Janet Gargiulo, David and
Helen Leighton, Richard and Victoria Baks, Robert and Diane Levy, and Research to
Prevent Blindness (DLG).
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
4753-4755
Thursday, May 7, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 5344 - 5356 / A295 - A307
517. Optic Neuropathy I Organizing Section: EY
5344 - A295
Bilateral Optic Atrophy: A Background Finding in Cynomolgus Macaques Used
in Toxicologic Research
5345 - A296
Immunohistochemical Study of the Receptor for Advanced Glycation End
Products in the Microvasculature of Alzheimer’s Optic Nerves
R.R. Dubielzig1A, R. Leedle2, T.M. Nork1B, J.A. VerHoeve1B, B.J. Christian2. APathobiol
Sciences and CORL, BOphthalmolgy and Visual Sciences and CORL, 1Univ of
Wisconsin-Madison, Madison, WI; 2Pathology, Covance Laboratories Inc, Madison,
WI.
M.Y. Wang, F.N. Ross-Cisneros, A.A. Sadun. Neuro-Ophthalmology, USC/Doheny
Eye Institute, Los Angeles, CA.
Purpose: The incidence, funduscopic findings, electroretinographic (ERG), flash visual
evoked potential (VEP), and histopathologic findings of bilateral optic atrophy found
in cynomolgus macaques used in regulatory toxicologic research are described.
Methods: Cynomologus macaques randomly chosen as a test system for regulatory
toxicologic studies had backgound lesions typical of bilateral optic atrophy, a condition
previously described only in Rhesus macaques. Fundus photography, ERG, and
Flash VEP were performed using standard techniques in some of the animals and
histopathology was performed in all animals.
Results: All of the affected animals were 2 to 3 years old and the large majority were of
Vietnamese origin. In various studies between 0% and 24% of animals were affected.
In one study with 14 affected animals, the histomorphological appearance exhibited a
range of severity as follows: severe (6), moderate (3), slight (3) and minimal (2). 4 of the 6
with severe disease and 1 of the 3 with slight disease had optic nerve atrophy recorded
on the screening fundus photography; all other animals were considered within the
limits of normal variation. Affected animals were not detected by standard ERG or
Flash VEP in this study. The morphologic changes consist of a decrease in ganglion
cells in the macula and a decrease in axons in the temporal nerve fiber layer and the
temporal optic nerve. The condition was always unrelated to the administration of test
compounds. No affected animals had any detectable behavioral abnormalities.
Conclusions: Bilateral optic atrophy has been reported in Rhesus macaques originating
from China. We report the occurrence of the a similar syndrome in cynomolgus
macaques of Vietnamese origin. Given the cynomolgus macque is commonly used
in ophthalmic drug safety studies, it is important to characterize the nature of the
finding. While the abnormality was not detected by ERG or flash VEP, the majority
of markedly affected eyes could be identified by fundus evaluation.
CR: R.R. Dubielzig, None; R. Leedle, Covance Laboratories Inc N, E; T.M. Nork,
None; J.A. VerHoeve, None; B.J. Christian, Covance Laboratories Inc N, E.
Support: None
Purpose: Several studies have suggested that the receptor for advanced glycation end
products (RAGE) are up-regulated in the microvasculature of Alzheimer’s disease
(AD) to actively mediate the transport of β-amyloid across the blood-brain barrier into
the brain from the systemic circulation. Once bound, the interaction of β-amyloid and
RAGE could lead to a chronic inflammatory state amplified and perpetuated by the
RAGE axis. The goal of this study is to determine whether there is any increase in the
expression of RAGE in the microvasculature of the Alzheimer’s optic nerves.
Methods: We looked at 10 retrobulbar optic nerves (1-3 mm from the globe) from
donors previously diagnosed with AD. These were compared to 5 age-matched
control optic nerves from individuals with no AD. All tissues were formalin-fixed
and embedded in paraffin. Tissue sections were cut at 5 µm and immunostained with
antibodies directed against human RAGE and endothelia (CD-31) both individually
(immunoperoxidase) and for colocalization of these antigens (immunofluorescence)
within optic nerve microvasculature. Tissue sections were observed on a standard
bright field (immunoperoxidase) and confocal (immunofluorescence) microscope .
The intensity and localization of immunolabeling for RAGE was qualitatively graded
on a scale from 0 to 3. Grade 0 was defined as no staining, Grade 1 as mild staining,
Grade 2 as moderate staining, and Grade 3 as strong staining.
Results: Immunoreactivity for RAGE and endothelia were well defined. The
immnolabelling for RAGE appeared “punctate” and the label for endothelia (CD-31)
outlined their course within optic nerve connective tissue and fiber bundle parenchyma.
In AD optic nerves, there was moderate to strong staining (Grade 2 and 3) for RAGE
within the microvasculature, frequently outlining the blood vessels. In contrast, the
staining for RAGE was largely minimal (Grade 1-2) in the microvasculature of control
nerves. RAGE appeared to increase with age in both groups.
Conclusions: Our observations suggest that AD is associated with an increase in
RAGE within the microvasculature of the optic nerve. RAGE is a multi-ligand receptor
that can bind to β-amyloid and other pro-inflammatory ligands. We postulate that
the increase in RAGE within the microvasculature of AD optic nerve may contribute
to the pathogenetic processes of optic neuropathy observed in a subpopulation of
these patients.
CR: M.Y. Wang, None; F.N. Ross-Cisneros, None; A.A. Sadun, None.
Support: Oakley Alzheimer’s Research Foundation, Research to Prevent Blindness
and NIH Grant EY03040
5346 - A297
An Immunohistochemical (IHC) Examination of Role of N-Methyl D- Aspartate
(NMDA) Receptor as a Mediator of Damage in Optic Nerves of Patients with
Chronic HIV Infection
5347 - A298
Follow-Up of Pattern-Reversal Visually Evoked Potential in Non-Affected
Carriers From an Extensive Brazilian Leber Hereditary Optic Neuropathy
(LHON) Pedigree
M. Singh1, A. Shariati1, F.N. Ross-Cisneros1, W.R. Freeman2, A.A. Sadun1. 1NeuroOphthalmology, USC/Doheny Eye Institute, Los Angeles, CA; 2Ophthalmology,
University of California San Diego, La Jolla, CA.
P.Y. Sacai1, A. Berezovsky1, J.M. Pereira1, S.E.S. Watanabe1, L.D. Alves1, N.N. Cavascan1,
R. Belfort, Jr.1, V. Carelli2, A.A. Sadun 3, S.R. Salomao1. 1Ophthalmology, Federal
University of Sao Paulo, Sao Paulo, Brazil; 2Neurological Sciences, University of
Bologna, Bologna, Italy; 3Doheny Eye Institute, University of Southern California,
CA.
Purpose: To determine if activation of NMDA receptors plays a role in the damage
of optic nerves of the patients chronically infected with HIV.
Methods: 28 retro bulbar optic nerves were collected at autopsy from 14 patients
previously established to have chronic HIV infection. Six age matched control
retro bulbar optic nerves were also collected. The nerves were immersion-fixed in
10% formalin. 3mm cross-sections of the nerves were embedded into paraffin and
then cut on a microtome at 4microns. A two step indirect IHC staining method
was employed using an HRP-conjugated secondary antibody reacting with a DAB
substrate-chromogen system. The Primary antibody directed against human NMDA
was diluted to 1:20. The slides were analyzed using a Zeiss Axioskop light microscope.
The optic nerve’s IHC staining was graded on a scale from 0 to 4. 0 staining appeared
to have none, or very trace evidence of DAB+ staining within the optic nerve tissue
and the surrounding dura. A 4 appeared to have specific , heavy staining throughout
the optic nerve.
Results: We examined 38 nerves from 14 HIV patients. 4 of the 28 patients had a Grade
4 positive staining. Positive staining of NMDA was found in the neural tissue of HIV
nerves as well as the control nerves, but the density of the staining was found to be
more in the HIV nerves than in the negative control nerves. The density of NMDA
receptors as evidenced by staining shows a continuum from being more dense to a
decreasing density as the apoptotic process continues and neural tissue drop out
occurs. These nerves ultimately show degeneration.
Conclusions: The optic nerves of HIV positive patients have an up regulation of NMDA
receptors which leads to excitotoxic injury to these nerves leading to cell loss and
degeneration. This study shows the evidence of optic nerve damage in HIV positive
patients as a result of NMDA receptor activation by the viral proteins.
CR: M. Singh, None; A. Shariati, None; F.N. Ross-Cisneros, None; W.R. Freeman,
None; A.A. Sadun, None.
Support: Research to Prevent Blindness, and NIH Grants EY03040
Purpose: LHON is a maternally inherited disease associated with mitochondrial DNA point
mutations and characterized by profound bilateral loss of central vision. Subclinical visual
abnormalities have been reported in psychophysical and clinical assessment in asymptomatic
of non-affected LHON carriers. The purpose of this longitudinal study was to investigate
possible subclinical abnormalities by pattern-reversal visual evoked potential (PRVEP) in
non-affected carriers from an extensive Brazilian 11778 LHON pedigree.
Methods: Transient PRVEP (reversal rate = 1.9Hz; checkerboard stimuli 15’ and 60’; 100%
contrast) was recorded from each eye in 15 non-affected carriers, aging from 19-57 years
(mean= 38.7±12.3 yrs; median= 38.9; 10 females) in three visits (2002, 2006 and 2008). All
participants had best corrected visual acuity of 20/20. In the first visit, an additional control
group of 26 healthy subjects aging from 20-60 years (mean= 36.8±10.6 yrs; median= 35.7; 14
females) was tested. Latency (ms) of N75, P100 and N135 peaks and N75-P100 amplitude (µV)
were determined for both stimuli size. Temporal dispersion of the response was calculated by
the difference in latency between N135 and N75. Mann-Whitney test was used for comparison
between carriers and controls. Kruskal-Wallis one-way analysis of variance was used to
compare the three visits follow-up measurements.
Results: In the first visit, statistically prolonged latencies were found in carriers when
compared to controls with stimulus size 15’ (P=0.030) for P100 and N135 (P<0.001) and with
stimulus size 60’ for N135 (P=0.004). Widened response was found in carriers when compared
to controls with 15’and 60’stimuli size (P=0.013 and P=0.017, respectively). No differences
were found for N75-P100 amplitudes between carriers and controls for both stimulus sizes.
Intra-subject analysis for P100 latency and temporal dispersion was comparable in the
three visits.
Conclusions: Subclinical PRVEP abnormalities characterized by consistently prolonged
latencies were found in asymptomatic non-affected carriers from this large 11778 LHON
pedigree. Prolonged P100 latencies and larger temporal dispersion remain as persistant
evidence of subclinical changes.
CR: P.Y. Sacai, None; A. Berezovsky, None; J.M. Pereira, None; S.E.S. Watanabe, None; L.D.
Alves, None; N.N. Cavascan, None; R. Belfort, Jr., None; V. Carelli, None; A.A. Sadun,
None; S.R. Salomao, None.
Support: International Foundation for Optic Nerve Disease (IFOND)
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
5344-5347
Thursday, May 7, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 5344 - 5356 / A295 - A307
517. Optic Neuropathy I Organizing Section: EY
5348 - A299
The Pattern of Abnormal Multifocal Visual Evoked Potential Latencies Involves
Ceocentral and Arcuate Nerve Fiber Regions in Patients With Recovered Optic
Neuritis
E. Rosenblat1,2, F. Levin1, J.G. Odel1, D.C. Hood 3. 1Department of Ophthalmology,
College of Physicians and Surgeons, New York, NY; 2Albert Einstein College of
Medicine, Bronx, NY; 3Departments of Psychology and Ophthalmology, Columbia
University, New York, NY.
Purpose: To compare the pattern of visual field loss obtained with static automated
perimetry (SAP) to the pattern of increased latency of the multifocal visual evoked
potential (mfVEP) in patients with recovered optic neuritis (ON).
Methods: 20 eyes of 20 patients with ON, ranging in age from 25 to 54, who
underwent both mfVEP and 24-2 SAP testing within a 2 month period, were identified
retrospectively. Patients with an attack within 6 months of testing were excluded.
All patients had a visual acuity of 20/25 or better. Pattern reversal mfVEPs were
recorded in response to a 44° diameter, 60 sector dartboard pattern (VERIS, EDI) using
a montage of 4 electrodes as previously described.[1] The latency of the responses
for each sector was calculated with a computer algorithm and compared to control
values.[2] The locations of abnormal (p<5%) mfVEP latencies were displayed on
monocular and intraocular probability plots [2], which were combined to show all
abnormal points. The number of abnormal points was tabulated at each location. The
number of abnormal (p<5%) points at each location was likewise tabulated for the
total deviation SAP plot.
Results: There were a significantly higher percentage of abnormal points on the
mfVEP latency plots than on the SAP visual fields. 48.0% of the sectors of the mfVEP
had abnormally long latencies, while 20.1% of the visual field locations on SAP were
abnormal. Further, only 25.0% of the patients had abnormal mean deviations on
SAP, while 95% of patients had significant mean mfVEP delays.[3] The most common
locations of increased latency in the mfVEP were in the cecocentral and inferior arcuate
regions. For the SAP fields, there were an insufficient number of abnormal points to
confidently determine a pattern.
Conclusion: The pattern of field locations with abnormally prolonged mfVEP latencies
involved the cecocentral and arcuate nerve fiber bundle regions. These abnormalities
were more severe than those seen on the SAP visual fields [4] and approximated both
the pattern recently reported for the acute stage of optic neuritis on SAP visual fields [5]
and the classic pattern of cecocentral involvement found at the tangent screen.[6]
1. Hood, Zhang, et al. IOVS, 2000; 2. Hood, Ohri, et al. Doc Ophthal,2004; 3. Hood,
Chen, et al. TAOS, 2006; 4. Hood, Odel, Zhang IOVS, 2000; 5. Nevalainen, Krapp, et
al. Graefes, 2008; 6. Chamlin Arch Ophthal, 1953.
CR: E. Rosenblat, None; F. Levin, None; J.G. Odel, None; D.C. Hood, None.
Support: NIH Grant EY02115
5349 - A300
Spike Gene Mediates Viral-Induced Experimental Optic Neuritis
K.S. Shindler1, M. Dutt1, J. Das Sarma2. 1Ophthalmology, Univ Pennsylvania Scheie
Eye Institute, Philadelphia, PA; 2IISER-Kolkata, Kolkata, India.
Purpose: Infection of mice with neurovirulent strains of mouse hepatitis virus (MHV)
is used as a model for virus-induced demyelination that mimics many pathologic
features of multiple sclerosis. A significant incidence of optic neuritis occurs in mice
infected with a demyelinating strain of MHV (MHV-A59), but not with the nondemyelinating strain, MHV-2. Mechanisms underlying this differential induction of
optic neuritis are not known. We examined the potential role of spike, a glycoprotein
involved in virus-host attachment, in mediating induction of optic neuritis.
Methods: Four week-old C57Bl/6 mice were inoculated intracranially with 50% LD50
dose of RSA59 strain (20,000 PFUs) or RSMHV2 (100 PFUs). RSA59 and RSMHV2
strains of MHV are isogenic (background is from demyelinating strain MHV-A59)
except for the spike gene. Mice were sacrificed 5 and 30 days post-innoculation. 5
micron longitudinal sections of isolated optic nerves were assessed by H & E and
immunohistochemistry for inflammatory cell markers. Axonal integrity was assessed
by silver staining.
Results: RSA59 induced optic neuritis, characterized by inflammatory cell infiltration
of optic nerves, by day 5 post-innoculation, with significant loss of myelin and axonal
damage detected at day 30, similar to effects of the parent virus MHV-A59 seen in
prior studies. RSMHV2, however, induced little or no optic nerve inflammation with
preserved myelin and retinal ganglion cell axons.
Conclusions: Results demonstrate that a neurovirulent spike gene is required for
MHV strains to induce optic neuritis, as the spike gene from the non-demyelinating
MHV2 strain rendered MHV-A59 incapable of inducing optic nerve inflammation,
demyelination and axonal damage. The spike protein is a potential target for disrupting
virus-host attachment that may have a role in treating optic neuritis and multiple
sclerosis.
CR: K.S. Shindler, None; M. Dutt, None; J. Das Sarma, None.
Support: NIH grant EY015098, a Career Development Award from RPB, and the F. M.
Kirby Foundation to KSS; FG1431-A-1 and RG3774A2-1 from the NMSS, and M.E.Groff
Surg. Med. Res. and Ed. Charitable Trust to JDS
5350 - A301
Optic Nerve Size May Reflect Pattern of Axonal Degeneration in Leber’s
Hereditary Optic Neuropathy
5351 - A302
Immunohistochemical Study of High Mobility Group Box 1 in Alzheimer’s
Disease Optic Nerves
K.R. Tozer1, C.D. Robinson1, D. Aggarwal1, F.N. Ross-Cisneros1, M.N. Moraes-Filho2, A.
Berezosky3, S.R. Salomao3, V. Carelli4, A.A. Sadun1. 1Neuro-Ophthalmology, Doheny
Eye Institute and Keck School of Medicine, University of Southern California, Los
Angeles, CA; 2Instituto de Olhos de Colatina, Colatina, Brazil; 3Ophthalmology,
Federal University of Sau Paulo, Sau Paulo, Brazil; 4Dipartimento di Scienze
Neurologiche, Universitá di Bologna, Bologna, Italy.
A.B. Savoia, D. Aggarwal, F.N. Ross-Cisneros, A.A. Sadun. Neuro-Ophthalmology,
USC/Doheny Eye Institute, Los Angeles, CA.
Purpose: To perform a morphometric analysis of four optic nerves from two related
Leber’s Hereditary Optic Neuropathy (LHON) patients and study the pattern of
degeneration in relationship to different states of disease progression.
Methods: Optic nerves from two LHON (11778/ND4 mtDNA mutation) affected
brothers with moderate and severe optic atrophy respectively were studied and
compared. Both patients had been followed as part of a large systematic prospective
ophthalmological investigation of LHON. The optic nerves were fixed, plastic
embedded, and stained with p-phenylenediamine to allow for axon counting. For total
axon counts, a nerve cross section was partitioned into five different regions. Photos
were taken at 1000X magnification and axons were counted by hand. Total counts
and axon densities were calculated. Total cross sectional areas were also calculated
for the optic nerves using the “Spot II Advanced” software package.
Results: Two different degeneration patterns were observed. One brother (patient 1)
had a focal area of degeneration in the temporal zone of both eyes with sparing of the
periphery, while the other brother (patient 2) had a diffuse pattern of degeneration.
Total axon counts per optic nerve for patient 1 were 333,192 (OD) and 269,319 (OS)
while patient 2 had counts of 22,889 (OD) and 22,376 (OS). The cross sectional area
of the optic nerves were 5.79(OD) and 7.97 (OS) mm 2 for patient 1, and 3.29(OD) and
3.35(OS) mm 2 for patient 2.
Conclusions: This study provides morphometric evidence of the relationship between
different stages of LHON and optic nerve size. Since both patients showed extensive
levels of degeneration well below the approximately 1.0 million axon per optic nerve
average for this age group (Johnson, et. al; Age 1987), it is not likely that the entire
difference in nerve size can be attributed to the level of degeneration. Hence, even
taking into account that increased degeneration leads to more atrophic shrinkage
of the optic nerve, a smaller, and thus more crowded, optic nerve may be associated
with more severe and diffuse patterns of degeneration.
CR: K.R. Tozer, None; C.D. Robinson, None; D. Aggarwal, None; F.N. Ross-Cisneros,
None; M.N. Moraes-Filho, None; A. Berezosky, None; S.R. Salomao, None; V. Carelli,
None; A.A. Sadun, None.
Support: None
Purpose: To investigate the presence of High Mobility Group Box 1 (HMGB1) in
Alzheimer’s disease (AD) optic nerves. HMGB1 is a non-histone DNA binding protein
which can translocate from the nucleus to the cytoplasm during states of cellular stress
or damage. It can then act as both a cytokine and ligand stimulating the receptor for
advanced glycation end products (RAGE) when released extracellularly resulting in
inflammation and tissue damage.
Methods: Optic nerve specimens were obtained at autopsy from twelve patients with
AD and compared to six normal age-matched control tissues. AD tissues were supplied
by our Alzheimer’s Disease Research Center (ADRC) and controls were purchased
through local eye banks. Tissues were immersion fixed in neutral buffered formalin,
dissected into cross-sectional profiles just proximal to the globe, then processed and
embedded into paraffin blocks. Sections were cut at 5 µm and immunostained, using an
indirect method with horseradish peroxidase and diaminobenzidine as the substratechromogen, with a rabbit anti-human HMGB1 polyclonal antibody at a dilution of
1:1,000. Light microscopic images were viewed on a Zeiss Axioskop microscope and
captured by a digital camera and saved to a computer.
Results: Control optic nerves immunostained for HMGB1 demonstrated very specific
nuclear but not cytoplasmic staining in most cells. AD tissues revealed both nuclear
and cytoplasmic localization of the chromogen. The cytoplasmic staining was usually
intense and highlighted this region’s entire area. It was also observed that the cell
cytoplasm appeared vacuolated with an empty space often circumscribing the
entire, though intact, nucleus. Glial cells appeared to be the primary target of the
immunostaining with astrocytes being the most common glial cell labeled.
Conclusions: HMGB1 is a non-histone DNA binding protein that can act as a ligand to
RAGE which can initiate pro-inflammatory pathways. Increased presence of HMGB1
in cytoplasm of glial cells in AD optic nerves may indicate that HMGB1, when released
extracellularly, may bind to RAGE thus mediating inflammatory pathways. Hence,
HMGB1 may play a role in the pathogenesis of optic neuropathy as observed in a
subpopulation of Alzheimer’s disease patients.
CR: A.B. Savoia, None; D. Aggarwal, None; F.N. Ross-Cisneros, None; A.A. Sadun,
None.
Support: Research to Prevent Blindness, Oakley Alzheimer’s Research Foundation,
NIH Grant EY03040
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
5348-5351
Thursday, May 7, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 5344 - 5356 / A295 - A307
517. Optic Neuropathy I Organizing Section: EY
5352 - A303
Comparison of Humphrey Matrix Frequency Doubling Technology in the
Assessment of Pre-Chiasmal and Post-Chiasmal Disease
5353 - A304
Novel Applications of Rarebit Perimetry
M.K. Yoon, C. Kum, S. Day, T.J. McCulley. Ophthalmology, University of California San Francisco, San Francisco, CA.
S.K. Houston, III1A, E.D. Weber1B,2, S.A. Newman1B, S.F. Koga1C. ASchool of Medicine,
B
Ophthalmology, CNeurosurgery, 1University of Virginia, Charlottesville, VA;
2
Ophthalmology, Walter Reed Army Medical Center, Washington, DC.
Purpose: Frequency doubling technology perimetry (FDT) has been used to assess
visual function in patients with neuro-ophthalmic abnormalities of the anterior and
posterior visual pathways. Initial reports suggested that FDT is less accurate assessing
defects of the posterior visual pathway. In this study, we compared Humphrey Matrix
FDT to standard automated perimetry (SAP) in the assessment of pre- and postchiasmal disease.
Methods: The charts of all patients with neuro-ophthalmic disease, involving the
anterior (n=27) and posterior (n=9) visual pathways, tested with both Humphrey
Matrix FDT (30-2) and Humphrey Visual Field Analyzer (30-2 SITA standard) from
July 2006 to November 2008, were retrospectively reviewed. Involved eyes of unilateral
disorders were included; the better and worse eyes were alternated in bilateral disease.
Similarity between the tests were numerically graded 1 (poor), 2 (fair), and 3 (good)
for total (TD) and pattern deviation (PD) plots. Additionally, the extent of defects were
compared, with more extensive field loss defined as 5 or more abnormal test locations
at P < 0.5%. Spearman coefficient was calculated for both mean deviation (MD) and
pattern standard deviation (PSD).
Results: Etiologies included compressive lesions (n= 11), NAION (n= 5), stroke (n= 4),
IIH (n=3), optic nerve drusen (2), and other (n= 11). The average similarities between
the FDT and SAP for PD in anterior and posterior disease were 2.31 and 2.44 (p = 0.44,
paired T-test); and for TD were 2.46 and 2.5, respectively (p = 0.29). The extent of defect
was same in 55% on PD and 66% on TD. Spearman coefficient for anterior and posterior
disease for MD was 0.86 and 0.93, and for PSD was 0.78 and 0.63, respectively.
Conclusions: Although originally developed for glaucomatous field defects, the
Humphrey Matrix perimeter has reasonable correlation to SAP in anterior and
posterior pathway disease. Our series, which uses 30-2 field analysis, demonstrates
fair to good correlation between SAP and FDT in both anterior and posterior neuroophthalmic disease. This suggests that the poor correlation with earlier versions of
FDT was due to technical aspects of the perimeter, and not due to differing aspects
of visual function being tested by FDT and HVF.
CR: M.K. Yoon, None; C. Kum, None; S. Day, None; T.J. McCulley, None.
Support: That Man May See
Purpose: Rarebit perimetry (RBP) was developed for the detection of early damage to
the afferent visual system. Testing is performed on a standard personal computer with
a 15” LCD screen and utilizes suprathreshold stimuli that probe for the completeness
of the neuroretinal architecture. Previous studies have shown that RBP is able to
detect visual field defects in glaucoma and neuro-ophthalmologic disorders. Rarebit
perimetry has also been shown to be more sensitive to early and subtle damage to the
afferent system compared to standard automated perimetry (SAP). The purpose of
the study was to determine the feasibility of bedside testing with rarebit perimetry
and compare results with standard automated perimetry.
Methods: 29 eyes of 15 patients admitted with neurologic or neurosurgical disease
affecting the afferent visual system were tested. Visual fields using RBP were tested
on a laptop computer at the bedside, while visual fields tested using SAP (Humphrey
field analyzer) were performed in the clinic.
Results of the two tests were compared by a neuro-ophthalmologist blinded to the
diagnosis.
Results: 21 of 29 (72%) visual fields corresponded between RBP and SAP. Additionally,
RBP detected 5 defects (17%) in patients who had normal results on SAP. Finally, 15
of 15 patients preferred RBP for ease of testing and convenience.
Conclusions: Rarebit perimetry is an easy, convenient, and reliable way to test the
afferent visual pathways at the bedside.
CR: S.K. Houston, III, None; E.D. Weber, None; S.A. Newman, None; S.F. Koga,
None.
Support: None
5354 - A305
Age-Corrected Normative Data for the Entire (80 Degree) Visual Field, Assessed
With a New Fast Thresholding Estimation (GATE)
5355 - A306
Comparison Between Age-Corrected Normative Threshold Values for the Static
Stimulus Sizes Goldmann III and V, Assessed With a New Fast Thresholding
Estimation (GATE)
U. Schiefer1, S. Frick1, J. Nevalainen2, J. Grobbel1, E. Krapp1, B. Selig1, R. Vonthein 3, R.G.
Weleber4, J. Paetzold1. 1Institute for Ophthalmic Research, Centre for Ophthalmology,
Tuebingen, Germany; 2University Eye Hospital Oulu, Oulu, Finland; 3Institute of
Medical Biometry and Statistics, University of Luebeck, Luebeck, Germany; 4Casey
Eye Institute, Oregon Health & Science University, Portland, OR.
Purpose: To assess age-corrected normative differential luminance sensitivity (DLS)
values for automated static perimetry with a new, fast strategy (GATE = German
Adaptive Threshold Estimation) for the entire (80 degree) visual field.
Methods: Eighty-one normal subjects, aged from 10 to 79 years were enrolled in this
study, which was performed on the new Octopus 900 perimeter (HAAG-STREIT Inc.,
Koeniz, Switzerland). Eighty-six static stimuli (Goldmann size III = 26´) up to a maximal
eccentricity of 80 degrees, with a condensation towards the visual field centre, were
presented on a homogeneous background under photopic conditions (luminance
level 10 cd/m²). A fast thresholding 4-2 dB algorithm with at least one reversal was
used. Local DLS values were estimated by applying the maximum likelihood (ML)
procedure. A smooth mathematical model was fitted to the data set, allowing to predict
the local DLS values for any location of the entire visual field.
Results: Model fit was satisfactory (R² = 0.72). The residual standard deviation over
the entire 80 degree visual field amounted to 2.52 dB. The number of questions asked
(mean) was 338 for the GATE strategy (compared to 410 for the conventional 4-2 dB
bracketing algorithm) in this cohort of normal subjects. Examination duration (median,
without breaks) was 13.5 min. (95% RI 10.7 - 20.4 min).
Conclusions: A smooth mathematical model allows for the prediction of local
differential luminance thresholds of normal subjects for any location within the
entire 80 degree visual field, obtained with the new Octopus 900 perimeter. In normal
subjects, the new, fast GATE strategy reduces the number of questions asked by
approximately 18%, compared to a full threshold bracketing algorithm. Subsequent
examinations with GATE are related to previous exams and therefore further reduce
the examination duration.
CR: U. Schiefer, Haag-Streit, Koeniz, Switzerland, C; S. Frick, None; J. Nevalainen,
None; J. Grobbel, None; E. Krapp, Haag-Streit, Koeniz, Switzerland, F; B. Selig,
None; R. Vonthein, None; R.G. Weleber, None; J. Paetzold, Haag-Streit, Koeniz,
Switzerland, F.
Support: Haag-Streit CT: If Other, enter the registry site and corresponding
number
J. Dietzsch1, J. Grobbel1, J. Nevalainen2, S. Frick1, E. Krapp1, B. Selig1, R. Vonthein 3,
R.G. Weleber4, J. Paetzold1, U. Schiefer1. 1Centre for Ophthalmology, Institute of
Ophthalmic Research, University of Tuebingen, Tuebingen, Germany; 2University
Eye Hospital Oulu, Oulu, Finland; 3Institute of Medical Biometry and Statistics,
University of Luebeck, Luebeck, Germany; 4Casey Eye Institute, Oregon Health &
Science University, Portland, OR.
Purpose: To assess the differences of the age-corrected normative differential
luminance sensitivity (DLS) values for automated static perimetry with Goldmann
stimulus size III and V using GATE (German Adaptive Threshold Estimation).
Methods: Sixty-six normal subjects (10 to 79 years) were examined with the Octopus
900 perimeter. The grid of 86 test locations up to 80 degrees was condensed towards the
center of the visual field. Static stimuli of Goldmann size III and size V were presented
during two sessions on a photopic background (10 cd/m²). The fast thresholding
algorithm GATE was used with an initial step size of 4 dB and at least one reversal.
DLS values were estimated by applying the maximum likelihood (ML) procedure.
Two smooth mathematical models were fitted separately to the two data sets, in order
to predict the local DLS values for any location of the entire visual field.
Results: The difference between the predicted DLS values (V-III) was calculated to
assess the differential shape of the fitted models. This difference varied depending
on the age from +3 dB to +5 dB in the center, showed an interaction between age and
eccentricity outside the center, and in the periphery ranged from +8 dB to +11 dB.
Conclusions: A smooth mathematical model
allows the estimation of the differences in
measuring the normative local DLS thresholds.
For normal subjects a DLS difference (V-III) of
approximately +3 dB to +5 dB can be observed
in the centre of the visual field. The DLS
difference was greatest in the periphery,
decreases with the age for low eccentricity
values, and increases with age for high
eccentricity values.
CR: J. Dietzsch, Heidelberg Engineering, F; J. Grobbel, None; J. Nevalainen, None; S.
Frick, None; E. Krapp, None; B. Selig, None; R. Vonthein, None; R.G. Weleber, None;
J. Paetzold, Haag-Streit, F; U. Schiefer, Haag-Streit, C.
Support: Heidelberg Engineering, Haag-Streit CT: If Other, enter the registry site
and corresponding number
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
5352-5355
Thursday, May 7, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 5344 - 5356 / A295 - A307
517. Optic Neuropathy I Organizing Section: EY
5356 - A307
Three-Dimensional Optic Nerve Learning Module for Physicians in Training
A.S. Khouri1, R.D. Fechtner1, J.M. Liebmann2. 1Ophthalmology, UMD New Jersey
Medical School, Newark, NJ; 2Ophthalmology, New York Eye and Ear Infirmary,
New York, NY.
Purpose: The aim of this study was to assess the educational impact of a novel
3-dimensional ON learning module for physicians in training.
Methods: Current medical school curricula rely on text book images of the optic nerve
(ON) for learning. The ON is a 3-dimensional structure that is best studied through
stereoscopic images. Medical students and non-ophthalmology residents participated
in the evaluation of a 3-dimensional ON learning module. The learning module
consisted of normal and glaucoma images included during a short course presentation.
All images were high resolution and obtained by simultaneous stereoscopic imaging
(Nidek 3-Dx camera, Gamagori, Japan, Nikon D1x 6.1 megapixel, Tokyo, Japan). Images
were mounted on View-Master (Fisher Price Inc. NY, USA) reels for stereoscopic
viewing by participants. To assess the educational value of the module, each participant
was asked to classify 25 ON images as normal or glaucoma before and again after
the course presentation. Correct classification scores, sensitivity and specificity were
calculated before and after the presentation.
Results: 15 physicians in training participated in the learning module. A total of 750
ON images were classified. The mean time for a training session was 14 minutes.
Correct classification improved in all participants (Mean 21%, SD 13%). Compared
to baseline sensitivity and specificity of correct classification significantly improved
after training. The results are summarized in the table.
Conclusions: In this pilot study the recognition of normal and glaucoma ON was
significantly improved after a single training with the 3-dimensional learning module.
This learning tool is practical and effective and may be incorporated into academic
curricula.
CR: A.S. Khouri, None; R.D. Fechtner, None; J.M. Liebmann, None.
Support: Research to Prevent Blindness, NY, NY
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
5356
Thursday, May 7, 11:15 AM - 1:00 PM Room 114 Paper Session Program Number Range: 5662 - 5668
529. Optic Neuropathy II Organizing Section: EY
5662 - 11:15AM
Identification and Characterization of a Novel 102 AA-Duplication in the
GTPase Domain of Opa1
5663 - 11:30AM
Light-Induced Melatonin Suppression in Mitochondrial Optic Neuropathies
N. Fuhrmann1, Y. Kamenisch2, B. Leo-Kottler3, B. Wissinger1, M.V. Alavi1. 1Centre
of Ophthalmology, Molecular Genetics Laboratory, Tuebingen, Germany;
2
Department of Dermatology, University Clinics Tuebingen, Tuebingen, Germany;
3
Department of Pathophysiology of Vision and Neuro-ophthalmology, University
Eye Hospital Tuebingen, Tuebingen, Germany.
C. La Morgia1, E. Sancisi1, A. Munarini2, V. Mantovani2, P. Barboni 3, R. Liguori1,
P. Montagna1, A.A. Sadun4, V. Carelli1. 1Department of Neurological Sciences,
University of Bologna, Bologna, Italy; 2Biomedical Centre Applied Research CRBA,
S.Orsola-Malpighi University Hospital, Bologna, Italy; 3D’Azeglio Ophtalmologic
Centre, Bologna, Italy; 4Doheny Eye Institute, University of Southern California,
Keck School of Medicine, Los Angeles, CA.
Purpose: Nowadays it is quite kerfuffle-free to differentiate autosomal dominant optic
atrophy (ADOA) from Leber’s hereditary optic neuropathy (LHON) due to the different
mode of inheritance and thanks to molecular genetic diagnostics. The Nosology of
these two hereditary optic neuropathies goes back as far as the 1950ies when W. Jaeger
put his hypothesis on the basis of the examination of a large German family.
Strikingly, no mutation has been identified in this family to date.
Methods: We used Multiplex Ligation Probe Amplification (MLPA), long distance PCR
and cDNA analyses to assess copy number variations in the Opa1 gene in this family.
Two patients underwent full ophthalmologic examinations and agreed to skin biopsies.
Therewith we investigated the consequences of this mutation on transcript and protein
level, assessed mitochondrial network organization and mtDNA integrity.
Results: Patients presented with a classical ADOA. MLPA analysis revealed a
duplication of the exons 7-9 which was confirmed by long distance PCR and cDNA
analysis. Segregation was verified in 53 available members of the updated pedigree
and we calculate a penetrance of 88%. The mutation results in an inframe duplication of
102 AA within the GTPase domain (p.L227_K328dup102). Qualitative and quantitative
Western blot analysis showed a reduction of all OPA1 isoforms when compaired to
actin. In regards to other mitochondrial proteins we see an increase of Opa1 to 200%.
In line we find an accumulation of the OPA1 precursor protein, but no additional bands
representing protein from the mutated allele. Quantitative cDNA analysis revealed
a reduction of the mutated allele whereas the overall OPA1 expression was elevated
more than 2 times. Fibroblasts present with significantly fragmented mitochondrial
network even when cultured under basal conditions.
Conclusions: More than 50 years past its first description we identified the disease
causing mutation in the family that initially laid the bases for the nosology of inherited
optic neuropathies. With the clinical, genetic and cell biological characterisation of
this family we span nearly one century of research in optic neuropathies giving new
insights into the disease mechanism of ADOA.
CR: N. Fuhrmann, None; Y. Kamenisch, None; B. Leo-Kottler, None; B. Wissinger,
None; M.V. Alavi, None.
Support: None
Purpose: To test the integrity of the retino-hypothalamic tract (RHT), originating
from the intrinsically photosensitive melanopsin-containing retinal ganglion cells
(ipRGCs), in mitochondrial optic neuropathies (ON), which selectively affect retinal
ganglion cells (RGCs). The non-rod/cone photoreceptors ipRGCs convey the detection
of light irradiance to the brain through the RHT, photoentraining circadian rhythms
and contributing to the pupillary light reflex (PLR).
Methods: Melatonin suppression test (MST) was performed in five Leber hereditary
optic neuropathy (LHON) and four dominant optic atrophy (DOA) patients, and in
nine gender and age-matched controls. A baseline and suppression night tests with
monochromatic (470 nm) blue light between 1:30 to 3:30 am were performed. Melatonin
was assayed by radioimmunoassay on plasma samples collected hourly from 12:30 pm
to 3:30 am. The suppression score was calculated comparing the suppression night
melatonin to the baseline night and statistics was run by One-way analysis of variance.
Clinical ON severity was determined by retinal nerve fiber layer thickness (RNFL)
as evaluated with Optical Coherence Tomography (OCT). All subjects completed
self-administered questionnaires (Pittsburgh sleep quality index, Morningness and
eveningness, Epworth Sleepiness Scale, Life quality index SF-36, Zung Anxiety and
Depression Scale).
Results: A significant suppression of melatonin plasma levels by light was observed
both in control subjects (67% ± 17%) and patients (LHON 65% ± 25% ; DOA 53% ± 33%).
The suppression score was not statistically different among groups. All patients had
severe optic atrophy and normal PLR. OCT evaluation documented an average RNFL
of 52 µm ± 9 in LHON and 59,3µm ±5,8 in DOA (controls 97,3µm±8,4). Self-administered
questionnaires showed statistical differences between controls and ON patients only
for SF-36 A and C items.
Conclusions: We demonstrate in both LHON and DOA a substantial preservation of
the circuit sustaining the photic input to the circadian system (RHT), as documented
by suppression of melatonin secretion by light and PLR preservation in these blind
patients.
CR: C. La Morgia, None; E. Sancisi, None; A. Munarini, None; V. Mantovani,
None; P. Barboni, None; R. Liguori, None; P. Montagna, None; A.A. Sadun, None; V.
Carelli, None.
Support: Telethon Grant GGP06233 to VC
5664 - 11:45AM
Retinal Nerve Fiber Layer Birefringence: Acute Reduction and Recovery in
Optic Neuritis
5665 - 12:00PM
Demonstration of Trans-Synaptic Retrograde Loss of Retinal Ganglion Cell
Loss Following Retrogeniculate Lesions in Humans Using Optical Coherence
Tomography(OCT)
M.J. Kupersmith1, Q. Zhou2, G. Mandel3, V. Atkinson4, S. Anderson 5, R. Kardon6.
1
Roosevelt Hospital and NYEE, New York, NY; 2Zeiss-Meditec, Inc, Sand
Diego, CA; 3Roosevelt Hospital, New York, NY; 4Zeiss Meditec, San Diego, CA;
5
Ophthalmology, Iowa University, Iowa City, IA; 6Ophthalmology, University of
Iowa and Veterans Hosptial, Iowa City, IA.
P. Jindahra1, A. Petrie2, G.T. Plant1. 1Neuro-Ophthalmology, The National Hospital
for Neurology and Neurosurgery, Queen square, London, United Kingdom;
2
Biostatistics Unit, Eastman Dental Institute, University College London, United
Kingdom.
Purpose: To determine if retinal nerve fiber layer (RNFL) birefringence, thought to be mostly
associated with axonal microtubule density, is affected at the onset of optic neuritis and if
it changes over 6 months.
Methods: 10 subjects had prospective good quality imaging of both eyes with OCT (Stratus)
for RNFL thickness and GDx (in ECC mode) for RNFL phase retardation at a mean 6.6 days
of vision loss and at 1, 3 & 6 months. We analyzed RNFL measurements divided into 12 clock
hour sectors at all visits. For each sector, we calculated percentage change in RNFL thickness
for OCT and in RNFL phase retardation for GDx compared to the corresponding sector of the
fellow unaffected eye. For each visit, the percentage birefringence change was calculated as
the percentage phase retardation change minus the percentage RNFL thickness change per
eye per sector and then averaged over the subjects. We evaluated the trends of mean overall
change (across sectors) based on RNFL thickness, retardation, and birefringence.
Results: The RNFL thickness was about 25% higher
and retardation was about 7% higher compared to
the fellow eye at baseline. Compared to the OCT
thickness, GDx retardation was more stable over 6
months, with approximately 9% cumulative
retardation reduction. (Figure shows change for OCT
and GDx over 6 months). The 6-month cumulative
amount of reduction in retardation (2%) was similar
to the 6-month OCT thickness loss (8.6%) when
compared to the fellow eye. The RNFL birefringence
was approximately -17.7% at onset and rebounded at 6 months.
Conclusions: The acute calculated drop in birefringence may result from reduction in
microtubule density due to intra-axonal swelling or microtubular alterations in response to
injury or from extracellular edema. Some of this calculated reduction seems to be recoverable.
Since OCT measures RNFL thickness and GDx measures RNFL retardation, combining the
two may reveal information that distinguishes recoverable tissue swelling from permanent
damage.
CR: M.J. Kupersmith, Teva Pharmaceutical, C; Q. Zhou, Zeiss Meditec, Inc, E; G. Mandel,
None; V. Atkinson, Zeiss Meditec, Inc, E; S. Anderson, None; R. Kardon, None.
Support: Pearle Vision Foundation, Teva Pharmaceutical
Purpose: Trans-synaptic retrograde loss of retinal ganglion cells in humans is well
established with congenital lesions but controversial with acquired pathology. The
aim of the study was to investigate whether thinning of the retinal nerve fibre layer
(RNFL) can be detected in such cases using OCT.
Methods:The thickness of the RNFL was measured in microns using Stratus OCT. There
were three patient groups all with occipital damage: cases of acquired homonymous
hemianopia (AHH; n=19); congenital homonymous hemianopia (CHH; n=7) and a
mixed group of both congenital and acquired homonymous quadrantanopia (CAHQ).
The results were compared with the right and the left eyes of 22 controls. A repeated
measures analysis of variance was performed to compare the mean values in the
different groups, separately for the eyes with temporal hemianopia (crossing fibre
defect eyes, CFD) and for the eyes with nasal hemianopia (non-crossing fibre defect
eyes, NonCFD).
Results: The mean RNFL in the CFD eyes was 79.8μ (SD=35.1μ) in AHH, 72.7μ (33.2μ)
in CHH, and 100.8μ (35.4μ) in the right eyes of the controls. The mean RNFL in nonCFD
eyes was 83μ (29.5μ) in AHH, 73.4μ (26μ) in CHH, and 101.4μ (36.6μ) in the left eyes of
the controls. In the CFD eyes, the mean RNFL was significantly greater in the control
group than in either of the hemianopia groups (p<0.001). In the NonCFD eyes, there
were significant differences between all three RNFL group means (p<0.001).
For the CAHQ group the mean RNFL in the CFD eyes was 88.2μ (35.1μ) and in the
NonCFD eyes was 89.2 μ (30.4μ). The mean RNFL was significantly greater in the
controls than in the quadrantanopia group (p=0.003) in both eyes.
The results were also analysed by dividing the peripapillary nerve fibre into 12
equal sectors around the circumference of the optic disc. These results demonstrated
that the RNFL thinning corresponded to the known trajectories of the crossing and
non-crossing fibres entering the optic disc and also to the retinal region of origin
corresponding to the visual field loss.
Conclusions: We have shown that trans-synaptic retrograde degeneration of retinal
ganglion cells occurs in both congenital and acquired post-geniculate lesions in
humans and that the magnitude of the loss is similar in both.
CR: P. Jindahra, None; A. Petrie, None; G.T. Plant, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
5662-5665
Thursday, May 7, 11:15 AM - 1:00 PM Room 114 Paper Session Program Number Range: 5662 - 5668
529. Optic Neuropathy II Organizing Section: EY
5666 - 12:15PM
Optic Nerve Compartment Syndrome. An Experimental Animal Model
5667 - 12:30PM
Quantitative Assessment of the Extracellular Matrix in the Optic Nerve Head
H.E. Killer1, M. Harlev2, U. Ziegler3, P. Groscurth 3, N.R. Miller4, P. Meyer5, S.
Dotan6, G. Jaggi7. 1Ophthalmology, Kantonsspital Aarau / University of Basel,
Aarau, Switzerland; 2Animal Research Center, Hadassah Hebrew-University
Hospital, Jerusalem, Israel; 3Anatomy, Institute of anatomy, University
of Zurich; Switzerland, Zürich, Switzerland; 4Ophthalmology, Wilmer
Ophthalmological Institute, Johns Hopkins Hospital, Baltimore USA, Baltimore,
MD; 5Ophthalmology, University of Basel, Eye Institute, Basel, Switzerland;
6
Ophthalmology, Hadassah Hebrew-University Hospital., Jerusalem, Israel;
7
Ophthalmology, Kantonsspital Aarau, Aarau, Switzerland.
D.J. Brown, A. Lay, L. Lam, S. Said, J. Jester, D.S. Minckler. The Gavin Herbert Eye
Institute, University of California, Irvine, Orange, CA.
Purpose: To report the results of experimental optic nerve compartmentation in sheep.
This study was performed according to the ARVO guidelines for animal research and
was approved by the local ethical committee
Methods: 4 female Dorper sheep were selected. Age was between 1-1.5 years, weight
between 30-35 kg. Orbitomy was performed under general anesthesia. The optic
nerve on one side was gently ligated with a silicone sling near the optic canal and
left in place in order to impair cerebrospinal fluid circulation. The optic nerves were
removed after three weeks and were worked up for histology.
Results: Light microscopy, transmission EM and scanning EM Light demonstrates
loss of axons in the periphery of the nerve at the site of the ligature. Behind the globe,
remote from the ligature, the axons loss is more pronounced, reaching in to the center
of the cross section. Transmission electron microscopy shows destruction of myelin
and axons while most of the cellular components of the optic nerve appear intact.
Conclusions: Light microscopy, transmission EM and scanning EM demonstrate
axon loss after experimental compartmenation of the optic nerve. The cross section
most involved is located distal to the ligation behind the globe. This pattern of axon
loss is unlikely to be caused by local trauma via the ligature. We suggest that statis
of CSF with accumulation of biologically active substances, such as L-PGDS my harm
the the unmyelinated axons and mitochondria in the bulbar region behind the globe,
causing anteriograde axon degeneration. Further studies including CSF analysis are
necessary to elucidate the pathophysiology of the axon loss pattern.
Reference: Killer HE, Jaggi G, Flammer J, Miller NR, Mironov A. Cerebrospinal fluid
dynamics between the intracranial -and the subarachnoid space of the optic nerve.
Is it always bidirectional? Brain 2007 129(4):1027-1030;
CR: H.E. Killer, None; M. Harlev, None; U. Ziegler, None; P. Groscurth, None; N.R.
Miller, None; P. Meyer, None; S. Dotan, None; G. Jaggi, None.
Support: Emilia Guggenheim-Schnurr-Stiftung
Purpose: Our goal was to quantitatively assess the structural components of collagen
and elastin in 3-dimensions across of the human optic nerve head (ONH).
Methods: Five pairs of eyes ranging in age from 59-84 were fixed in 4% paraformaldehyde
in PBS overnight at 4°C. The ONH was then removed, embedded in low melting point
agarose and then serially sectioned at 250 um using a Vibratome. Sections were
collected as a continuous series and nonlinear optical images of two photon excited
fluorescence (TPEF, elastin) and second harmonic generated signals (SHG, collagen)
were acquired using a Zeiss 510 Meta LSM and Chameleon femtosecond laser and a
10X 0.3 NA objective. For each section, a total of 24 overlapping multi-plane images
(512 x 512 pixels, 1.8 um lateral resolution) arranged in a grid (6 X4) were collected.
Images from each section were then concatenated into a single Z-stack mosaic of
3072x2048 pixels X 125 um, 8-bit multichannel image file. Mosaics were then processed
using a median filter (2x2 pixel) to reduce noise and normalized to match gray levels.
The Z-stacks were then demarcated into regions, a threshold established to exclude
background pixels and the percent area of included pixels recorded for each channel
using Metamorph software (Molecular Dynamics). Statistical analyses were performed
using Prism 4.0 (Graphpad).
Results: We demonstrate that, as expected, the SHG signal co localized with the
pattern of immunofluorescence achieved with an anti-collagen antibody. The TPEF
signal correlated well with the pattern of immunofluorescence achieved with an antielastin antibody. Using the SHG to indicate collagen and TPEF to indicate elastin, the
volume occupied by these matrix components varied considerably with position in
the ONH. Significantly, the proportion of elastin relative to collagen was markedly
higher in the prelaminar canal immediately anterior to the collagen beams of the
lamina. This enrichment in elastin content was also noted in the tissues immediately
adjacent to the canal wall.
Conclusions: The utilization of a multiphoton laser system allows one to obtain
detailed views of the structural components of the ONH that is optically based and
non-invasive. In addition, as the entire ONH can be assessed the data can be objectively
and quantitatively analyzed to determine the microscopic density of collagen and
elastin with the ONH.
CR: D.J. Brown, None; A. Lay, None; L. Lam, None; S. Said, None; J. Jester, None; D.S.
Minckler, None.
Support: NIH Grant EY16663, NIH Grant EY017959, Research to Prevent Blindness,
Discovery Fund for Eye Research
5668 - 12:45PM
Investigation of Fibril Ultrastructure in Optic Nerve by X-Ray Scattering
J.R. Lewis1, K.M. Meek 2, J.P.R.O. Orgel3. 1Ophthalmology, Biomed Engineering, The
Ohio State University, Columbus, OH; 2Biophysics Group, Optometry and Vision
Sciences, Cardiff University, Cardiff, United Kingdom; 3CSRRI, Dept. BCPS; Dept.
Biochemistry, Illinois Institute of Technology; Chicago Medical School, Chicago,
IL.
Purpose: Fibrillar species indicative of equatorially oriented collagen were identified
by wide-angle X-Ray diffraction in porcine optic nerve dissections providing proofof-concept for X-Ray analysis of human optic nerve tissue in situ.
Methods: Sections of porcine optic nerve tissue from paired, orientated eyes were fixed
in 4% paraformaldehyde and mounted in protective plastic. Medium- to wide-angle
diffraction at BMC-14 BioCARS (APS, Chicago, IL) with a 200 μm diameter, 0.9 Angstrom
wavelength beam and 40 cm detector distance was performed on serial sections along
the optic nerve. Fibrillar and molecular packing functions were measured from 1-D
slices of the X-Ray scattering patterns, after background subtraction and calibration
to hydrated rat tail tendon. The degree of anisotropy and relative abundances were
determined from the scattering intensity and distribution plots.
Results: Distinct X-Ray scattering patterns were observed. Equatorially oriented
fibrillar packing functions (and molecular packing functions) of the left and right eye
optic nerve sections corresponding to the region of unmyelinated axons and lamina
cribrosa were 39 Angstroms (15.25 Angstroms) and 41.5 Angstroms (15.25 Angstroms).
The fibrillar packing function increased and the molecular packing function decreased
thereafter in the distal myelinated sections. The fibrillar packing functions (and
molecular packing functions) measured sequentially in these sections distal to the
lamina cribrosa in the right eye were 46, 46, 44, and 44 Angstroms (and 11, 11, 10.2,
and 10.6 Angstroms). In comparison, the scleral molecular packing functions were
14.6 Angstroms and 14.5 Angstroms in samples from the left and right eyes.
Conclusions: Wide-angle X-Ray scattering to determine the fibril and molecular
packing functions and organization in the optic nerve and sclera is feasible as
demonstrated here. These data indicate that the fibrillar packing function is smaller
and the molecular packing function is larger at the level of the lamina cribrosa relative
to distal regions along the optic nerve. Mapping the fibrillar ultrastructure of the
optic nerve and surrounding sclera opens a new field of exploration. Ultrastructural
changes within these connective tissues can be examined with similar X-Ray scattering
techniques to correlate any changes occurring with vision loss and the effects of age,
race, disease.
CR: J.R. Lewis, None; K.M. Meek, None; J.P.R.O. Orgel, None.
Support: None
Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved.
For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes.
5666-5668