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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].