Download Extraocular muscles / Thyroid eye disease

ARVO 2015 Annual Meeting Abstracts
137 Extraocular muscles / Thyroid eye disease
Sunday, May 03, 2015 1:30 PM–3:15 PM
Exhibit Hall Poster Session
Program #/Board # Range: 556–572/B0014–B0030
Organizing Section: Eye Movements / Strabismus / Amblyopia /
Neuro-Ophthalmology
Contributing Section(s): Clinical/Epidemiologic Research
Program Number: 556 Poster Board Number: B0014
Presentation Time: 1:30 PM–3:15 PM
Novel Reverse Compressibility of Contracting Human Extraocular Muscles (EOMs) indicated By High Poisson Ratio (PR)
Lawrence H. Yoo, Robert A. Clark, Andrew Shin, Joseph L. Demer.
Ophthalmology, Jules Stein Eye Inst UCLA, Los Angeles, CA.
Purpose: A fundamental descriptor of the mechanical behavior of a
material is its PR, the ratio of transverse to axial strain, i.e., the ratio
of change in cross sectional area to change length during uniaxial
loading. A material having a PR <0.5 is said to be compressible.
Measurement of PR requires accurate 3-D determination of specimen
dimensions, typically by quantitative imaging during mechanical
loading. During passive, ex vivo tensile elongation, computed x-ray
tomography showed the PR of bovine EOM to be ~0.45 (Kim et al.,
BioMed. Res. International, 2013), but optical coherence tomography
demonstrated the PR of extraocular tendon to slightly exceed the
ideal incompressible value of 0.5 (Shin et al, ARVO, 2013). Since
the PR of contracting EOM is unknown, we used magnetic resonance
imaging (MRI) to determine the PR of all 4 rectus EOMs whose
axial dimensions change physiologically during horizontal & vertical
duction.
Methods: Surface coil MRI of 40 orbits of 20 normal adults was
performed at 312 micron resolution in ~20° target-controlled
horizontal and vertical eccentric gazes. Lengths were measured
in axial or quasi-sagittal images parallel to EOM long axes. Cross
sections were measured in quasi-coronal images perpendicular to
the long axes of each orbit. EOMs were outlined in coronal planes
to obtain area centroids cross sectional areas, and areal strain by
Green’s theorem. To correct for path curvature, centroids were
sequentially aligned to straighten each EOM for analysis. EOMs
were then discretized into elements 10-20 microns long. Changes in
longitudinal thickness of each element were determined to calculate
strain.
Results: Mean (±SD) PR values from discretized 3-D models for
the 20 superior, inferior, medial and lateral rectus muscles were
0.87±0.06, 0.79±0.03, 0.75±0.04 and 0.78±0.02 respectively.
Conclusions: PR values markedly exceeding the ideal compressible
value of 0.5 for contracting rectus EOMs imply that total volume
in the active contraction significantly exceeds that in relaxation, a
behavior termed reverse compressibility. Heretofore demonstrated
for tendons, reverse compressibility of EOMs would strongly impact
accuracy of finite element analysis simulations of EOM cooperative
biomechanics, and also provides a strong rationale for use of EOM
volume metrics as functional indices of contractility.
Commercial Relationships: Lawrence H. Yoo, None; Robert A.
Clark, None; Andrew Shin, None; Joseph L. Demer, None
Support: NIH EY08313
Program Number: 557 Poster Board Number: B0015
Presentation Time: 1:30 PM–3:15 PM
Comparison of myogenesis in human Extraocular muscle and
limb muscle in vitro
Hee-Young Choi1, Hye Shin Jeon1, Jeong Hyo Ahn1, Jin Hong
Shin2, Si Hyun Kim2. 1Ophthalmology, Pusan National University
hospital, Busan, Korea (the Republic of); 2Neurology, Pusan national
university Yangsan hospital, Yangsan, Korea (the Republic of).
Purpose: We investigated the myogenesis in human extraocular
muscle and compared with that in human limb muscle in vitro.
Methods: We obtained human extraocular muscle and limb muscle
during extraocular muscle surgery and limb muscle biopsy. Myoblast
was isolated and harvested until enough fraction of myoblast had
been achieved. Myogenesis was induced with F10 medium on
collagen-coated dish for 18 days. When myotube formation and
multiple nucleuses fusion were observed, cells were immunostained
with desmin (muscle specific protein) and myoD (determination of
the myogenic lineage) using each primary antibodies at day 10. We
evaluated morphologic characteristics of extraocular muscle and limb
muscle and compared extraocular muscle with limb muscle using
daily taken phase contrast photograph.
Results: Myoblasts fusion to form multinucleate myotube in both
human extraocular muscle and limb muscle primary culture started
at day 4. Immunocytochemistry for desmin and myoD were shown
positively stained at day 10 in both cells. Morphologic evaluation
revealed that extraocular muscle myoblasts were smaller and round
shape than limb muscle myoblasts at day 0. The process of myotube
formation and multinucleus fusion were similar time course in
extraocular muscle and limb muscle until day 7, but total area of
myotube formation and total number of nucleus in extraocular muscle
was smaller than limb muscle until day 10. However, total area of
myotube formation and total number of nucleus in limb muscle at day
2,4 was lower than day 10 (All, p<0.05) and total area of myotube
formation and total number of nucleus in extraocular muscle at day
3,5,7 was similar to day 10(All, p>0.05).
Conclusions: We have succeeded in primary culture of human
extraocular muscle myoblast and inducing myogenesis to form
multinucleated myotube in vitro. Our study reflects the differences
in myoblast and myogenesis between human extraocular muscle and
limb muscle
Commercial Relationships: Hee-Young Choi, None; Hye Shin
Jeon, None; Jeong Hyo Ahn, None; Jin Hong Shin, None; Si Hyun
Kim, None
Program Number: 558 Poster Board Number: B0016
Presentation Time: 1:30 PM–3:15 PM
Also Compartmentalized: Innervation of the Inferioir Oblique
(IO) Muscle in Primates
Alan Le1, 2, Vadims Poukens1, Joseph L. Demer1, 2. 1Ophthalmology,
University of California, Los Angeles, Los Angeles, CA;
2
Bioengineering, University of California, Los Angeles, Los Angeles,
CA.
Purpose: Innervation of the superior oblique muscle is separated into
minimally overlapping lateral and medial compartments in primates,
and superior and inferior compartments in non-primate mammalian
species. The horizontal rectus muscles are divided into superior and
inferior zones innervating non-overlapping sets of muscle fibers. We
explored the innervation pattern of the IO muscle and determined the
possibility of a compartmentalized model.
Methods: Whole orbits were obtained from two adult humans and
three rhesus monkeys. Each orbit was formalin fixed, embedded
in paraffin, coronally sectioned at 10 μm thickness, and stained
with Masson trichrome. In digital micrographs, oculomotor nerve
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
(CN3) branches were traced in serial sections using Photoshop
and reconstructed using ImageJ to create 3-D overlays of CN3
innervation in the IO muscle fibers.
Results: CN3 travels from the deep orbit and innervates at the
muscle belly of the IO. In both humans and monkeys, CN3 bifurcated
into two major branches prior to entering the IO muscle. Arborization
of the CN3 splits the IO muscle into two halves along its length.
One branch enters immediately as it reaches the muscle belly and
arborizes within muscle fibers from the posterior half. The other
branch straddles externally along the muscle belly before it penetrates
and arborizes in fibers of the anterior half.
Conclusions: Innervation of the IO muscle appears to follow a
compartmental model with the arborization dividing the muscle along
its length. Branching of the CN3 external to the muscle fibers allows
for independent movement between the two compartments. One
compartment could be more effective for elevation during adduction
while the other might have a greater effect on extorsion in primary
gaze.
Commercial Relationships: Alan Le, None; Vadims Poukens,
None; Joseph L. Demer, None
Support: NIH EY08313, Research to Prevent Blindness
Program Number: 559 Poster Board Number: B0017
Presentation Time: 1:30 PM–3:15 PM
Desmin in extraocular muscles
Fatima Pedrosa Domellof1, Kimmo Parkkonen1, Mona Lindström4,
Hanna Nord3, Jonas von Hoffsten3, Zhenlin Li2. 1Dept of Clinical
Sciences/Ophthalmology, UMEA University, Umea, Sweden;
2
UPMC Université Paris 6 - CNRS - INSERM, Institute of Biology
Paris-Seine, Paris, France; 3Umeå Centre for Molecular Medicine
(UCMM), Umea University, Umea, Sweden; 4Dept of Integrative
Medical Biology, Umea University, Umea, Sweden.
Purpose: To determine whether the lack of desmin reported in the
slow tonic muscle fibers of human extraocular muscles (EOMS) is
related to the presence of slow tonic myosin heavy chain (MyHC) or
multiple innervation or a feature specific to extraocular muscles and
to determine whether the EOMs are affected in a model of desmin
muscle dystrophy.
Methods: Immunohistochemistry was used to investigate the
presence of desmin in i) chicken anterior latissimus dorsi (ALD), a
muscle rich in slow tonic muscle fibers, ii) muscle spindles, whose
muscle fibers contain MyHC slow tonic and are multiply innervated
and iii) EOMs of rabbit, rat and zebra fish. The morphology, muscle
fiber size and muscle fiber integrity was evaluated in the EOMs of
desmin knockout mice and compared to that of wild type controls.
Results: Chicken ALD and muscle spindle fibers were labeled with
antibodies against desmin in similar patterns to those seen in control
skeletal muscle fibers. Muscle fibers containing slow tonic MyHC
in the EOMs of the different animals studied showed absence or
very low levels of expression of desmin, as previously observed in
the human EOMs. The EOMs of the desmin KO mice showed no
obvious signs of muscle dystrophy, in contrast to other highly used
skeletal muscles. More animals are under evaluation.
Conclusions: The very low levels of expression or lack of desmin
in the slow tonic muscle fibers was a feature typical for the EOMs
across species and not related to the presence of multiple innervation
or slow tonic MyHC, in other muscles. Preliminary data indicate that
the EOMs remain apparently unaffected in desmin muscle dystrophy.
Commercial Relationships: Fatima Pedrosa Domellof, None;
Kimmo Parkkonen, None; Mona Lindström, None; Hanna Nord,
None; Jonas von Hoffsten, None; Zhenlin Li, None
Support: Swedish Research Council (K2012-63x-20399-06-3),
County Council of Västerbotten (Cutting Edge Medical Research;
Central ALF), Stiftelsen Kronprinsessan Margaretas Arbetsnämnd för
Synskadade (KMA), The Kempe Foundation, The Swedish Society
of Medicine, The Medical Faculty, Umeå University
Program Number: 560 Poster Board Number: B0018
Presentation Time: 1:30 PM–3:15 PM
The Effect of Amniotic Membrane Grafting on healing and
wound strength in a Rabbit Model of Strabismus Surgery
Jeffrey B. Kennedy, Robert Enzenauer. Ophthalmology, University of
Colorado School of Medicine, Denver, CO.
Purpose: Postoperative scarring and adhesions after strabismus
surgery are common and may affect surgical outcomes. Amniotic
membrane grafts (AMG) have previously been shown to serve as
a successful platform for healing and to reduce scarring in cases
of ocular surface disease. Mixed results have been observed when
using AMG in conjunction with strabismus surgery. This study was
designed to evaluate the wound strength and histopathologic changes
on postoperative wound strength of amniotic membrane grafting in
conjunction with strabismus surgery using an in-vivo animal model.
Methods: Inferior rectus hang-back recession with processed
dehydrated amniotic membrane allograft (Ambiodry2, IOP Inc.,
Costa Mesa, CA) placed both between the sclera and the extraocular
muscle and between the extraocular muscle and the repositioned
conjunctiva was performed on 10 eyes of 10 New Zealand white
rabbits. Inferior rectus recession without amniotic membrane grafting
was performed on the alternate eye as a control. At postoperative
month 1, tensile strength of the muscle and overlying conjunctiva was
measured. Eyes were then enucleated and histopathologic analysis
performed to evaluate scarring and inflammatory response.
Results: Mean tensile strength of the AMG treated muscle and
conjunctiva was 441.4 +/- 274.4g and 640.3 +/-266.4g respectively.
The tensile strength of the control muscle and conjunctiva was
365.8 +/-199.8g and 595.2 +/- 315.3g respectively. No statistically
significant difference was detected based on ANOVA testing.
Histopathology demonstrated an increase in inflammatory infiltrate at
the muscle stump in AMG treated muscle.
Conclusions: There was no significant change in tensile strength
of the muscle insertion at post op month one in muscles treated
with amniotic membrane graft at the time of strabismus surgery.
Significant intra-animal variation in tensile strength was observed,
making a change difficult to detect. Further study is required to
determine the long term effect of amniotic membrane grafting on
post-operative scarring in strabismus surgery.
Commercial Relationships: Jeffrey B. Kennedy, None; Robert
Enzenauer, None
Program Number: 561 Poster Board Number: B0019
Presentation Time: 1:30 PM–3:15 PM
Growth factors regulate early events in adult zebrafish
extraocular muscle (EOM) regeneration
Alfonso Saera Vila, Alon Kahana. Ophthalmology and Visual
Sciences Department, University of Michigan, Ann Arbor, MI.
Purpose: Zebrafish are able to regenerate complex tissues, whereas
in mammals this ability is limited. Our laboratory uses EOMs as an
experimental model to study regeneration in sexually mature adult
zebrafish. Fibroblast growth factors (FGFs) have been shown to
promote tissue regeneration so we hypothesize that FGFs regulate
EOM regeneration in zebrafish.
Methods: A myectomy surgery that excised about 50% of the
lateral rectus (LR) muscle was performed to sexually mature adult
α-actin:EGFP zebrafish. At the end of the experiment, fish treated
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
with DMSO or the FGF receptor inhibitor SU5402 (17 μM) were
craniectomized and imaged. Muscle regeneration was calculated
using the uninjured contralateral muscle as a reference (100%).
Additionally, a-actin:EGFP or hsp70:dnfgfr1a-EGFP (a line that
expresses a dominant negative FGF receptor under control of the
heat shock protein 70 promoter) zebrafish were myectomized and
analyzed as described. Cell proliferation was analyzed injecting
fish with EdU to label cells in the S-phase of the cell cycle. The
involved cell signaling pathway was analyzed by testing the effect
of the MEK inhibitor U0126 (25 μM) in EOM regeneration and
proliferation as described. The activation of ERK was analyzed by
immunofluorescence and western blot.
Results: LR myectomy resulted in loss of abduction and, therefore,
the optokinetic response. Within 7 days, a new and functional LR
muscle regenerated. Both pharmacologic and genetic approaches
were used to analyze the role of FGFs. Treating myectomized fish
with the inhibitor SU5402 for 3 days reduced LR regeneration
from 70% to 58% (p<0.05). FGF role was confirmed using
hsp70:dnfgfr1a-EGFP in a time course experiment showing a
significant regeneration delay at 3 (13%, p<0.05), 5 (15%, p<0.05),
9 (36%, p<0.05), and 14 days (25%, p<0.01). Cell proliferation
was decreased in hsp70:dnfgfr1a-EGFP fish compared to WT fish
(19% and 27%, respectively; p<0.05). U0126 treated fish showed
a decrease in LR regeneration (71% vs 57%, p<0.05) and cell
proliferation (17% vs 9%, p<0.05). Immunofluorescence and western
blot confirmed the activation of ERK in the regenerating LR.
Conclusions: Our results show that FGFs, and most likely other
growth factors, play a significant role in the regeneration of EOMs in
zebrafish. Additional studies will be required to further uncover the
molecular mechanisms and target genes involved.
Commercial Relationships: Alfonso Saera Vila, None; Alon
Kahana, None
Support: NEI Grant R01EY022633
Program Number: 562 Poster Board Number: B0020
Presentation Time: 1:30 PM–3:15 PM
Medial rectus tendon elongation with bovine pericard
(Tutopatch®): an alternative to correct large horizontal squint
angles in graves’ orbitopathy
Monika Wipf. Augenklinik, Universitätsspital Basel, Basel,
Switzerland.
Purpose: Patients with Graves’ orbitopathy (GO) often present
large squint angles, especially following decompression surgery
of the medial orbital wall. These angles cannot be corrected with
conventional recession of the muscle alone. In this pilot study, we
report on four patients, where tendon elongation with Tutopatch®
was applied, to study the feasibility of this method, in particular the
dose- effect relationship.
Methods: We reviewed the charts of four patients with GO who
underwent bilateral recession of the medial rectus muscle and tendon
elongation with Tutopatch® within the last 5 years. At the time of
surgery, all patients had been stable for at least six months. Squint
angles were evaluated at distance and at near fixation preoperatively
as well as at postoperative week one, twelve and ≥52 (mean followup 49 months).
Results: Three patients had undergone previous orbital
decompression, one of whom had undergone previous bilateral 6mm
and 4.5mm, respectively, medial rectus recession with a residual
angle of 8°. The mean [range] preoperative angle was 38.8 [8- 68.7]°
at distance and 37.5 [6.9- 68.7]° at near fixation. This compared
to a mean postoperative angle of 1.1 [0- 2.9]° at distance and 5.1
[-2.0- 8.0]° at near fixation. Per muscle, the mean length of tendon
elongation was 6.8 [3.75- 13.5] mm with a mean total recession
of 9.8 [3.75- 17.5] mm. The mean dose- effect response was 1.83
[1.0-2.66] °/mm for the distance angle and 2 [1.4- 2.8] °/mm for the
near angle. All patients achieved a good functional outcome with
orthotropia, however in one patient following additional vertical
squint surgery.
Conclusions: We found the dose-effect response for medial rectus
recessions with Tutopatch® in GO to be comparable to reported
findings for dose-effect response for the inferior rectus muscle
recession with Tutopatch® (2°/mm), albeit with a slightly reduced
response at distance. This compares well to an effect of 1.99°/mm
for conventional inferior rectus recessions in GO as found in the
literature. However, in GO the dose-effect response for conventional
bilateral recessions of the medial rectus is considerably less (1.41.58°/mm).
Commercial Relationships: Monika Wipf, None
Program Number: 563 Poster Board Number: B0021
Presentation Time: 1:30 PM–3:15 PM
Clinical and Radiographic Features of Extraocular Muscle
Entrapment
Margaret L. Pfeiffer1, 2, Helen Merritt1, 2, Karina Richani1, 2, Margaret
E. Phillips1, 2. 1Ruiz Department of Ophthalmology and Visual
Science, The University of Texas Medical School at Houston,
Houston, TX; 2Robert Cizik Eye Clinic, Houston, TX.
Purpose: This is a retrospective chart review to investigate the
clinical and radiographic features of extraocular muscle entrapment
in patients presenting to the emergency department with orbital wall
fractures.
Methods: Patients who presented to the Memorial Hermann Hospital
emergency department, diagnosed with an acute orbital wall fracture
with extraocular muscle entrapment, and evaluated by ophthalmology
from January 2013 through November 2014 were included.
Clinical data were analyzed for the presence of symptoms and signs
associated with entrapment: diplopia, pain with eye movements,
nausea or vomiting, syncope, bradycardia, and restriction in
extraocular movements. Radiographic data were obtained including
interpretation of computed tomography (CT) by both ophthalmology
and radiology.
Results: Eight patients with an orbital wall fracture with extraocular
muscle entrapment confirmed by forced ductions were identified. The
median age was 22 (range: 9 to 72) years with 6 (75%) males and
4 (50%) white. Mechanisms of injury included 3 (37.5%) sportsrelated, 2 (25%) assault, 2 (25%) motor vehicle collision, and 1
(12.5%) fall. Diplopia and pain with eye movements were the most
common symptoms in 7 (87.5%) patients followed by nausea or
vomiting in 3 (37.5%). No patients had syncope. Two patients (25%)
were bradycardic with a pulse of less than 60 beats per minute; an
additional 2 had a pulse of 60. All had restricted extraocular motility.
Radiology accurately identified entrapment on CT in 3 (37.5%) cases
and interpreted an additional 3 (37.5%) as suspicious for entrapment.
Ophthalmology accurately identified entrapment on CT in 5 (62.5%)
cases and interpreted an additional 1 (12.5%) as suspicious. Overall,
ophthalmology correctly diagnosed entrapment in 5 (62.5%) cases
based on clinical and radiographic data. Three (37.5%) patients were
found to have entrapment on follow-up examination. In those patients
whose entrapment was not diagnosed, forced ductions were not
performed on initial evaluation.
Conclusions: Diplopia and pain with eye movements were the
most common symptoms of entrapment. Ophthalmology correctly
identified more cases of entrapment on CT than radiology, but 3 cases
were misdiagnosed by ophthalmology. We recommend high suspicion
for entrapment when both diplopia and pain with eye movements are
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
present and recommend performing forced ductions in all cases with
definite or suspicious imaging and clinical findings.
Commercial Relationships: Margaret L. Pfeiffer, None; Helen
Merritt, None; Karina Richani, None; Margaret E. Phillips, None
Support: National Eye Institute Vision Core Grant P30EY010608;
Challenge Grant from Research to Prevent Blindness; Hermann Eye
Fund
Program Number: 564 Poster Board Number: B0022
Presentation Time: 1:30 PM–3:15 PM
Quantitative Assessment of Ocular Motility Disturbance in
Orbital Blow-out Fractures
Jung Wook Lee1, EunHee Hong1, Moon sang won1, Heeyoon Cho1,
Sei yeul oh2, Yoon Duck Kim2, Han Woong Lim1. 1Ophthalmology,
Hanyang University Guri Hospital, Seoul, Korea (the Republic
of); 2Ophthalmology, Samsung Medical Center, Sungkyunkwan
University School of Medicine, Seoul, Korea (the Republic of).
Purpose: To measure the range of ocular motility using modified
limbus test (Fig 1) and to investigate the correlation with other factors
in patients with blow out fractures.
Methods: We enrolled 35 subjects with orbital blow-out fractures
who presented ocular motility disturbance. We measured the
maximum angle of ocular movements in the positions of restricted
motility of gaze using modified limbus test (Fig 2). We evaluated
number of points of contact of extraocular muscles to the fracture
edge (points of muscle contact) and the extent of blow out fracture
based on CT. The correlation between the degree of ocular motility
disturbance and the associated factors was estimated with linear
regression analysis.
Results: The mean of the angle of ocular motility disturbance
classified into grades 1,2,3, and 4 according to the clinical grage were
8.0±4.5°, 17.6±5.6°, 26.4±4.3°, and 40.2±8.3, respectively (P<0.001).
The angle of ocular motility disturbance showed significant
correlation with the clinical grading scale(R=0.730, P=0.015). The
extent of blow out fracture and the number of points of contact of
extraocular muscles to the fracture edge based on CT did not show
significant correlation with the angle of ocular motility disturbance
(R=0.250, P=0.127; R=0.453, P=0.072).
Conclusions: The modified limbus test using photographs in the
cardinal positions of gaze is an objective and reproducible tool
for quantifying ocular motility disturbance in the posttraumatic
evaluation of orbital blow-out fractures. The extent of blow out
fracture and number of points of contact of an extraocular muscle to
the fracture edge are not enough to predict posttraumatic limitation of
ocular movement in patients with blow out fractures in this study.
Figure 1. Image processing by Photoshop and Image J for quantitative
measurement of the ocular movement. A, Semitransparent image of
depression was overlapped with the primary position image using
Photoshop. B, The overlapping image was converted to identify the
margin of the limbus using Photoshop. C, Geometrical analysis with
Image J showing degrees of ocular rotation of the limbus.
Figure 2. An example of patient with blow-out fracture of right
inferior wall. Semitransparent image of elevation was overlapped
with the primary position image using Photoshop. The maximum
angle of elevation in right eye (the injured eye) was 22.6° which was
compared with 37.6° in left eye (the fellow eye).
Commercial Relationships: Jung Wook Lee, None; EunHee Hong,
None; Moon sang won, None; Heeyoon Cho, None; Sei yeul oh,
None; Yoon Duck Kim, None; Han Woong Lim, None
Program Number: 565 Poster Board Number: B0023
Presentation Time: 1:30 PM–3:15 PM
Retrieval of Slipped Muscles: Strategies and Impact
Ashley S. Ko1, Roy A. Cline2. 1Ophthalmology, University of Iowa,
Iowa City, IA; 2Ophthalmology, University of British Columbia,
Vancouver, BC, Canada.
Purpose: Slipped extraocular muscle (SEM) is an important and
serious complication of a strabismus surgery that is underdiagnosed,
often leading to intolerable symptoms and inappropriate reoperations
by misguided surgeons. Incidence and management data of SEM
is rare. While reference tables with projected corrective change per
millimeter of extraocular muscles correction with no previous surgery
is readily available, no such reference tables are available for SEMs.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
Additional data providing specific guidelines for SEM surgeries will
make a strong impact on surgical planning and outcome. The purpose
of this study was to formulate a nomogram for SEM strabismus
surgery, rendering an effective reference and strategy.
Methods: This retrospective chart review (13 years, January 2000
- April 2013) is a single centre study approved by University of
British Columbia Research Ethics Board. We looked at the type of
strabismus and the initial type of surgery performed. The orthoptics
data pre- and post- SEM correction surgery was analyzed. We also
gathered intraoperative data showing the position of the SEMs and
the amount corrected. The primary analysis involved determination
of how much correction of alignment was achieved (in prism diopters
[PD]) per millimetre of the eye muscle corrected. Other data included
gender, age at the time of initial surgery, visual acuity, timing of SEM
at presentation (recent <6 weeks; distant >6 weeks), and pathology
results.
Results: Total of 70 patient [26 (37.1%) male, 44 (62.9%) female]
were included in the study. Twelve (17.1%) cases were recent
(<6 weeks) and 58 (82.8%) cases were distant (>6 weeks) events.
Pseudotendon was identified clinically and/or pathologically in 67
(95.7%) cases. Effect of muscle advancement for slipped muscles
ranged between 0.6 and 9.1 PD/mm. The average effect was 3.92 PD/
mm. The median effect was 3.76 PD/mm.
Conclusions: The effect of SEM advancement can be very powerful
but also unpredictable and variable. Other factors to consider in
assessing each patient and performing the surgery are the quality
of muscle and the tightness of the antagonists. It is also likely that
sensory suppression and fusion play a major role in the outcome,
particularly in the secondary strabismic patients. It is important
to remember management and outcome of SEM surgery are
multifactorial and surgeons must be aware of the variabilities for each
case.
Clinical appearance of slipped muscle seen intraoperatively.
Commercial Relationships: Ashley S. Ko, None; Roy A. Cline,
None
Program Number: 566 Poster Board Number: B0024
Presentation Time: 1:30 PM–3:15 PM
The role of the MRTFA-SRF pathway in fibroblast to adipocyte
transdifferentiation in thyroid eye disease
Lilani Abeywickrama. NHS, London, United Kingdom.
Purpose: Thyroid eye disease (TED) is a progressive autoimmune
disease in which orbital fibroblasts transdifferentiate into adipocytes
and extraocular muscles undergo fibrosis. Myocardin-related
transcription factor A (MRTFA) is a co-factor of the transcription
factor Serum Response Factor (SRF). MRTFA binds to cytoplasmic
G-actin and translocates to the nucleus, upon stimulation of actin
polymerization. The actin-MRTF-SRF circuit regulates the expression
of target genes responsible for regulation of the actin cytoskeleton.
The downregulation of MRTFA causes a decrease in SRF activation,
which facilitates the conversion of fibroblasts to adipocytes. We
hypothesize the two phenotypes, seen in TED, are associated with
the SRF-MRTFA pathway. Our study focuses on how diseased cells
differ from control cells in terms of their MRTFA content and how
this relates to their propensity to differentiate into adipocytes.
Methods: This project was divided into 3 sections: 1) Oil Red O
staining to examine for the presence of adipocytes in TED cells; 2)
Immunostaining for MRTFA and IGFR1 in diseased cells; and finally
3) Western Blot Analysis to determine whether levels of specific
proteins (MRTFA, IGFR-1) are present in samples of affected cells.
Results: Our results demonstrated that fibroblasts underwent
adipocyte differentiation in vitro. We found a significantly high
nuclear-cytoplasmic ratio in diseased cells that implied greater
baseline activity of SRF-MRTFA in affected OF and our final
experiment identified similar quantities of protein MRTFA in both
control and TED cells.
Conclusions: In conclusion, SRF-MRTFA is linked with the process
of adipogenesis and a dual pathway is involved in the pathology of
TED.
Commercial Relationships: Lilani Abeywickrama, None
Program Number: 567 Poster Board Number: B0025
Presentation Time: 1:30 PM–3:15 PM
Systemic and Immune Thyroid Status in Hispanic Patients with
Recently Diagnosed Thyroid Eye Disease at the Conde Valenciana
Institute of Ophthalmology – Mexico City. A 7 year review
Alberto Carlos Abdala Figuerola, Sharon Ball-Burstein, Angel
Nava-Castaneda, Gerardo Graue-Moreno. Oftalmologia, Instituto
Oftalmologia Fundacion Conde Valenciana, Mexico DF, Mexico.
Purpose: To determine primary systemic and immune thyroid status
in hispanic patients debuting with thyroid eye disease (TED).
Methods: Retrospective, descriptive, transversal and comparative
study.
Thyroid status based on TSH levels, antithyroglobulin (TG Ab)
and antithyroperoxidase (TPO Ab) levels and clinical activity score
(CAS) were recorded for each patient at their first visit. Other
relevant clinical and demographic data were obtained from the
clinical records.
Results: 60 patients (36 women and 24 men) were eligible for this
study. 28 patients (47%) were hyperthyroid (17 on inflammatory/
active phase and 11 non-inflammatory/non active), 28 (47%) were
euthyroid (20 on active phase and 8 non-active) and only 4 (6.6%)
were hypothyroid (1 active and 3 non-active) at presentation.
From the active phase patients (n= 38), 9 had positive TPO Ab (23%)
while 11 had negative TPO Ab (28%), 7 had positive TG Ab (18%)
and 13 had negative TG Ab (34%). From the non-active patients (n=
22), 3 had positive TPO Ab (13%), 4 had negative TPO Ab (18%), 5
had positive TG Ab (22%) and 3 had negative TG Ab (13%).
A Spearman correlation test showed no evidence of significant
correlation between TSH and antibodies levels regarding
inflammatory activity as evaluated using the CAS classification.
Conclusions: A distinctive, non previously reported distribution
regarding endocrine and immune status was found in Hispanic TED
patients, which reveals that as high as 47% of primary TED patients
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
were euthyroid at the time of diagnosis. Interestingly, no correlation
was found between active TED and the immune status of the patients
regarding TPO and TG antibodies. Prospective studies with larger
samples are warranted to confirm these findings.
Commercial Relationships: Alberto Carlos Abdala Figuerola,
None; Sharon Ball-Burstein, None; Angel Nava-Castaneda, None;
Gerardo Graue-Moreno, None
Program Number: 568 Poster Board Number: B0026
Presentation Time: 1:30 PM–3:15 PM
Thyroid-associated ophthalmopathy: Epidemiologic
characteristics in a reference institution in Mexico City.
Paulina Nunez, Juan Carlos Serna-Ojeda, Alberto Abdala Figuerola,
Osiris Olvera Morales. Instituto de Oftalmologia Conde de
Valenciana, Mexico City, Mexico.
Purpose: Describe the epidemiological characteristics in Mexican
population with thyroid-associated ophthalmopathy and a comparison
with other series reported in literature.
Methods: A descriptive, retrospective and observational study was
performed in the Thyroid Clinic of the Department of oculoplastic
and orbital surgery in a reference institution through the revision
of clinical records. Patients of any age and gender with confirmed
diagnosis of thyroid-associated orbitopathy were included. We
excluded patients with high myopia and other causes of proptosis,
incomplete files, or patients with a history of any ocular surgery
related to thyroid eye disease. The variables included in the study
were sex, age, smoking history, thyroid status, exophthalmometry
and presence of clinical signs like eyelid retraction at the time of first
consultation through a thyroid profile. A descriptive investigation
was performed for the variables according to its distribution and the
intergroup analysis was done with Student’s t test.
Results: A total of 241 patients, 187 (77.6%) females and 54
(22.4%) males were included. The 40 to 59 years interval was the
predominant group (56.4%) for the presentation of the disease. In
relation to smoking history, 42.3% of patients reported a positive
history for smoking. The thyroid status that predominated at the time
of diagnosis of thyroid-associated ophthalmopathy was euthyroidism
with 47.3%. The exophthalmometry had a media of 19.8mm. The
most common clinical sign was eyelid retraction in 83.4% of the
patients.
Conclusions: Variables such as age, sex and eyelid retraction
presented in similar proportions to those reported in studies
conducted in different countries and ethnic groups. In Mexican
population the initial thyroid hormone status is variable and patients
may present with eye manifestations despite of having a profile in
normal ranges.
Commercial Relationships: Paulina Nunez, None; Juan Carlos
Serna-Ojeda, None; Alberto Abdala Figuerola, None; Osiris
Olvera Morales, None
Program Number: 569 Poster Board Number: B0027
Presentation Time: 1:30 PM–3:15 PM
Effect of Orbital Decompression on Corneal Topography in
patients with thyroid ophthalmopathy
Su Ah Kim1, Kui Dong Kang2, Ji Sun Paik1, Su Kyung Jung1, Suk-Woo
Yang1. 1Ophthalmology, The Catholic University of Korea, Seoul St.
Mary’s Hospital, Seoul, Korea (the Republic of); 2Ophthalmology,
Incheon St. Mary’s Hospital, The Catholic University of Korea,
Incheon, Korea (the Republic of).
Purpose: This study was performed to evaluate the changes of
corneal astigmatism in patients undergoing orbital decompression
surgery.
Methods: This retrospective, nonrandomized comparative study
comprised 42 eyes from 21 patients with thyroid ophthalmolpathy
who underwent orbital decompression surgery between September
2011 and September 2014. The 42 eyes were divided into three
groups: control (9 eyes), two wall decompression (24 eyes), and
three wall decompression (8 eyes). Control was defined as the
contralateral eyes of 9 patients who underwent orbital decompression
surgery only in one eye. Corneal topography (Orbscan II), Hertel
exophthalmometry, and intraocular pressure were measured at 1
month before and 3 months after surgery. Corneal topographic
parameters analyzed were the total astigmatism(TA), steep axis(SA),
central corneal thickness(CCT), and anterior chamber depth(ACD).
Results: Exophthalmometry values and intraocular pressure were
significantly decreased after the decompression surgery. The change
(the absolute value (|x|) of the difference) of astigmatism at 3mm
zone was significantly different between the decompression group
and the control (P = .0250). There was also significant change of the
steepest axis at 3mm zone between the decompression group and the
control (P = .0331). An analysis of relevant changes in astigmatism
showed that there is a dominant tendency of incyclotorsion of the
steepest axis in eyes which underwent decompression surgery.
Using Astig PLOTTM, the mean surgically induced astigmatism
(SIA) was 0.21±0.88D with the axis of 46±22° which suggest that
decompression surgery did change the corneal shape and induced
incyclotorion of the steepest axis.
Conclusions: There is a significant change in corneal astigmatism
after orbital decompression surgery and this change is sufficient to
affect the optical function of the cornea. Surgeons and patients should
be aware of these changes.
Commercial Relationships: Su Ah Kim, None; Kui Dong Kang,
None; Ji Sun Paik, None; Su Kyung Jung, None; Suk-Woo Yang,
None
Program Number: 570 Poster Board Number: B0028
Presentation Time: 1:30 PM–3:15 PM
Surgical treatment of proptosis secondary to Thyroid Eye Disease
without a cutaneous incision
Paul Petrakos1, Benjamin M. Levine1, Ashutosh Kacker2, Aaron
Pearlman2, Gary J. Lelli1. 1Ophthalmology, Weill Cornell Medical
College, New York, NY; 2Otolaryngology, Weill Cornell Medical
College, New York, NY.
Purpose: To evaluate the improvement of proptosis secondary to
Thyroid Eye Disease in patients treated surgically without the use of
a cutaneous incision.
Methods: A retrospective study of 24 eyes of 13 patients who were
surgically treated for proptosis secondary to Thyroid Eye Disease
(TED) without the use of a cutaneous incision. Patients included
in the study underwent either (1) bony decompression (endoscopic
medial orbital wall and orbital floor decompression with removal
of bone with or without fat), or (2) orbital fat decompression. Pre-
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
operative and post-operative Hertel measurements, as well as patient
satisfaction, were documented to assess surgical outcomes.
Results:
The average pre-operative Hertel measurement for all eyes was
24mm (SD 3.75), 25mm (SD 4.96) for the bone decompression group
(n=8), and 23mm (SD 1.69) for the fat decompression group (n=8).
The average post-operative Hertel measurement for all eyes was
19.6mm (SD 1.08), 19.8mm (SD 1.39) for the bone decompression
group (n=8), and 19.4mm (SD 0.69) for the fat decompression group
(n=8). The mean post-operative improvement in Hertel measurement
for all patients regardless of surgical modality was 4.6mm (SD 3.03)
with a two-tailed p value <0.0001. For the eyes that underwent
bone decompression improvement was 5.3mm (SD 3.65), while fat
decompression was 3.9mm (SD 2.28). The difference in proptosis
between the two different surgical groups was not statistically
significant (p=0.373). Hertel pre and post-operative measurements
were not recorded for 8 patients. Subjectively all patients (100%)
reported satisfaction with their post-operative outcomes. No postoperative infections or inadequate decompression were seen in
any cases. One patient required subsequent strabismus surgery for
diplopia, but had a history of strabismus and patching as a child.
Conclusions: Orbital decompression with removal of bone or
orbital fat decompression without the use of a cutaneous incision
is an efficacious and safe modality for the treatment of proptosis in
TED patients. There was a statistically significant improvement in
proptosis for all patients treated surgically. The difference between
the two surgical groups was not statistically significant. Employing
this modality in aesthetically-minded patients who are concerned
over the potential for a cutaneous scar may be advantageous.
Commercial Relationships: Paul Petrakos, None; Benjamin M.
Levine, None; Ashutosh Kacker, None; Aaron Pearlman, None;
Gary J. Lelli, None
Program Number: 571 Poster Board Number: B0029
Presentation Time: 1:30 PM–3:15 PM
Comparative study of ganglion cell-inner plexiform layer
(GCIP) and circumpapillary retinal nerve fiber layer (cpRNFL)
measurements by spectral-domain optical coherence tomography
for the detection of dysthyroid optic neuropathy
Wai U IAO, Kam-lung, Kelvin K. Chong. The Chinese University of
Hong Kong, Hong Kong, Hong Kong.
Purpose: To compare ganglion cell-inner plexiform layer (GCIP) and
circumpapillary retinal nerve fiber layer (cpRNFL) measurements in
thyroid associated orbitopathy (TAO) eyes with no, suspected and
definite dysthyroid optic neuropathy (DON).
Methods: Retrospective, cross-sectional study. Thirty-four TAO
eyes, including 10 eyes with no DON, 7 with suspected DON and
17 with definite DON were analyzed. All subjects received complete
ophthalmic evaluation, visual field (VF) examination with the
Humphrey Visual Field Analyzer and optical coherence tomography
(OCT) imaging in the macular and circumpapillary regions with
Cirrus HD-OCT. Mann-Whitney U tests were used to compare GCIP
and cpRNFL thicknesses among the three groups with bootstrap
resampling with 10000 replications using one eye from each subject.
Results: The median GCIP thickness was 83.46 mm for the group
with no DON, 81.30 mm for the group with suspected DON, and
78.02 mm for the group with definite DON. Reduced GCIP thickness
was observed in the definite DON group (p < 0.017, after Bonferroni
adjustments) when compared with the groups with no or suspected
DON. The comparison of cpRNFL thickness among different groups
showed no significant differences.
Conclusions: In patients with TAO, GCIP thickness with SD-OCT is
a better objective test than cpRNFL for detection of optic neuropathy.
Commercial Relationships: Wai U IAO, None; Kam-lung, Kelvin
K. Chong, None
Program Number: 572 Poster Board Number: B0030
Presentation Time: 1:30 PM–3:15 PM
Outcomes of Surgical Management of Thyroid Eye Disease: A
Single-Centre Retrospective Study
Jia Quan Chaung1, 2, Raghuraj Hegde1, Shantha Amrith1, Inez Wong1,
Siew Shuen Chao1, Gangadhara Sundar1. 1Ophthalmology, National
University Hospital, Singapore, Singapore; 2National University of
Singapore, Singapore, Singapore.
Purpose: To study the outcomes of surgical management of thyroid
eye disease (TED) in a South East Asian Population
Methods: Retrospective single-centre case series of all TED patients
requiring surgery from Nov 2002 to August 2014 by 2 Oculoplastic
surgeons. Data recorded included demographic data, pre-operative
and post-operative visual acuity and exophthalmometry for orbital
decompression; ocular alignments, revision surgeries for both
strabismus and eyelid retraction.
Results: Of the 336 TED patients seen, 57 patients underwent
surgery, 24 male (42.1%) and 33 female (57.9%). Ethnicity: Chinese
(73.7%), Malay (14.0%), Indian (5.3%), Others (7.0%). Mean age
was 44.2 years (Range 2-81). Surgical indications: Eyelid retraction
(52.6%), proptosis (45.7%), cosmesis (33.3%), Exposure Keratopathy
(10.5%), Compressive optic neuropathy (8.8%). Surgical procedures
included orbital decompression (54.4%), eyelid surgery (52.6%)
and strabismus surgery (24.6%). 60 orbits of 31 patients were
decompressed: 2-wall (36.7%), pure fat (23.3%) 3-wall (21.7%),
1-wall (18.3%). Medial wall access – retrocaruncular (61.1%)
or endonasal (38.9%). Most 2-wall decompressions involved
balanced lateral and medial walls (72.7%). The mean reduction in
exophthalmometry was 4.5mm (Range -2 - 17) with an improvement
of at least one Snellen line in 62.9% of patients. Rate of induced
strabismus was 3.2%. Strabismus surgery was performed on 23 eyes
of 14 patients of which 1 required surgical revision. Medial rectus
was most frequently recessed (34.6%). Diplopia was resolved in
85.7%. Most eyelid surgeries involved the upper lid (55.1%) and
Muller’s muscle resection (69.7%). Mean reduction of MRD by
1.5mm. Satisfaction with appearance was achieved in 89.7% while
20.7% of eyelid surgeries required revision. Other eyelid procedures
performed included entropion surgery, permanent tarsorrhaphy,
epiblephron repair, ptosis repair and blepharoplasty.
Conclusions: Surgery for TED is not uncommon in our SouthEast Asian population. Orbital decompression was efficacious in
reducing proptosis and improving visual acuity. Complications
observed included diplopia and paresthesia. Strabismus and eyelid
surgery were used to effectively reduce diplopia and lid retraction
respectively. However, they may require revision surgeries to achieve
adequate correction.
Commercial Relationships: Jia Quan Chaung, None; Raghuraj
Hegde, None; Shantha Amrith, None; Inez Wong, None; Siew
Shuen Chao, None; Gangadhara Sundar, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].