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Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706 127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY 646 - D686 The Microrna Expression Profile of Rodent Extraocular Muscles 647 - D687 Quasi-linear Viscoelastic Behavior of Bovine Extra-ocular Muscles C.A. McMullen, F.H. Andrade. Physiology, University of Kentucky, Lexington, KY. L.H. Yoo1A,2, H. Kim1A, V. Gupta1B,1A, J.L. Demer2,1B. AMechanical Engineering, B Biomedical Engineering, 1UCLA, Los Angeles, CA; 2Ophthalmology, UCLA, Jules Stein Eye Inst/Los Angeles, CA. Purpose: The extraocular muscles (EOMs) represent an extreme example of skeletal muscle specialization. It is not surprising that transcriptional and biochemical studies of these muscles have identified many genes and proteins differentially expressed in EOMs compared to limb skeletal muscles. MicroRNAs (miRNAs) are small noncoding RNAs (21 to 26 nucleotides) that regulate gene expression by inhibiting mRNA translation or promoting mRNA degradation. Some miRNAs are tissue-specific and may influence the adult tissue phenotype. In this study, we tested the hypothesis that EOMs would have a unique miRNA expression profile that would include a combination of muscle-specific miRNAs. Methods: We isolated EOMs and gastrocnemius muscles from adult male SpragueDawley rats for expression profiling using miRNA microarrays, real-time quantitative PCR, and northern blots. Results: A total of 223 miRNAs were present in all muscle samples (out of 636 miRNAs). Fourteen miRNAs were more abundant in EOMs compared to gastrocnemius, and five were less abundant. Surprisingly, miR-206, previously demonstrated to be enriched in skeletal muscle, was significantly less abundant in EOM. miRNAs more abundant in EOM were miR-133a/b which have been found in skeletal muscle and heart. miRNAs found in brain were also increased in EOM: miR-24 and miR-30c. Ubiquitously expressed miRNAs, miR-143and and miR-320 were also upregulated in EOM. Conclusions: The results support our initial hypothesis that EOMs have a specific miRNA expression profile, significantly different from that of a limb skeletal muscle. These EOM-enriched miRNAs may represent a hitherto unrecognized regulatory influence on the phenotype of these muscles. Supported by NEI EY12998 CR: C.A. McMullen, None; F.H. Andrade, None. Support: NEI EY12998 648 - D688 Identification of the Unique Extraocular Muscle (EOM) ‘microRNAome’ Purpose: There has been no prior comprehensive analytical model of the nonlinear viscoelastic stress-strain behavior of extraocular muscles (EOMs). The present study describes the nonlinear, history-dependent viscoelastic properties and elastic stressstrain relationship of the EOMs using a quasi-linear viscoelastic (QLV) model. Methods: From each of the six oculorotary EOMs obtained fresh from a local abattoir, longitudinally oriented specimens were taken from different regions and subjected to uniaxial tensile, relaxation, and cyclic loading testing using an automated load cell under temperature and humidity control. Twelve samples were subjected to uniaxial tensile loading with 1.7%/s strain rate until failure to characterize elastic function within the mechanical model. Sixteen specimens were subjected to relaxation studies over 1,500 seconds to describe time-dependent viscoelastic behavior exhibited by EOMs. Cyclic loading was performed to validate predictions of the QLV model characterized from uniaxial tensile loading and relaxation data. Results: Uniform and highly repeatable stress-strain behavior was observed for 12 specimens extracted from various regions of all EOMs. Since the results from tensile tests and relaxation tests of all six EOMs were similar, mechanical properties for each of the six EOMs were assumed to be same. Results from 16 different relaxation trials illustrated that most stress relaxation occurred during the first 30-60s for 30% extension. Elastic and reduced relaxation functions were fit (nonlinear least square fit) to the data, from which a QLV model was assembled and compared with cyclic loading data. Predictions of the QLV model agreed with observed peak cyclic loading stress values to within 8% for all specimens and conditions. Conclusions: Close agreement between the QLV model and both relaxation and cyclic loading data validates model quantification of EOM mechanical properties, and will permit development of accurate overall models of mechanics of ocular motility and strabismus. CR: L.H. Yoo, None; H. Kim, None; V. Gupta, None; J.L. Demer, None. Support: NIH Grant EY08313, NIH Grant EY00331 649 - D689 Applying Computer Aided Visualization Techniques to Extra Ocular Muscle and Eye MRI U. Zeiger, T.S. Khurana. Physiology and Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, PA. Purpose: The EOMs are a unique group of muscles that are anatomically and physiologically distinct from other skeletal muscles. Strikingly, EOMs show differential susceptibility to disease, exemplified by their preferential sparing in Duchenne’s Muscular Dystrophy (DMD). Previously, we and others have shown that EOMs have a unique transcriptome and proteome. In this study we investigated the expression pattern of microRNAs (miRNAs) at the whole genome level, as they may play a role in generating the unique EOM allotype. Methods: We used microRNA microarray chips (LCSciences) covering the sequences of miRBase 10.0 to define the microRNAome of normal mouse EOM and limb muscle (TA-tibialis anterior). Data of four independent chips were analysed using background substraction, normalization and statistics. Online databases, such as miRBase and TargetScan were used to identify potential miRNA-target pairs. Results: 74 miRNAs were found to be differentially regulated based on a p-value of < 0.05 (t-test); 43 miRNAs were up-regulated and 31 miRNAs were down-regulated. Bioinformatic tools and databases were used to integrate the results with our previous transcriptomic and proteomic profiling data. Interestingly, miR-155 which we found to be down-regulated in EOM, has recently been shown to be up-regulated in many primary muscular disorders, including DMD (Eisenberg et al. PNAS 2007). Conclusions: In conclusion, our definition of the distinct and unique EOM microRNAome complements existing data about the molecular make-up of EOM, which will help to explain their differential sensitivity to disease and may assist in development of therapeutic strategies. CR: U. Zeiger, None; T.S. Khurana, None. Support: NIH Grant EY013862 A.M. Palmowski-Wolfe1A, C. Kober2, I. Berg1B, C. Buitrago-Téllez3, C. Kunz1C, E.W. Radü1D, S. Wetzel1D. ADepartment of Ophthalmology, BDept. of Cranio-Maxillofacial Surgery, CDepartment of Cranio-Maxillofacial Surgery, DDepartment of Neuroradiology, 1University of Basel, Basel, Switzerland; 2Faculty of Life Science, Germany, HAW Hamburg, Hamburg, Germany; 3Radiological Center Aarau, Spital Zofingen AG, Zofingen, Switzerland. Purpose: At ARVO 2008 we had shown computer aided visualization techniques (CAVT) applied to oculodynamic MRIs of the orbit. Within the extra ocular muscles (EOM) a devision was seen that was discussed as possibly relating to the obital and the bulbar layer of the EOM. The purpose of this study is to further improve information on EOM structure and the eye in an integrated MRI-based approach. Methods: A threefold strategy was followed. First, a post mortem MRI of a control subject was analyzed (1.5T, T1 weighted image sequence, 0.6mm layer thickness). 2nd, we analyzed a 1.5T MRI, done with the Gadolinium based contrast agent Dotarem®, that was obtained in a tumor patient for evaluation of his underlying disease. 3rd, the resulting images were compared to those of a living control (1.5 T) whose oculodynamic MRI movies we presented last year. To enhance visibility of the orbital structures, special adapted CAVT procedures based on direct volume rendering were applied to all MRI scans. Results: For all three approaches, the horizontal and vertical EOM could be clearly identified. Also, for all approaches, these EOM revealed a two layered structure, possibly related to the orbital and bulbar layer of the EOM, with some intermediate tissue in between. In the Dotarem ® MRI, contrast was enhanced in both the presumed ocular and the presumed bulbar layer of the EOM, but the intermediate zone was spared, indicating the absence of vascular structures. The enhanced contrast based on CAVT techniques facilitated identification of sclera, periorbita and muscular structures. Due to high resolution and image quality of the post mortem MRI, highly detailed 3D-reconstruction of the orbital anatomy was possible that allowed better visualization of the oblique muscles and virtual ‘turning’ of the eye in all directions. In addition, the lens including its attachment to the ciliary fibers could be shown. Conclusions: Distribution of the contrast medium, Dotarem, in the EOM supports our previous thesis that 2 layers of the EOM can be shown. We postulate, that these relate to the orbital and the bulbar layer of the EOM. While 3D-reconstruction of the eye and its EOM could be greatly improved, differentiation within the connective tissue at the EOM muscle insertion to the sclera is still subject to future work. CR: A.M. Palmowski-Wolfe, None; C. Kober, None; I. Berg, None; C. BuitragoTéllez, None; C. Kunz, None; E.W. Radü, None; S. Wetzel, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 646-649 Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706 127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY 650 - D690 Treatment of Dysthyroid Ophthalmopathy With Superior Eye Lid Injection of Triamcinolone 651 - D691 Clinical and Mri Features in Patients With Dysthyroid Optic Neuropathy A. Kozaki, T. Inoue, N. Komoto, R. Inoue, Y. Inoue. Ophthalmology, Olympia Eye Hospital, Tokyo, Japan. N. Komoto, A. Kozaki, R. Inoue, T. Inoue, T. Maeda, T. Inoue, Y. Inoue. Olympia Eye Hospital, Shibuya-ku, Japan. Purpose: This study was conducted to assess the therapeutic efficacy of triamcinoline injection therapy on lid retraction and swelling associated with dysthyroid ophthalmopathy. Methods: The subjects of this study consisted of 29 eyes of 21 cases of dysthyroid ophthalmopathy that were injected with triamcinoline (40mg) via the conjunctiva of the upper eyelid for treatment of lid retraction and swelling and then monitored for three months or more. The subjects consisted of 5 eyes of 3 men and 24 eyes of 18 women. The average age was 43 years. The proptosis as measured by MRI had an average value of 18.9 mm. To determine side effects of the treatments, palpebral fissure height, degree of swelling, sizes of the superior rectus muscle (SR) and levator palpebrae superioris muscle (levator) as determined by MRI were evaluated after treatment and compared to the respective value before treatment. Efficacy was evaluated by defining improvement of palpebral fissure height of 1 mm or more as indicating efficacy against lid retraction and evaluating swelling on the basis of photographs of the external eye at three months after treatment. Results: Treatment for lid retraction was performed on 20 eyes while treatment for swelling was performed on 22 eyes (some eyes underwent treatment for both). The average palpebral fissure height was 9.6 mm before treatment and 8.7 mm after treatment, demonstrating a significant decrease (P<0.05). There were 11 eyes (55%) in which treatment was effective for lid retraction and 19 eyes (86%) in which treatment was effective for swelling. Although there were no changes observed in surface area of the SR before and after treatment, that of the levator decreased significantly (P<0.05). T2-SIR, which is an indicator of inflammatory activity of the extraocular muscle, was significantly decreased after treatment in both cases (P<0.05). Side effects consisted of 1 eye exhibiting ocular hypertension (Max.27mmHg) that occurred 3.5 months after the injection. Conclusions: Although triamcinoline injection therapy demonstrated somewhat low efficacy against lid retraction, it was thought to be extremely effective against eyelid swelling. CR: N. Komoto, None; A. Kozaki, None; R. Inoue, None; T. Inoue, None; T. Maeda, None; T. Inoue, None; Y. Inoue, None. Support: None Purpose: To define clinical background factors such as thyroid function, systemic and ocular history, and Magnetic Resonance Imaging (MRI) features in patients with dysthyroid optic neuropathy (DON). Methods: The study involved 42 consecutive DON patients (male: 17, female: 25) of which 72 eyes were examined. All patients underwent visual field and MRI examination. Mean age was 58 years old. Results: Patients with thyroid dysfunction included Graves’ disease (40 patients), and Hashimoto disease (2 patients). Of those with Graves’ disease 2 (5%) were pregnant females and 4 (10%) had undergone radioiodine treatment. Thyrotropin receptor antibodies (TRAb) and thyroid stimulating antibodies (TSAb) were found to be present in 31 of 37 and 38 of 38 patients, respectively. In past history, 6 patients had diabetes and 4 had hepatitis. Twenty-seven patients (64%) were smokers or ex-smokers. In ophthalmic examination the proptosis ranged from 12 to 24 mm (average 18.1 mm). Best corrected visual acuity was less than 20/200 in 15 eyes and 20/25 or better in 19 eyes. All eyes had visual fields abnormalities and reduced critical flicker fusion frequency (CFF). Optic disc appearance was normal in 36 eyes (50%) with DON. Orbital imaging using MRI showed apical muscle crowding in all eyes. Forty five eyes had enlargement of 4 rectus muscles, 21 had enlargement of 3 rectus muscles, 5 had enlargement of 2 rectus muscles, and one only involved the superior rectus. In T2 enhanced MRI, 25 of 67 eyes had superior ophthalmic vein enhanced. Conclusions: Patients with DON did not show severe proptosis or abnormal optic disc features. TSAb should be tested in equivocal DO patients as this was found to be present in all patients. Radiological evidence of optic nerve compression is the most useful clinical features in DON, as all eyes showed involvement of at least one rectus muscle. CR: A. Kozaki, None; T. Inoue, None; N. Komoto, None; R. Inoue, None; Y. Inoue, None. Support: None 652 - D692 Changes of Extraocular Muscle and Orbital Fat After Cervical Sympathectomy (Iatrogenic Horner’s Syndrome) in Rats 653 - D693 Length and Connectivity of Global Layer (GL) Fibers in Primate Superior Oblique (SO) Muscle I.-Y. Chung1, S. Seo1, J. Park1, N. Lee1, H. Kim2, J. Song1. 1Ophthalmology, Gyeongsang National University, Jinju, Republic of Korea; 2Ophthalmology, Inje University, Pusan, Republic of Korea. J.L. Demer1, V. Poukens1, H. Ying2A, X. Shan2B, J. Tian2B, D.S. Zee2B. 1Ophthalmology, Jules Stein Eye Institute, Los Angeles, CA; AOphthalmology, BNeurology, 2Johns Hopkins University, Baltimore, MD. Purpose: To investigate whether cervical sympathectomy (iatrogenic Horner’s syndrome) induces the morphological changes of extraocular muscles and orbital fat in rats. Methods: Unilateral cervical ganglionectomy was done on Sprague-Dawley rats (n=9). Sympathetic innervation to the eye was destroyed by surgical removal of the right superior cervical ganglion (superior cervical ganglionectomy; SCGx). The signs of iatrogenic Horner’s syndrome in these rats included right ptosis and enophthalmos. After 8 weeks, we extracted bilateral extraocular muscles and orbital fat from rats. The changes of each tissue were observed and compared using both light and electron microscopy. Results: After cervical ganglionectomy, there were no morphological changes between the control (left) and the experimental (right) orbital fat tissue in rats. However, the right extraocular muscle (EOM) fibers showed a smaller diameter than the left under light microscopy. We observed that the number and size of mitochondria were decreased in the right EOM tissue compared to the left using electron microscopy. Conclusions: EOM fiber diameter, number, and size of the mitochondria were significantly attenuated after cervical ganglionectomy in rats. Our data suggest that extraocular muscle atrophy and changes of mitochondria in EOM may take part in understanding enophthalmos after cervical sympathectomy. CR: I.-Y. Chung, None; S. Seo, None; J. Park, None; N. Lee, None; H. Kim, None; J. Song, None. Support: None Purpose: Tension in individual extraocular muscle (EOM) fibers can be related to overall EOM tension if the lengths and possible series-parallel arrangements of the fibers are known. Under normal conditions, EOM fibers are too small and numerous to trace them individually over any significant length. After trochlear neurectomy, however, some GL fibers in the SO become so markedly hypertrophic that they can be individually identified and studied. We exploited post-denervation hypertrophy to trace individual SO fibers throughout the length of the EOM. Methods: An adult monkey was perfused with formalin 12 mos following unilateral intracranial trochlear neurectomy (IOVS 2007; 48: 2602 - 2625). The ipsilateral orbit was embedded whole in paraffin, serially sectioned at 10 micron thickness, and stained with Masson trichrome. A group of 14 markedly hypertrophic GL fibers was identified in the SO midbelly. Each fiber was traced from high magnification micrographs posteriorly to the orbital apex, and anteriorly near trochlear entry, for a total length of ~19 mm. Results: All fibers remained within the GL. Six fibers ran the entire ~19 mm SO length without myomyous junctions, and all fibers were undivided in their posterior 13 mm. Moving anteriorly, there were 2 sets of primary myomyous division into secondary fiber pairs ~14 mm anterior to the origin, one secondary fiber dividing again 1 mm further anteriorly. Complex myomyous junctions occurred only 17 - 18 mm anterior to the origin, which is anterior to the globe-optic nerve junction, and within the sheath surrounding the SO: two pairs of fibers joined into single fibers, a secondary and tertiary branch of the same fiber rejoined, and two primary and one secondary fiber joined. Conclusions: Hypertrophic GL fibers in primate SO extend most or all of retrotrochlear SO length, and do not insert on orbital layer fibers. About half of hypertrophic GL fibers are involved in complex, interwoven myomyous junctions limited to a short extent in the anterior orbit. This suggests that the tension exerted by normal GL fibers is largely transmitted as oculorotary force to the eye. However, some non-linear force interaction is to be expected in short anterior segments of GL fibers that are involved in myomyous junctions. CR: J.L. Demer, None; V. Poukens, None; H. Ying, None; X. Shan, None; J. Tian, None; D.S. Zee, None. Support: NIH Grants EY08313, EY015025, & EY001849 Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 650-653 Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706 127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY 654 - D694 The Ultrastructural Changes of Palisade Nerve Endings in the Exotraocular Muscle After Injection of Botulinum Toxin 655 - D695 Histotopographical Study of Elastic Fibers With Special Reference to the Pulley System for Extraocular Rectus Muscles Y.-W. Suh1, M.J. Chang1, S.-H. Kim2, C.-S. Uhm 3, Y.A. Cho1. 1Department of Ophthalmology, Korea Univ Anam Hospital, Seoul, Republic of Korea; 2 Department of Ophthalmology, Korea Univ Ansan Hospital, Seoul, Republic of Korea; 3Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea. H. Osanai1, G. Murakami2, A. Ohtsuka 3, D. Suzuki1, T. Nakagawa4, H. Tatsumi1. 1 Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan; 2Iwamizawa Kojinkai Hospital, Iwamizawa, Japan; 3Department of Anatomy, Okayama University School of Medicine, Okayama, Japan; 4Idai-mae Nakagawa Eye Clinic, Sapporo, Japan. Purpose: The purpose of this study was to investigate the ultrastructural changes of palisade nerve endings after the injection of botulinum toxin A (Botox) into the extraocular muscles. Methods: Under the general anesthesia, the medial and superior recti muscles of 12 cats (24 eyes) were exposed. A dose of 5 IU of Botox (0.1 mL) was injected into the exposed extraocular muscles of one eye and 0.1 ml of normal saline was injected into the muscles of the other eye. The injection site was about 10 mm proximal to the myotendinous junction to minimize mechanical trauma of palisade nerve endings. The myotendinous junctional area was harvested at 1, 4 and 12 weeks after the injection, 4 cats at each time period. The samples were examined under electron microscope. The myotendinous junction of 4 normal cats were also examined as a normal control. Results: There was no morphological difference between normal control group and saline injection group. The proximal portion of palisade nerve endings in control group was encapsulated structure containing collagen, myelinated and unmyelinated nerve fiber. At distal palisade endings, myelinated fibers were absent, and encapsulated nerve endings contained unmyelinated fiber and collagen. At pre-terminal region, the capsular structure became incomplete. However, axon of unmyelinated fiber were completely covered with Schwann cell. In botox injection group, separation of myelin sheath, increase of neurofilament in axons of myelinated and unmyelinated nerve fiber were observed 1 week after injection, which persisted to 12 weeks. Around terminal nerve endings, incomplete Schwann cell with axonal exposure were found, and fibroblast-like change of Schwann cells were also occurred. At 12 weeks, palisade endings which was not related to the muscle fiber due to Botox induced muscle atrophy were also found. Conclusions: Botulinum toxin injected into the extraocular muscle induced ultrastructural changes of palisade nerve endings. Those alteration can influence proprioception of the extraocualr muscles. The possibility that those changes can diminish proprioception of the extraocualr muscle should be considered when botulinum toxin is used for the treatment of strabismus. CR: Y.-W. Suh, None; M.J. Chang, None; S.-H. Kim, None; C.-S. Uhm, None; Y.A. Cho, None. Support: None Purpose: To investigate the detailed configuration of the periocular elastic fibers. Methods: Semiserial paraffin sections were made using 40 whole orbital contents from 27 elderly cadavers and stained by the aldehyde-fuchsin method. Results: Periocular tissues were classified into three types according to directions of the elastic fibers, i.e., tissues containing anteroposteriorly running elastic fibers, those with mediolateral fibers and, those with meshwork of fibers. Anteroposterior elastic fiber-dominant tissue was seen in the upper eyelid and newly defined pulley plate for the medial and lateral recti (MR, LR). In the central part of the inferior rectus pulley, the mediolateral fibers were seen predominantly. In the pulley plates for the MR and LR, anteroposteriorly running fibers encased the striated muscle. Tenon’s capsule and epimysium of the recti were mediolateral fiber-dominant. However, at the entrance of the muscle terminal where Tenon’s capsule reflects and continues to the epimysium, composite elastic fibers provided a meshwork-like skeleton. The elastic mesh was also seen around the lacrimal canaliculi. Conclusions: The pulley for the recti seemed to be composed of two parts: 1) a connective tissue plate encasing the recti and 2) specialized Tenon’s capsule at an entrance or porta of the muscle. For both parts, elastic fibers were major functional components. Especially, the anteroposterior elastic fibers in the MR and LR pulley plates seemed to receive anteroposteriorly directed stress and tension from these striated muscles. The elastic interfaces seemed to prevent any concentration of stress that would interfere with periocular striated muscle functions including hypothetical active pulleys. CR: H. Osanai, None; G. Murakami, None; A. Ohtsuka, None; D. Suzuki, None; T. Nakagawa, None; H. Tatsumi, None. Support: None 656 - D696 Correlation Between Eyelid Excursion and Globe Prominence 657 - D697 Analysis of the Extra-Ocular Muscle Paths with the Delft Finite Element Model of Orbital Mechanics C. Kum, M.K. Yoon, C.C. Lin, T.J. McCulley. Ophthalmology, UCSF, San Francisco, CA. Purpose: Levator muscle function (LF) is often assessed by measuring eyelid excursion. When reductions in LF are encountered, neuromuscular disease is suspected. Despite the common use and importance of this clinical sign, little attention has been given to normal influence factors. In this study we correlate globe prominence with eyelid excursion. Methods: The study group (n=58, 22 male, 36 female, range 18 to 90 years of age) was identified from patients evaluated during the study period. Inclusion criteria were age >18 and adequate documentation of exophthalmometry measurement results and levator function, bilaterally. Exclusion criteria included any condition affecting globe or eyelid position or eyelid function (other than involutional blepharoptosis). Only right eyes were included in the calculation. Results: An analysis using Pearson’s correlation coefficient indicates a statistically significant linear relationship between LF and globe position r(56)=0.54, p<0.001. For these data, the mean (SD) for LF is 17+/-2.7mm and for globe position 15+/2.2mm. the relationship is defined by the equation y=0.432*x+8.0467 (y=LF and x=exophthalmometry measurement). Conclusions: For every 1mm change in axial globe position a mean change in LF of 0.4mm was observed. This reduction in LF with relative enophthalmos should be considered when interpreting eyelid excursion. CR: C. Kum, None; M.K. Yoon, None; C.C. Lin, None; T.J. McCulley, None. Support: None F.-W. Goudsmit1A, J.W. Moerkerken1A, S. Schutte1A, F.C.T. van der Helm1A, F. van Keulen1B, H.J. Simonsz2. ABiomechanical Engineering, BPrecision and Microsystems Engineering., 1Technical University Delft, Delft, The Netherlands; 2Department of Ophthalmology, Erasmus Medical Centre, Rotterdam, The Netherlands. Purpose: This investigation studied the importance of sliding surfaces, pressure distribution and the muscle path with the Delft Finite Element Model of Orbital Mechanics (DFEM). The path of the EOMs is determined by the tension in the muscle, the stiffness of the muscle itself and by external forces on the muscle. We investigated, with the DFEM, whether the curved path could be explained solely by interaction with the fat surrounding the rectus muscles, rather than through focal mechanical effects. Methods: The DFEM was extended to incorporate the oblique muscles and optical nerve. Geometries were obtained from MRI and meshed using 4-noded tetrahedral elements. A fine mesh was used in areas subjected to large deformations (behind the insertions of the EOM) and in the narrow area in the apex subjected to large reaction forces. The use of a fine tetrahedral mesh facilitated calculation and prevented distortion of elements. A contact algorithm (with zero friction) was employed to model sliding between the interacting tissues. Sliding was permitted between the fat and EOM, between the fat and optic nerve, between the fat and the eye. With the model both pressure distribution and muscle paths were studied. Results: Sliding permitted more eye rotation than in the previous versions of the model. The model predicted the pressure distribution in the fat behind the eye (Fig): due to the use of isotropic homogenous orbital fat, the pressure distribution was more gradual in the area between the tendon and eye than in reality. During muscle contraction high pressure gradients were found in the fat between EOM and eye. This resulted in a force orthogonal to the muscle line of action causing sharp bending (“lateral inflections”) of the muscle anteriorly. Conclusion: The model provides insight in the pressure distribution and pressure gradient in the fat tissue, underlying the curved paths of EOMs. The too gradual pressure distribution indicates the need for inhomogeneous and/or anisotropic material for the modelling of the fat. CR: F.-W. Goudsmit, None; J.W. Moerkerken, None; S. Schutte, None; F.C.T. van der Helm, None; F. van Keulen, None; H.J. Simonsz, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 654-657 Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706 127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY 658 - D698 Validation of the Delft Finite Element Model of Orbital Mechanics 659 - D699 Analysis of Ex- and Endophthalmos with the Delft Finite Element Model for Orbital Mechanics K. de Vries1A, A.M. van Ditten1A, A.G. Dunning1A, S. Ladde1A, S. Schutte1A, C.P. Botha1B, P. Wielopolski2A, H.J. Simonsz2B. ABioMechanical Engineering, BComputer Graphics, Dept. Mediamatics, Fac. EEMCS, 1Delft University of Technology, Delft, The Netherlands; ARadiology, BOphthalmology, 2Erasmus Medical Center, Rotterdam, The Netherlands. Purpose: In the Delft Finite Element Model of Orbital Mechanics, material properties are assigned to the elements based on in-vivo and post mortem measurements. We performed a validation study using high resolution MRI data and the previously measured values for viscoelasticity for a comparison with previous in-vivo measurements of passive rotational stiffness of the eye. Methods: High quality MRI data of the deformation of the orbital fat were obtained (see accompanying abstract by Dunning et al.). The orbital fat was segmented (Fig.). To estimate the displacement of the orbital fat, optical flow analysis (OFA) with the Demons and B-splines algorithms was employed. A stiffness matrix was build from finite element 8-node bricks. Material properties of the stiffness matrix were assigned according to post mortem viscoelasticity measurements on calf orbital fat (G’=250-500 Pa and G’’=80-170 Pa; Schoemaker et al. 2006). Local deformations of the orbital fat were first multiplied with the stiffness matrix of the fat to calculate the nodal forces. By multiplying these nodal forces with the deformations again, the energy of the eye movement was calculated. Dividing this energy by the angle of rotation resulted in the rotational stiffness. To validate the OFA, MRI control measurements were done by deformation of a piece of beef. Results: Stiffness in horizontal eye rotation was 30 - 480 mNmm/deg, comparable to the stiffness found in in-vivo measurements (120 mNmm/deg). In the OFA validation, translations were within 6% of the applied value, rotation within 3% and strain within 4%. Conclusions: Rotational stiffness of the eye could be derived from imaging data. This is a step towards the use of preoperative MRI and OFA to adapt the finite element model to an individual patient. CR: K. de Vries, None; A.M. van Ditten, None; A.G. Dunning, None; S. Ladde, None; S. Schutte, None; C.P. Botha, None; P. Wielopolski, None; H.J. Simonsz, None. Support: None 660 - D700 Friction in the Orbit S. Schutte1A, F. van Keulen1B, C.P. Botha1C, F.C.T. van der Helm1A, H.J. Simonsz2. A BioMechanical Engineering, BStructural Optimization and Computational Mechanics, CMediamatics, 1Delft University of Technology, Delft, The Netherlands; 2 Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands. Purpose: The human eye is suspended inside the orbit. The interaction between pressure and tensile forces in the soft tissues keeps the eye in place, while a large range of rotational motion is enabled. The eye, the extraocular muscles (EOMs), orbital fat and the optic nerve mechanically interact and exert forces on each other at every location where they touch. The large range of motion of the eye is facilitated by sliding at interfaces between tissues. It is currently unknown what the magnitude of friction is that occurs at these interface layers and how that relates to the energy lost in viscous deformations of the fat and other tissues. Methods: The main sliding areas in the orbit are (1) between the sclera and the orbital fat, (2) between the EOMs and the orbital fat and (3) between the EOMs and the orbital wall. The total amount of lost energy in eye rotations was measured post mortem in pigs by passively rotating the eye around the visual axis with a pendulum. This energy was lost in tissue viscosity and friction at the interface layers. The Delft Finite Element Model of Orbital Biomechanics, combined with the material properties of the orbital fat (G’=250-500 Pa and G’’=80-170 Pa;Schoemaker et al. 2006) and deformations of the tissues found by MRI imaging and optical flow analysis, were used to distinguish between energy lost in friction and energy lost in viscosity. Results: The amount of energy that is lost in eye movements due to friction is small(<10%) compared to the energy lost in viscosity of the tissues. Sliding in the human body is usually facilitated by a synovial-fluid like substance (mainly consisting of glycosaminoglycans and glycoproteins) which is known to cause low friction in joints. Conclusions: Sliding plays an important role in the orbit and friction at the interface layers is low. Finite-element modeling enabled estimation of the amount of energy lost in friction. CR: S. Schutte, None; F. van Keulen, None; C.P. Botha, None; F.C.T. van der Helm, None; H.J. Simonsz, None. Support: None J.W. Moerkerken1A, F. Goudsmit1A, S. Schutte1A, S.J. Picken1B, F.C.T. van der Helm1A, F. van Keulen1C, H.J. Simonsz2. ABiomechanical Engineering, BPolymer Materials and Engineering, CStructural Optimization & Computational Mechanics, 1TU-Delft, Delft, The Netherlands; 2Ophthalmology, Erasmus Medical Centre, Rotterdam, The Netherlands. Purpose: The Delft Finite Element Model for Orbital Mechanics would be well suited to simulate ex- and endophthalmos like Graves’ disease. In this study the model will be tested in order to see if the mechanics of these diseases can be simulated. Methods: Orbital pressure in- and decrease were simulated with expansion and deflation of part of the tetrahedra constituting the model. To model the orbital fat we used Herrmann elements. This type of element is used for the modeling of incompressible materials and provides the hydrostatic pressure as an additional result. The hydrostatic pressure was considered the resultant of arterial and venous blood pressure, tissue osmotic pressure and other pressures. For the simulation of ex- and endophthalmos the orbital volume was increased and decreased; first in the muscle, then in the fat and finally in the fat and the muscle. Diseases were simulated with the model: Graves’ disease was modeled by increasing the osmotic pressure and the volume of the muscles and the orbital fat. Orbital tumor was simulated by adding orbital fat volume. Cachexia was simulated by reduction of the retrobulbar fat volume. Finally caroticocavernous fistula was modeled by increasing venous blood pressure. Results: Volume and pressure in- and decrease were applied stepwise until the numerical solution could not be reached by calculation. The model allowed for ±50% expansion and deflation. Tissue swelling and deflation caused by changes in volume resulted in ex- and endophthalmos. Adding 50% volume to the orbital fat resulted in exophthalmos of 6 mm. Pressure increase on the optic nerve was considerable, pressures up to 15 mmHg were calculated by the model. Reduction of the retrobulbar fat volume of 50% resulted in endophthalmos of 4 mm. Conclusions: Ex- and endophthalmos simulations are possible in the Delft Finite Element Model for Orbital Mechanics and provide insight in the mechanics of various orbital disorders. The model is now extended to simulate the effect of various surgical approaches. CR: J.W. Moerkerken, None; F. Goudsmit, None; S. Schutte, None; S.J. Picken, None; F.C.T. van der Helm, None; F. van Keulen, None; H.J. Simonsz, None. Support: None 661 - D701 High-Resolution MRI of Horizontal Gaze Position for Improved Optical Flow Analysis A.G. Dunning1A, A.M. van Ditten1A, K. de Vries1A, S. Ladde1A, S. Schutte1A, C.P. Botha1B, P. Wielopolski2A, H.J. Simonsz2B. ABioMechanical Engineering, BComputer Graphics, Dept. Mediamatics, Fac. EEMCS, 1Delft University of Technology, Delft, The Netherlands; ARadiology, BOphthomology, 2Erasmus Medical Center, Rotterdam, The Netherlands. Purpose: Long term goal of the Delft Finite Element Model of Orbital Mechanics is to adapt the model for each individual patient using optical flow analysis (OFA) of MRI scans taken preoperatively. OFA can estimate displacements and deformations of the orbital fat by comparing two MRI datasets in different positions of gaze. However, this MRI data is marred by involuntary head movements and involuntary eye movements. We obtained high resolution data by limiting head and eye movements. Methods: A bite board of PVC with dental thermoplast was attached to a stiff MDF frame that was mounted rigidly to the MRI gantry. To track head movements, MRI markers were used to detect inadvertent head movement. A LED was rotated at equidistance in front of the dominant eye in 15 directions of gaze, from 35 degrees left gaze to 35 degrees right gaze with steps of 5 degrees. The other eye was covered. Pick-up coils were attached to the frame. Results: Two 23-year-old males were placed supine in the MRI scanner with a dentalimpression bite board. For 2 minutes 3D T1 weighted scans were made with a Sigma Excite 3.0T MRI scanner. The successive datasets were analyzed to determine any head movement. With registration of the markers displacements between successive datasets were found to be less than 0.1 mm in transversal, 0.5 mm in temporal and 0.3 mm in vertical direction. The subjects were able to focus on the LED and were able to keep their eye fixated in the applied direction of gaze: resolution of the scans in extreme left and right gaze was equal to that of the scan made in primary gaze. Conclusions: Using this approach high resolution MRI data sets were obtained and the data sets had sufficient resolution to make high resolution OFA of the deformation of orbital fat possible (see accompanying abstract by de Vries et al.). CR: A.G. Dunning, None; A.M. van Ditten, None; K. de Vries, None; S. Ladde, None; S. Schutte, None; C.P. Botha, None; P. Wielopolski, None; H.J. Simonsz, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 658-661 Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706 127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY 662 - D702 Assessment of Blepharospasm and Botulinum Toxin Effects Using Videonystagmography 663 - D703 Analysis of Microbial Growth in Reconstituted Botulinum Toxin - A Vials T.H. Osaki, M.H. Osaki, T.H. Osaki, A.E. Sant’Anna, A. Hofling-Lima, M.C. Zorat, R. Belfort, Jr.. Vision Institute, UNIFESP-Brazil, Sao Paulo, Brazil. E. Merce1A, G. Casse1A, J.-P. Adenis1A, J.-P. Sauvage1B, P.-Y. Robert1A. AOphtalmology, B ENT, 1CHU Dupuytren, LIMOGES, France. Purpose: The aim of this study was to study blinking parameters using a videonystagmography device, in order to determine objectively disability, and to assess the efficiency of botulinum toxin injection in patients with essential blepharospasm. Methods: Blinking was studied using the features of pupillary occlusion (PO) as recorded on a videonystagmography device. In 23 patients presenting with essential blepharospasm, we studied the frequency, the percentage and the mean duration of PO, and the longest PO in a 5min test time. Patients were tested prior to botulinum toxin injection, and respectively 1 month and 3 months after injection. PO of less than 0.3 s and more than 0.3 s were studied apart. Results: At 1 month after injection, botulinum toxin significantly influenced PO higher than 0.3 s, both in frequency (9.6/min ± 8.2 on Day0 and 4.7/min ± 7.2 on Month1 (p=0.004)), and in mean duration (0.95 s ± 0,84 on Day0 and 0.58 s ± 0,34 on Month1 (p=0.03)). On the other hand we found no significant effect on PO of less than 0.3 s, both in frequency (32.4/min ± 28.4 on Day0 and 31.3/min ± 29.0 on Month1 (p=0.7)) and in mean duration (0.16 s ± 0.04 at Day0 and 0.15 s ± 0.03 at Month1 (p=0.4)). Botulinum toxin significantly influenced also the mean duration of the longest PO (6,44 s ± 9.4 on Day0 and 1.55 s ± 1.9 on Month1 (p=0.004)) as well as the percentage of PO (29,95% ± 24.6 on Day0 and 13.44% ± 11.1 on Month1 (p=0.003)). Conclusions: PO can be used as the indirect sign of blinking. Videonystagmography provides a real-time result, and could be used to objectively evaluate the effect of botulinum toxin treatment in essential blepharospasm patients. CR: E. Merce, None; G. Casse, None; J.-P. Adenis, None; J.-P. Sauvage, None; P.-Y. Robert, None. Support: None Purpose: The purpose of this study was to analyze microbial growth in reconstituted Botulinum toxin - A solutions from vials stored in refrigerator for one month after use. Methods: Seventy eight consecutive 100-U vials of Botulinum toxin-A (Botox®) were reconstituted with 3.0 mL each of normal saline without preservative and were used in aseptic conditions in blepharospasm and hemifacial spasm patients. The Botulinum toxin-A solution was used to treat one or two patients in the same day. The same needle was used for aspiration (just the syringes were replaced and each patient had his own needle for application). After the applications, each vial was stored in a multiuse medication refrigerator. Four weeks later, the vials were sent to microbiological analysis. The contents of the vials were plated by microbiologists using standard techniques on blood agar, chocolate agar, Sauboraud agar and thioglycolate broth. Results: Sterility analysis with blood agar, chocolate agar, Sauboraud agar and thioglycolate broth detected no bacterial growth from the 78 vials of reconstituted Botulinum toxin-A solutions. There was not fungus growth either. Conclusions: Even though manufacturers advocate that Botulinum toxin-A shoud be used within 4 hours after reconstitution, refrigerator storage of medication vials containing reconstituted botulinum toxin (applied following aseptic precautions), did not result in microbial contamination of the contents. Therefore, the results of this study suggest that reconstituted Botulinum toxin-A can be safely stored in refrigerator for at least 1 month. CR: T.H. Osaki, None; M.H. Osaki, None; T.H. Osaki, None; A.E. Sant’Anna, None; A. Hofling-Lima, None; M.C. Zorat, None; R. Belfort, Jr., None. Support: None 664 - D704 Temporary Management of Involutional Entropion With Application of Octyl-2Cyanoacrylate Liquid Bandage (Band-Aid Liquid) 665 - D705 A Simple, Brow Based Method of Identifying Exophthalmos Correlates with Established Cases and Detects Unsuspected Cases M.H. Osaki1, T. Osaki1, T.H. Osaki1,2. 1Ophthalmology, UNIFESP, Sao Paulo, Brazil; 2 Ophthalmology, Santa Casa of Sao Paulo, Sao Paulo, Brazil. D.S. Bardenstein. Ophthalmology & Pathology, Case Western Reserve University, Cleveland, OH. Purpose: Involutional entropion affects basically the lower eyelid and is more common in older patients. It is associated with several causative factors, including horizontal lid laxity with attenuation or disinsertion of the lower lid retractors. A prospective study was designed to evaluate the use of octyl-2-cyanoacrylate liquid bandage as a temporary treatment in patients awaiting surgical repair for involutional entropion. Methods: We evaluated 10 patients (11 lower eyelids) who were awaiting surgical intervention to correct involutional entropium. The lower eyelid was repositioned by application of the octyl-2-cyanoacrylate liquid bandage (Band-Aid liquid, Ethicon, Johnson and Johnson’s, New Jersey, NY, USA) in the lower eyelid, near the lower orbital rim. Patients were followed at days 1 and 7. Assessment of eyelid correction and duration of correction were recorded. Results: All patients presented successful correction at day 1, with significant improvements in symptoms and signs. The mean duration of action of the octyl-2cyanoacrylate liquid bandage was 3.1±0.9 days. In two patients, adhesion broke at day 2; in five, at day 3; in two, at day 4 and in one, at day 5. No ocular or dermatological reactions were noted and patients were satisfied with the temporary results. Conclusions: Octyl-2-cyanoacrylate liquid bandage is a simple and effective method that provides a potentially simple solution to treat patients with involutional entropion temporarily, while they are awaiting surgical repair, as well as in patients without systemic clinical conditions or unwilling to undergo a surgical procedure. It is a safe, not allergenic and not expensive product that can be used daily (or when the adhesions break) in these cases. CR: M.H. Osaki, None; T. Osaki, None; T.H. Osaki, None. Support: None Purpose: Expert estimates suggest that 50-85% of patients with Thyroid Eye Disease (TED) are referred for evaluation later than desired. This is felt to reflect poor detection of clinical signs of this condition, such as exophthalmos (EXOPH) which can be masked by concurrent periocular alterations. In addition, most patients at risk for TED are managed by primary care and internal medicine physicians without special tools such as exophthalmometers. We sought to develop a simple method to screen for EXOPH, Lateral Brow Exophthalmometry (LBE) which could be used by most health care providers to detect EXOPH. Methods: Patients: 35 Orbit Service patients in whom we suspected EXOPH were included. Demographic data including: Age, ethnicity and gender were collected. Historic data: previous suspicion of EXOPH, previous TED, orbit fracture, chronic steroid use andother causes of EXOPH were obtained Clinical data: Hertel exophthalmometry, lid position and orbit soft tissue assessment was obtained. Objective EXOPH was defined in 1 of 3 ways: exophthalmometry readings above gender and ethnic norms, showing increase and alteration of eye position documented from prior photographs. LBE: a rounded linear rod, was held vertically, resting on the superior orbital rim in the plane of the corneal apex. LBE was considered positive (+) if the extended line of the posterior rod surface would intersect the cornea and negative if it was anterior to the corneal apex. Photodocumentation for the study was then obtained using standard camera orientation and position. Data analysis: Photographs were printed then coded and examined in a masked fashion for LBE. LBE was correlated with specialist suspicion of EXOPH, objective EXOPH and referring provider suspicion of EXOPH. Results: Patient age ranged from 25-82 years. Ethnicity included Caucasian, African American, Hispanic and Asian patients. The most common diagnosis was TED, though in over 30% of cases, EXOPH was unsuspected. Over 90% of patients with + LBE had objective EXOPH. Over 90% of patients with EXOPH suspected by the specialist showed + LBE. The exceptions included patients with TED and very deep set orbits. Similarly, over 90% of patients whose EXOPH was not suspected by referring providers had + LBE. Conclusions: LBE is an extremely simple and safe method for detecting EXOPH requiring little equipment and training. It is effective both in settings where exophthalmos is very likely as well as when it is unsuspected. This technique should greatly enhance the detection of exophthalmos and appropriate referral of patients. CR: D.S. Bardenstein, None. Support: NIH EY 11373, Ohio Lions, Research to Prevent Blindness Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 662-665 Sunday, May 3, 11:15 AM - 1:00 PM Hall B/C Poster Session Program Number/Board # Range: 646 - 666 / D686 - D706 127. Extraocular Muscles, Orbit, and Oculoplastic Organizing Section: EY 666 - D706 Assessment of the Effect of Ethnicity on the Cosmetic Outcome of Lateral Direct Brow Lifting T.J. McCulley, I. Phan, M.K. Yoon, T.N. Hwang. Ophthalmology, University of California, San Francisco, San Francisco, CA. Purpose: With the emergence of modern brow lifting techniques, the direct brow lift is rarely and probably under utilized. This avoidance is due primarily to fear of unacceptable scarring, particularly in more darkly pigmented individuals. The dermis of the lateral brow is thinner than medially and therefore less prone to scarring. In select patients with predominantly lateral brow ptosis, a modified lateral direct brow lift may serve as a reasonable alternative to larger caliber techniques. In this report we describe outcomes of ten patients of varying ethnic backgrounds who underwent lateral direct brow lifts. Methods: In this retrospective case series, we reviewed 20 brows of 10 consecutive patients (4 male, 6 female; ages 61 to 77) who underwent a direct lateral brow lift. Main outcome measure was ethnicity, need for surgical revision and the development of unacceptable scarring. Surgical technique was as follows: skin incision was made with a 15-blade scapel and unipolar cautery was used to remove the desired amount of skin and partial-thickness subcutaneous fat over the lateral half of the ptotic brow. Inferior dissection within the subcutaneous fat layer allowed mobilization of the brow superiorly. Closure was performed in three layers: subcutaneous fat using interrupted 5.0 Vicryl sutures, dermis with interrupted 5.0 Vicryl sutures and skin with a running 6.0 fast-absorbing plain gut suture. Results: Patients were of various ethnic backgrounds: Caucasians (n=6), Latinos (n=2), Filipino (n=1), and Indian (n=1). Follow-up ranged from three to seven months. No patient required surgical revision. No patient reported or was felt by the treating physician to have unacceptable scarring. There was no difference in scar visibility in Caucasian vs non-Caucasian patients (based on patient satisfaction and surgeon review of post-operative photos). All patients had good functional and cosmetic results. Conclusions: A lateral direct brow lift is a simple, minimally-invasive surgical approach that can effectively address lateral brow ptosis and associated lateral hooding. This small pilot series of patients of varied ethnic backgrounds, suggests that direct lateral brow lifting may be acceptable even in patients with various degrees of skin pigmentation. CR: T.J. McCulley, None; I. Phan, None; M.K. Yoon, None; T.N. Hwang, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 666 Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 925 - 938 / D707 - D720 148. Nerve Fiber Layer in Optic Neuropathy Organizing Section: EY 925 - D707 Prospective Follow-up of Optic Disc Topography and Circumpapillary Retinal Nerve Fiber Layer Thickness Following Initial Optic Neuritis 926 - D708 One Month Findings Predict Retinal Nerve Fiber Layer (RNFL) Loss at 6 Months After Acute Optic Neuritis K. Hayashi1, A. Tomidokoro1, M. Yanagisawa1, M. Araie1, M. Wakakura2. 1 Ophthalmology, University of Tokyo, Tokyo, Japan; 2Ophthalmology, Inouye Eye Hospital, Tokyo, Japan. S.C. Anderson1, M.J. Kupersmith2, G. Mandel2, R. Kardon1. 1Ophthalmology & Visual Sciences, VA Medical Center & Univ of Iowa, Iowa City, IA; 2Ophthalmology, Roosevelt Hospital & New York Eye and Ear Infirmary, New York, NY. Purpose: To prospectively evaluate the changes in optic nerve head topography and retinal nerve fiber layer (RNFL) thickness in patients following initial optic neuritis using the Heidelberg retina tomograph (HRT) II and scanning laser polarimetry (GDx VCC) . Methods: Eighteen eyes of 8 unilateral and 5 bilateral patients with an initial episode of acute optic neuritis were prospectively followed at the 0, 1, 3 and 6 months after the onset by HRT II, GDx VCC and visual field testing with the Humphrey Field Analyzer (HFA) 30-2 fast pack. Results: During the first 3 months after the onset, significant increase in cup area, cup/disc area ratio and linear cup/disc ratio and significant decrease of rim area in HRT parameters and significant decrease in TSNIT average, superior average and inferior average in GDx parameters were found (repeated measure ANOVA, Scheffe test, P<0.05). These parameters became stable after the month-3. Other HRT and GDx parameters showed no significant changes during the follow-up. At the month-6, superior average in GDx was significantly correlated with visual field damage (i.e. mean deviation of the HFA, R 2=0.506, P=0.0007). In 8 unilateral cases, cup/disc area ratio and cup shape measure were significantly smaller in the affected eyes than in the fellow eyes until the month-1 after the onset (P<0.05, paired t-test). These differences were no longer significant after the month-3. No GDx parameters were significantly different between the affected and fellow eyes at any time point (P>0.05). Conclusions: Changes in the optic disc topography and circumpapillary RNFL thickness were found in the first 3 months following the onset of initial optic neuritis, which possibly suggest resolving of the acute optic nerve edema and/or gradual decrease in the number of nerve fibers. Significant correlation between visual field damage and a GDx parameter may indicate the presence of the axonal damages after optic neuritis. CR: K. Hayashi, None; A. Tomidokoro, None; M. Yanagisawa, None; M. Araie, None; M. Wakakura, None. Support: None Purpose: We reported that in acute optic neuritis, RNFL shows acute swelling in greater than 80% sectors at baseline and thinning in greater than 50% of sectors at 1 month (ARVO 2008). We now report the 3 & 6 month RNFL outcomes of this first prospective study on patients followed from the onset of acute optic neuritis. Methods:35 subjects had visual & RNFL assessments using OCT 3 and scanning laser polarimetry (SLP; enhanced corneal compensation) at entry, 1, 3 & 6 months. We judged acuity worse than 20/50 or mean deviation (MD) worse than -15 db as severe vision loss. RNFL thinning for OCT & SLP was significant if 2 clock-hour sectors were 10 microns less than in fellow normal eyes. Results: RNFL sectors were thinned by SLP in 53% & 76% and by OCT in 73% and 87% of eyes at 3 & 6 months, respectively. Severe vision loss & sector thinning at 1 month correlated with thinning of the OCT average RNFL at 6 months(r=.58, p=.006 & r=.54, p=0.02). The graphs show sector and mean RNFL loss (compared to fellow eyes) over time. Note swelling of RNFL, common at entry & 1 month, precludes demonstration of early loss at one month. At 6 months, OCT mean RNFL thinning correlated with visual acuity (r=.653, p=.001) and MD (r=.725, p=.0001) assessed at that time point. Conclusions: Sector analysis with fellow eye comparison shows RNFL thinning is common in optic neuritis, particularly when visual deficits persist. Eyes with severe vision loss or RNFL thinning at 1 month have worse RNFL loss that continues passed 3 months. This corroborates the importance of the 1 month time point after an acute optic neuritis. CR: S.C. Anderson, None; M.J. Kupersmith, Teva Pharmaceutical, C; G. Mandel, None; R. Kardon, None. Support: Supported by a Veterans Affairs Merit Rehab Grant and Pearle Vision Fun 927 - D709 Clinical and Ocular Imaging Characteristics of Eyes With Visual Loss Over Time in Multiple Sclerosis 928 - D710 Structural and Functional Evaluation of the Retinal Nerve Fiber Layer in Patients With Multiple Sclerosis E. Bisker1, S. Chang1, A. Conger2, G. Hiremath 3, Y. Dai1, G.-S. Ying1, M. Maguire1, E. Frohman2, P. Calabresi 3, L. Balcer1. 1University of Pennsylvania School of Medicine, Philadelphia, PA; 2University of Texas Southwestern Medical Center, Dallas, TX; 3 Johns Hopkins School of Medicine, Baltimore, MD. E. Garcia-Martin1A,2, V. Pueyo1A,2, J.R. Ara1B, C. Almarcegui1C, J. Martin1B, I. Pinilla1A,2, M. Idoipe1A,2, F.M. Honrubia1A, J. Fernandez1A. AOphthalmology, BNeurology, C Neurophysiology, 1Miguel Servet Hospital, Zaragoza, Spain; 2Instituto Aragones de Ciencias de la Salud, Zaragoza, Spain. Purpose: The purpose of this study was to determine the degree of retinal nerve fiber layer (RNFL) thinning by optical coherence tomography (OCT) that is associated with losses of low- and high-contrast acuity over time in a multiple sclerosis (MS) cohort. Visual dysfunction and axonal loss are common in MS. The emergence of OCT has allowed us to capture the unique structure-function correlations provided by the anterior visual pathway in MS. Methods: Patients with MS underwent OCT-3 imaging at baseline and at 6-month intervals during a mean follow-up period of 1.5 years (range 0.5-3.7) at three academic centers. RNFL thickness was measured for 360º around the optic disc. Visual function testing was performed using low-contrast (2.5 and 1.25% levels) and ETDRS acuity charts. Eyes with comorbid ocular conditions or acute ON within 3 months prior to testing were excluded. Results: Among 1,148 patients (2,296 eyes, age 44±11 years) who underwent baseline assessments, 365 (725 eyes) have participated in longitudinal follow-up. Worsening of low-contrast acuity was noted in 237 eyes of 123 patients (33% of MS eyes). Approximately 1/3 of eyes with visual loss had a past history of ON. Two-line (10-letter) losses of low-contrast acuity were associated, on average, with 1.6 µm decrements in RNFL thickness over time at 2.5% contrast (p=0.009, GEE models, accounting for age and within-patient, inter-eye correlations), and 3.7 µm reductions at 1.25% contrast (p=0.02). Patients with worsening vision were only slightly older (age 45 vs. 43 years), and had slightly greater disease duration (12 vs. 11 years). Conclusions: Visual loss occurs in a substantial proportion of MS eyes, and may be present even in the absence of a history of ON. Reductions in low-contrast acuity are associated with RNFL thinning over time, suggesting that axonal loss may be a significant contributor to visual dysfunction in MS. CR: E. Bisker, None; S. Chang, None; A. Conger, None; G. Hiremath, None; Y. Dai, None; G.-S. Ying, None; M. Maguire, None; E. Frohman, None; P. Calabresi, None; L. Balcer, None. Support: National MS Society PP1115 (Dr. Balcer), National MS Society Translational Research Partnership TR 3760-A-3 (Drs. Calabresi and Balcer), National Eye Institute K24 EY 014136 (Dr. Balcer) Purpose: To evaluate the changes in the retinal nerve fiber layer (RNFL) in patients with Multiple Sclerosis (MS) by means of ocular imaging technologies and functional evaluation. Methods: Forty-six patients with MS (92 eyes) were enrolled in this study. None of the patients had an optic neuritis episode in at least 6 months prior to the inclusion or during the follow-up. All patients underwent a complete ophthalmic examination that included visual acuity (logMAR), colour vision (Ishihara pseudoisochromatic plates), refractive evaluation, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (GDx) and visual evoked potentials (VEP). All the patients were re-evaluated after a period of 12 months in order to quantify any change in the retinal nerve fiber layer. Results: All the parameters showed a decrease in the RNFL thickness during the 12-month follow-up greater than the decrease due to the age in healthy patients, although these changes were not detected by the standard automated perimetry. Differences were statistically significant (P<0,05, t test) in the mean and inferior RNFL thickness and macular volume provided by OCT and in the TSNIT SD provided by GDx. The greater differences were obtained in the mean RNFL thickness (89.70 µm vs 87.03 µm). Changes in the optic nerve were detected by structural measurements but not by functional assessments. Conclusions: The rate of axonal loss observed in patients with MS was greater than that seen in healthy patients, regardless of the presence of a previous history of optic neuritis. Progressive axonal loss can be detected in the optic nerve of MS patients. Ocular imaging technologies are useful tools to evaluate structural abnormalities in the RNFL and changes in time. CR: E. Garcia-Martin, None; V. Pueyo, None; J.R. Ara, None; C. Almarcegui, None; J. Martin, None; I. Pinilla, None; M. Idoipe, None; F.M. Honrubia, None; J. Fernandez, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 925-928 Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 925 - 938 / D707 - D720 148. Nerve Fiber Layer in Optic Neuropathy Organizing Section: EY 929 - D711 Relationship Between Optical Coherence Tomography, Pattern Electroretinogram and Standard Automated Perimetry in Eyes With Temporal Hemianopia From Chiasmal Compression 930 - D712 Correlation Between Fourier-Domain Optical Coherence Tomography Measurements of the Macular and Retinal Nerve Fiber Layer and Visual Field Sensitivity Loss in Patients With Chiasmal Compression M.L. Monteiro, L.P. Cunha, L.V.F. Costa-Cunha, O.O. Maia, Jr., M.K. Oyamada. Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil. L.C. Cunha1, L.P. Cunha2, R.F.S. Malta2, M.L.R. Monteiro2. 1Ophthalmology, University of Säo Paulo, Sao Paulo, Brazil; 2Ophthalmology, Univ de Sao Paulo, Sao Paulo, Brazil. Purpose: To evaluate the relationship between pattern electroretinogram (PERG) amplitude, optical coherence tomography (OCT) macular and retinal nerve fiber layer (RNFL) thickness and visual field (VF) loss on standard automated perimetry (SAP) in eyes with temporal hemianopia from chiasmal compression. Methods: Forty-one eyes from 41 patients with permanent temporal VF defects from chiasmal compression and 41 healthy subjects underwent transient full-field and hemifield (temporal or nasal) stimulation PERG, SAP and time domain-OCT macular and RNFL thickness measurements (Figure 1). Comparisons were made using Student’s t test. Deviation from normal VF sensitivity for the central 18° of VF was expressed in 1/Lambert units. Correlations between measurements were verified by linear regression analysis. Results: PERG and OCT measurements were significantly lower in eyes with temporal hemianopia than in normals. A significant correlation was found between VF sensitivity loss and full-field or nasal, but not temporal, hemifield PERG amplitude. Likewise a significant correlation was found between VF sensitivity loss and most OCT parameters. No significant correlation was observed between OCT and PERG parameters, except for nasal hemifield amplitude. A significant correlation was observed between several macular and RNFL thickness parameters. Conclusions: In patients with chiasmal compression, PERG amplitude and OCT thickness measurements were significant related to VF loss, but not to each other. OCT and PERG quantify neuronal loss differently, but both technologies are useful in understanding structure-function relationship in patients with chiasmal compression. Purpose: To test the correlation between fourier-domain (FD) optical coherence tomography (OCT) measurements of the macular and retinal nerve fiber layer (RNFL) and visual field sensitivity (VFS) loss on standard automated perimetry (SAP) in eyes with permanent temporal hemianopia from chiasmal compression. Methods: 35 patients with permanent temporal visual field (VF) defects and 35 age- and sex-matched healthy subjects. One eye of each subject was studied.Subjects underwent SAP (Humphrey) and macular and RNFL thickness measurements with the commercially available 3D OCT-1000 ® (Topcon). Macular thickness measurements were recorded and averaged for the central area and for each quadrant and half of that area, while RNFL thickness was measured and averaged for each sector around the optic disc. VFS loss was estimated from the temporal mean defect (the average of the 22 values of the temporal total deviation plot on the SAP 24-2 test, excluding the 2 points immediately above and below the blind spot), from the deviations from normal in six sectors and from the central 16 test points in the VF. Results: Global and sectoral macular and RNFL thickness parameters differed significantly between eyes with BA and healthy controls. Correlations were stronger between VFS loss and quadrantic or hemianopic nasal macular thickness than between VFS loss and sectoral RNFL thickness. The strongest correlation was observed between macular thickness in the inferonasal quadrant and VFS loss in the superior temporal central quadrant (ρ=0.78; R 2=61%; p<0.001). Conclusions: RNFL and macular thickness measured with FD-OCT were both topographically correlated with VFS loss in patients with temporal hemianopia from chiasmal compression. The correlation was stronger with quadrantic macular measurements than with RNFL thickness measurements. Macular thickness measurements could potentially be used to quantify neuronal loss in patients with chiasmal compression and could prove clinically useful in the detection of damage and follow-up of these patients. CR: M.L. Monteiro, None; L.P. Cunha, None; L.V.F. Costa-Cunha, None; O.O. Maia, Jr., None; M.K. Oyamada, None. Support: Fundação de Amparo a Pesquisa do Estado de São Paulo FAPESP (Nos 06/61549-6; 07/54142-0), São Paulo, Brazil and CNPq (No 309709/2007-5), Brasília, Brazil CT: www.clinicaltrials.gov, 00553761 CR: L.C. Cunha, None; L.P. Cunha, None; R.F.S. Malta, None; M.L.R. Monteiro, None. Support: None CT: www.clinicaltrials.gov, NCT00607100 931 - D713 Automated Perimetry and Laser Polarimetry in the Assessment of Nerve Fibers Involvement in Pituitary Adenoma 932 - D714 Differentiating Extra-Cellular Edema From Axonal Thickening in Papilledema Using OCT and SLP M. Bordin, G. Milano, C. Maceri, M. Colombo, M. Raimondi, S. Lanteri, L. Bossolesi, A. Briola, G.C. Rossi. University Eye Clinic of Pavia, IRCCS Policlinico S.Matteo Fundation, Pavia, Italy. J.P. Shulman1, G. Mandel2, M.J. Kupersmith1,2. 1The New York Eye and Ear Infirmary, New York, NY; 2INN, Roosevelt Hospital, New York, NY. Purpose: To point out the nerve fibers involvement in patients suffering from pituitary adenomas submitted to transphenoidal surgery. Methods: 26 patients (50+/-17,9 ys) were selected and submitted to a complete ophthalmic examination before (baseline visit) and after surgery. The post-intervention examinations were scheduled at 1, 3, and 6 months. The adenomas were classified according to Hardy classification. A kinetic test (HFA-II, stimulus I/4) was performed as a screening and in case of abnormal outcomes a static test 24-2 or 30-2 was carried out to better determine the visual field (VF) defect. The retinal nerve fiber layer (RNFL) was evaluated by GDx-VCC. Results: 3 adenomas were classified as micro and 23 as macro: the dimensions and the extrasellar extension were very eterogeneous. At baseline visit, none patients suffering from microadenoma presented VF or RNFL damages: these data were confirmed at 1, 3, and 6 months examinations. Among the macroadenomas, at baseline, 16 subjects presented normal VF while 22 had normal GDx; 6 presented bitemporal hemianopia at VF, one of them bilateral and 2 of them had mono-lateral GDx alteration; a mono-lateral defect of VF was recorded in 3 patients, 2 of them had abnormal GDx. Six months later, 5 patients out of 6 with bilateral VF defect performed a normal VF examination, 2 and 1 of them presented abnormal GDx, bilateral and mono-lateral respectively. Conclusion: The nerve fiber involvement can be pointed out only for macroadenomas with extrasellar extension classified as 2/C but a strict correlation between the clinical defect and anatomical tumor’s characteristics cannot be determined. Our data suggest that the nerve fibers involvement is mainly due to compression: the compression doesn’t cause immediately a nerve fiber loss as demonstrated by complete postoperative recovery of VF. The Gdx is able to point out persistent fiber losses in patients with recurrent disease and therefore prolonged fiber compression. CR: M. Bordin, None; G. Milano, None; C. Maceri, None; M. Colombo, None; M. Raimondi, None; S. Lanteri, None; L. Bossolesi, None; A. Briola, None; G.C. Rossi, None. Support: None Purpose: Ocular coherence tomography (OCT) and scanning laser polarimetry (SLP) effectively show retinal nerve fiber layer (RNFL) loss in glaucoma and optic neuritis. Since SLP principally depends on birefringent structures in the retina, it should be insensitive to extracellular edema. Previous studies have utilized either method to study swollen optic disks from a variety of etiologies. We investigated subjects with papilledema due to intracranial hypertension, as an in vivo model for edema of the RNFL. Methods: We prospectively studied 18 eyes of 9 subjects, with symptoms of intracranial hypertension, bilateral clinically apparent papilledema and no visual acuity loss or optic atrophy. Each subject had complete clinical evaluation, threshold perimetry using SITA 24-2, and RFNL evaluation with OCT3 and enhanced corneal compensation GDx. RNFL was judged thicker (by OCT) or had increased retardance (by SLP) when greater than the upper 95th percentile of the provided age matched controls. We calculated a percent (%) thickness ratio: Study Eye Thickness/Control Eye Thickness, for OCT and SLP. Results: Global RNFL averages were thicker in 10 eyes of 7 subjects by OCT and in 4 eyes in 3 subjects by SLP. Compared to our controls for OCT (114 μ as 95th percentile), 13 eyes in 8 subjects were thickened. Using the Zeiss controls for SLP (72.7 μ as 95th percentile), 4 eyes in 3 subjects had increased retardance. RNLF swelling (better demonstrated by OCT, Table) was more prevalent in superior and inferior quadrants. For the 13 eyes with OCT swelling, the mean for OCT%-SLP% was 78 (range 14-235) and provided a relative measure of edema. There was no correlation between the degree of swelling and visual field or visual acuity. Conclusions: Intracranial hypertension associated RNFL swelling occurs in part due to extracellular edema that is better demonstrated by OCT. SLP appears to better reflect changes within the axons (i.e. axonal dilation) that comprise the optic nerve. CR: J.P. Shulman, None; G. Mandel, None; M.J. Kupersmith, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 929-932 Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 925 - 938 / D707 - D720 148. Nerve Fiber Layer in Optic Neuropathy Organizing Section: EY 933 - D715 Retinal Thickness and Visual Function in Kjer Optic Atrophy A.A. Reis1,2, C. Mateus1, E.D. Silva1,2, M. Castelo-Branco1. 1Visual Neurosciences, IBILI, Faculty of Medicine, Coimbra, Portugal; 2Ophthalmology, University Hospital, Coimbra, Portugal. Purpose: To correlate multifocal electroretinographic responses with retinal thickness in patients with Kjer optic atrophy. Methods: Objective visual function was assessed by multifocal electroretinography (RetiScan - Roland Consult, Germany) in a population of 26 eyes of 13 patients with autosomal dominant optic atrophy. Retinal thickness measurements were also obtained in these patients by optical coherence tomography (Stratus OCT-3, Humphrey, USA). These data were compared with age-matched controls and were also correlated. Statistical analysis was performed using ANOVA at a significance level of p<0.05. Results: MfERG shows a significant decrease in amplitude in all rings of eccentricity (R1:p=0.042; R2:p=0.002; R3:p=0.0003; R4:p=0.0013; R5:p=0.0005). Decreased retinal thickness was also found in all 9 regions within 6 mm of the central retina (p<0.0001 for all pericentral regions and p=0.009 for the central one). A significant correlation between the grand averages of mfERG amplitude and retinal thickness was found (r=0.721; p=0.0305). Posthoc analysis by rings, yielded marginal significance only in ring 2 (r=0.636; p=0.056). Conclusions: Our results suggest that visual impairment in Kjer optic atrophy is not confined to the ganglion cells / nerve fiber layer (as widely described in the literature), but also by concomitant structural and functional damage in outer retinal compartments. CR: A.A. Reis, None; C. Mateus, None; E.D. Silva, None; M. Castelo-Branco, None. Support: None 934 - D716 Longitudinal Evaluation of Retinal Nerve Fiber Layer Thickness in Leber’s Hereditary Optic Neuropathy Carriers Shows Relevant Variability Over Time P. Barboni1, C.D. Ramos2, G. Savini1, M. Carbonelli1, F. Sadun 3, A. De Negri4, A. Berezovsky2, S.R. Salomao2, A.A. Sadun5, V. Carelli6. 1Studio d’Azeglio, Bologna, Italy; 2Ophthalmology, UNIFESP, São Paulo, Brazil; 3Ospedale San Giovanni, Tivoli, Italy; 4Azienda San Camillo-Forlanini, Rome, Italy; 5Doheny Eye Institute and Department of Ophthalmology, Los Angeles, CA; 6Dipartimento di Scienze Neurologiche, Bologna, Italy. Purpose: To analyze longitudinally the retinal nerve fiber layer (RNFL) thickness of Leber’s Hereditary Optic Neuropathy carriers (LHON-carriers) by means of optical coherence tomography (OCT). Methods: Sixty-two LHON-carriers were investigated during the Fifth, Sixth, Seventh and Eight International Field Investigation in Colatina, Brazil, between 2005 and 2008. All subjects are maternally related and belong to the same LHON Brazilian family carrying the homoplasmic 11778/ND4 mtDNA mutation on a haplogroup J background. The RNFL thickness was analyzed by StratusOCT using the 3.4 RNFL acquisition protocol. Changes of RNFL thickness for each quadrant and the 360° average were considered true (rather than the consequence of intersession variability of StratusOCT measurements) if they were higher than the previously reported tolerance limit of the instrument, defined as the intersession standard deviation multiplied by 2.77 (according to Budenz et al, Ophthalmology 2008;115:661). Only one eye for each subject was considered for analysis. Results: Twenty-three subjects had completed all annual examinations and were included in this study. Eleven of them (48%) showed RNFL thickness changes in at least one quadrant; in 4 eyes (17%) RNFL changes were observed in at least two quadrants. The incidence of RNFL changes was higher in the superior and inferior quadrants (5 eyes, 22%), than in the temporal (4 eyes, 18%) and nasal (2 eyes, 9%) quadrants. RNFL changes were not correlated to the optic disc area. Discussion: Along a follow-up of 4 years LHON-carriers showed changes of RNFL thickness in half of cases, suggesting that their optic nerves fibers undergo subclinical changes that do not necessarily lead to the acute phase of the disease. CR: P. Barboni, None; C.D. Ramos, None; G. Savini, None; M. Carbonelli, None; F. Sadun, None; A. De Negri, None; A. Berezovsky, None; S.R. Salomao, None; A.A. Sadun, None; V. Carelli, None. Support: None 935 - D717 Correlation of Automated Visual Fields, Spectral Domain and Time Domain Optical Coherence Tomography Findings in Eyes With Optic Nerve Head Drusen 936 - D718 Comparison of Optical Coherence Tomography Retinal Nerve Fiber Layer and Macular Thickness Measurements for the Detection of Progressive Axonal Loss Following Traumatic Optic Neuropathy V.A. Shah, N.R. Sabates, A.J. Bonham, R. Krishna. Ophthalmology, University Missouri Kansas City, Kansas City, MO. L.P. Cunha, L.V.F. Costa-Cunha, R.F.S. Malta, M.L.R. Monteiro. Ophthalmology, Univ de Sao Paulo, Sao Paulo, Brazil. Purpose: Correlation of peripapillary retinal nerve fiber layer thickness by spectral domain & time domain optical coherence tomography (OCT) with automated visual fields in patient with optic nerve head drusen. Methods: This is an institutional review board approved prospective study of 16 eyes with optic nerve head drusen & controls. After informed consent, complete medical history, ophthalmology examination, B scan ultrasonography,automated visual field, peripapillary retinal nerve fiber layer analysis (spectral and time domain OCT) was performed on all subjects (healthy and patients with optic nerve head drusens). Results: Spectral domain & time domain OCT measured RNFLT were significantly predictive of automated visual fields defects for superior and inferior segments (p< 0.05) in patients with optic nerve head drusen. The superior and inferior retinal nerve fiber layer thickness were significantly thinner in optic nerve head drusen eyes as compared to controls (p<0.01). Across normal patients and those with disease (n = 21), there were strong statistically significant correlations between spectral domain and time domain OCT measurements for both superior (r = 0.94, p < .001) and inferior (r = 0.91, p < .001) retinal nerve fiber layer readings. Regression analyses demonstrated that disease status does not affect the correlation for superior (p = .350) or inferior (p = .227) retinal nerve fiber layer. . Drusen grade & maximum intra ocular pressure were not predictive of automated visual fields defect. Conclusions: Spectral domain & time domain OCT reliably measures retinal nerve fiber layer thickness correlating with automated visual fields. Purpose: to compare the ability of optical coherence tomography (OCT) retinal nerve fiber layer and macular thickness measurements for detection of progressive axonal loss following acute traumatic optic neuropathy (TON) in a longitudinal study. Methods: three patients with unilateral TON were evaluated sequentially after trauma. Macular and retinal nerve fiber layer (RNFL) thickness measurements were obtained using OCT weekly for five weeks and around the twelfth week after trauma. Results: all patients showed progressive macular and RNFL thickness reduction. RNFL loss was apparent 2 weeks after trauma and became significant around 4 weeks and much more prominent 12 weeks after trauma. Macular thickness measurements showed reduction at 5 weeks that became significant only 12 weeks after trauma. When compared to the initial measurement macular thickness average reduction rate at the 12th week was 13.58% while peripapilary RNFL thickness average reduction rate was 59.31%. Conclusions: RNFL thickness measurements show greater and faster retinal neural reduction when compared macular thickness measurements in traumatic optic neuropathy. Although both measurements reduce significantly after trauma and both can be used for quantification of axonal loss, macular thickness measurements reduction is much smaller when compared to RNFL thickness measurements. CR: V.A. Shah, None; N.R. Sabates, None; A.J. Bonham, None; R. Krishna, None. Support: None CR: L.P. Cunha, None; L.V.F. Costa-Cunha, None; R.F.S. Malta, None; M.L.R. Monteiro, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 933-936 Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 925 - 938 / D707 - D720 148. Nerve Fiber Layer in Optic Neuropathy Organizing Section: EY 937 - D719 Optic Nerve and Retinal Nerve Fiber Layer Studied by Oct, Gdx and Hrt in Patients With Type I Diabetes 938 - D720 Multifocal Photopic Negative Response (mfPhNR) and Retinal Nerve Fiber Layer Thickness (RNFLT) in Normals and the Patients With Optic Nerve Lesions M. Idoipe Corta, III1,2, E. Garcia-Martin1,2, I. Pinilla1,2, L. Gil-Arribas1,2, E. Abecia1, A. Ferreras1, V. Pueyo1,2. 1Ophthalmology, Hospital Miguel Servet, Zaragoza, Spain; 2 Instituto Aragones de Ciencias de la Salud, Zaragoza, Spain. A. Kamei1, E. Nagasaka2. 1Ari Eye Clinic, Oshu-Mizusawa, Japan; 2Mayo Corp., Inazawa, Japan. Purpose: To determine the ability of Confocal Scanning Laser Ophthalmoscope (SLO), Heidelberg Retina Tomograph (HRT) and Scanning Laser Polarimeter (GDx-VCC) to detect optic nerve neuropathy and loss of the retinal nerve fiber layer (RFNL) previous the development of retinopathy in in patients with type I diabetes. Methods: Comparative cross-sectional study. Fifty eyes of 50 healthy subjects and 50 eyes of 50 patients with type I diabetes mellitus were studied. Ophthalmic examination of diabetic patients showed no retinopathy. One eye per patient was randomly selected for the study. The nerve fiber layer thickness was measured using polarimetry (GDxVCC) (NFA, Laser Diagnostic Technologies Inc, San Diego, CA, USA) and with Optical Coherence Tomography OCT (OCT2: Carl Zeiss Meditec, Dublin, California, USA). The optic disc was measured with HRT3 (HRT3: Heidelberg Engineering, Dossenheim, Germany). Results: The control group was formed by 16 women, 34 men, aged 24-40 yr (mean 28.89 ±4.68). Diabetic patients were 16 women and 34 men, aged 25.56 yr (±10.49). Mean period from the onset of diabetes was 12.8 years (SD 9.40). None of the diabetic group had changes at the fundus examination. No differences were found in GDx or OCT measuremens between control and diabetic group. We did found differences in HRT measurements including linear cup/disc ratio, cup shape measure, rim area, rim volume, height variation contour, and mean RNFL thickness. Conclusions: HRT can detect optic disc topography abnormalities in type I diabetes mellitus patients before the development of diabetic retinopathy. Neither GDx or OCT are able to find differences in the retinal nerve fiber layer thickness in diabetic patients without retinopathy. These data support the importance of the neuropathy in diabetic patients and the need of increasing our knowledge about its pathogenesis and risk factor. CR: M. Idoipe Corta, III, None; E. Garcia-Martin, None; I. Pinilla, None; L. GilArribas, None; E. Abecia, None; A. Ferreras, None; V. Pueyo, None. Support: None Purpose: To evaluate the interrelation of mfPhNR and RNFLT in the superior and inferior region in normals and patients with optic nerve lesion. Methods: Ten eyes of ten volunteers with normal vision and six eyes of three patients with optic nerve lesions including normal tension glaucoma (NTG) were tested. The mfPhNR was recorded with the VERIS Science System 5.0.4. The visual stimulus was made up of 37 hexagons in an approximately 40-degree visual field, Pseudo-randomly alternating between black (5cd/m2) and white (200cd/m2) on the CRT monitor. Burian-Allen ERG Electrodes, Adult-bipolar or Pediatric-bipolar, were used for this testing. The recording time was approximately 8 min. with dilated pupils having the best-corrected visual acuity. The band pass filter of the amplifier was set from 1 to 100 Hz. The amplification and stimulus frequency were set to 10000 and 9.41 Hz (8 frames) respectively. Each trace of the mfPhNR found in all the superior and inferior regions was analyzed. RNFLT was measured using Cirrus HD-OCT. The average RNFLT in all superior and inferior quadrants was applied for analysis. Results: There was a correlation between the amplitude of the mfPhNR in the superior region and RNFLT in the inferior quadrant (R=0.7575, P=0.0230) in normals. On the other hand, there was no correlation between the amplitude of the mfPhNR in the inferior region and RNFLT in the superior region in normals. The amplitude of mfPhNR in the eyes with optic nerve lesions decreased not only in the RNFLT decreasing quadrant but also the normal RNFLT quadrant. In unaffected eye of the patient with optic nerve lesion, the amplitude of mfPhNR was within normal range. In more affected eyes and less affected eyes with NTG, the amplitude of mfPhNR decreased in RNFLT decreasing quadrants but also normal RNFLT quadrants. Conclusions: There is a different correlation between the amplitude of the mfPhNR and RNFLT in superior and inferior quadrants in normals. The amplitude of mfPhNR decreased even in patients with normal RNFLT quadrants. CR: A. Kamei, None; E. Nagasaka, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 937-938 Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 1127 - 1137 / D1089 - D1099 157. Strabismus Surgery Organizing Section: EY Contributing Section: RE 1127 - D1089 Pseudo-Brown’s Syndrome With Superior Rectus Muscle Recession: A New Complication of Vertical Muscle Surgery 1128 - D1090 Downshoot in Infra-adduction in Strabismus With A-pattern: Post Surgical Evolution Following Selected Superior Oblique Surgical Weakening Procedures J.A. Galvin, S.M. Archer. Ophthalmology, University of Michigan, Ann Arbor, MI. E.A. Urrets Zavalia1, J.I. Torrealday1, F.A. Esposito1, H.M. Serra2, J.A. Urrets-Zavalia1. 1 Ophthalmology, University Clinic Reina Fabiola, Universidad Catolica de Cordoba, Cordoba, Argentina; 2CIBICI-CONICET, Faculty of Chemical Sciences, Universidad Nacional de Cordoba, Cordoba, Argentina. Purpose: Superior rectus surgery may cause unique complications including ptosis and eyelid retraction. We describe a new strabismus complication causing a profound limitation of elevation in adduction, simulating a Brown’s syndrome. We present a small series of patients with an unusual complication of superior rectus muscle insertion into the superior oblique tendon after recession. Methods: Retrospective chart review. Results: Three patients with the operative finding of superior rectus muscle insertion into the anterior border of the superior oblique muscle--without direct attachment to the sclera--after previous superior rectus muscle recession were identified. Findings included a large hypotropia of the affected eye with duction and version findings suggesting Brown’s syndrome. Exploration, separation from the superior oblique tendon and advancement of the superior rectus muscle with direct scleral attachment was corrective in two cases. The third case required further resection of the superior rectus muscle and superior oblique tenotomy. Discussion: Recession of the superior rectus muscle can result in a mechanical strabismus, which resembles Brown’s syndrome. Patients demonstrate a limitation of elevation due to (1) lack of a direct scleral insertion and (2) tension on the superior oblique tendon on attempted upgaze. Additional factors that may promote this complication include the hang-back recession technique, perhaps with inadequate lysis of the frenulum between the superior rectus and superior oblique muscles. Conclusions: Identification of the etiology of a vertical deviation resembling a Brown’s syndrome following superior rectus recession surgery is important. Non-scleral insertion of the superior rectus muscle into the superior oblique tendon should be suspected when an unexpected large hypotropia occurs after superior rectus muscle recession. CR: J.A. Galvin, None; S.M. Archer, None. Support: Heed Ophthalmic Foundation Purpose: To evaluate the occurrence of postsurgical true/pseudo superior oblique muscle overaction (SOOA) following treatment of A-pattern strabismus and its possible causes. Methods: 30 patients with A-pattern strabismus and symmetric SOOA were consecutively treated with 3 different superior oblique muscle (SOM) weakening surgical procedures according to degree of presurgical anisotropia and SOOA. 19 patients underwent a posterior partial tenectomy (PPT), 6 a temporal tenotomy (TT) at 4mm from scleral insertion and 5 a posterior transposition recession (PTR). The same procedure was performed in both eyes of a same patient. Results: Mean postsurgical correction of A-anisotropia was 73.9% in patients treated with PPT, 83.3% with TT and 84% with PTR. Persistence of downshoot in infra-aduction (DSIA) (true/pseudo SOOA) occurred in 12 out of 19 patients (63%) treated with PPT, in 2 of 6 (33%) with TT and in 5 of 5 (100%) of those treated with PTR. Mean DSIA correction was 56.4% in patients treated with PPT, 79.9% with TT and 25% with PTR. Conclusions: A high prevalence of postsurgical DSIA in patients with A-pattern treated with selective surgical procedures performed on SOM was observed. Apparently all 3 different surgical procedures used were useful in reducing horizontal action of SOM, with less effect on its vertical action. Eliminating A-pattern, natural vertical movements promoted by SOM such as depression in infra-adduction and slight elevatio in infra-abduction would become more evident, giving the impression of SOM hyperfunction exacerbation. As the least traumatic procedure TT gave the lowest occurence of DSIA. CR: E.A. Urrets Zavalia, None; J.I. Torrealday, None; F.A. Esposito, None; H.M. Serra, None; J.A. Urrets-Zavalia, None. Support: None 1129 - D1091 Clinical, Tomographic and Genetic Study of Two Mexican Patients With Congenital Fibrosis of the Extraocular Muscles 1130 - D1092 Inferior Oblique Surgery for Restrictive Strabismus in Patients with Thyroid Orbitopathy N. Pereyra-Munoz1A, C.E. Murillo-Correa1B, S. Flores-Limas1C, J.C. Zenteno1D. A Integral Ophthalmology, BStrabismus, CRadiology, DGenetics-Research Unit, 1 Ophthalmology Institute “Fundación Conde de Valenciana”, Mexico City, Mexico. S.A. Newman. Ophthalmology, University of Virginia, Charlottesville, VA. Purpose: Congenital fibrosis of the extraocular muscles (CFEOM) is a non-progressive disorder of ocular motility characterized by restrictive ophthalmoplegia and congenital blepharoptosis. Three types of CFEOM exist. CFEOM1 and CFEOM3 are due to mutations in KIF21A, a gene located in chromosome 12q12 and encoding a member of the kinesin family of proteins involved in the transport of essential cellular components along axonal and dendritic microtubules. Mutations in KIF21A are believed to cause alterations in axonal routing and transportation which lead to ocular motility disorders. KIF21A arginine residue at position 954 is altered in more than 80% of all individuals with KIF21A mutations reported to date. The analysis of CFEOM patients from distinct ethnic groups would help to establish the relative frequency of specific KIF21A mutations. The purpose of this study was to identify mutations in the KIF21A gene in two Mexican patients with CFEOM. Methods: Two unrelated patients with CFEOM consulting at the Ophthalmology Institute “Fundación Conde de Valenciana” in Mexico-City were included. A complete ophthalmologic examination, orbital CT and analysis of the KIF21A gene by means of PCR and automated sequencing, were performed in both subjects. Results: Both cases were sporadic. Patient 1 was a 19 year old girl with a best corrected visual acuity (BCVA) of 20/25 in the right eye (OD) and 20/40 in the left eye (OS). She had undergone two eye surgeries before presenting. She showed limitations in all gaze directions, particularly in supraversion, and bilateral ptosis. CT evidenced bilateral thinning of the superior muscular complexes. Patient 2 was a 9 year old girl with a BCVA of 20/70 OD and 20/40 OS. She had bilateral limitations in all gaze directions, paradoxical convergence, occlusion nystagmus, esotropia and bilateral ptosis. CT showed fibrosis of the extraocular muscles. In both patients, genetic analysis disclosed an identical c.2860C>T point mutation, predicting a change from arginine to tryptophan at residue 954 (R954W). Conclusions: We report two cases of Mexican patients with CFEOM, which had an R954W mutation in KIF21A. Our results support previous findings indicating that recurrent, de novo mutations at KIF21A R954 are the most common CFEOM cause in different populations. CR: N. Pereyra-Munoz, None; C.E. Murillo-Correa, None; S. Flores-Limas, None; J.C. Zenteno, None. Support: Patronage of the “Fundación Conde de Valenciana” Purpose: Thyroid orbitopathy (TO) is the most common cause of restrictive strabismus. Patients often present with vertical and/or horizontal double vision due to restriction involving most commonly the inferior and medial rectus muscles. Traditional muscle surgery involves release of the tight muscles. Previous literature has described frequent need for secondary operations and over correction incidence of up to 50%. Recognizing that the tight muscles are also limited in their excursion; it was proposed that operating on the better moving eye particularly the inferior oblique (IO) might produce an improvement in binocularity and decrease the incidence of over correction. Methods: A total of 42 patients with restrictive strabismus due to TO treated at the University of Virginia over 12 years with inferior oblique surgery were retrospectively reviewed. Results: Thirty nine patients were treated initially with inferior oblique surgery. Of these 28 patients required secondary procedures. Four patients were over corrected and a total of 24 patients were under corrected. A total of 3 patients were treated with IO surgery as a secondary procedure. Five patients were treated with additional muscle procedures at the time of IO surgery (3 medial rectus (MR), 1 superior rectus (SR) and 1 lateral rectus (LR)). At the time of last follow up ranging from 6 months to 8 years 23 had no diplopia, 2 had minimal diplopia and 2 had persistent diplopia. All but two were completely functional. Conclusions: Inferior oblique surgery by balancing the overall excursion of extraocular muscles in thyroid patients may produce binocularity in primary position and down reading gaze. There appears to be an increase in the area of binocular single visual and a decrease in the incidence of over correction with the use of inferior oblique surgery. The use of the Hess screen and binocular single vision fields is helpful in assessment and planning of surgery in these patients. CR: S.A. Newman, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1127-1130 Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 1127 - 1137 / D1089 - D1099 157. Strabismus Surgery Organizing Section: EY Contributing Section: RE 1131 - D1093 Modern Management of Hypertropia in Thyroid Eye Disease With Adjustable Sutures 1132 - D1094 Surgical Results of Lateral Recti-Recession and Monocular Recess-Resect in Exotropia for Patients With a Dominant Fxating Eye N. Mirza-George1, G. Binenbaum1, N.J. Volpe2. 1Ophthalmology, Children’s Hospital of Philadelphia, Philadelphia, PA; 2Ophthalmology, Scheie Eye Institute/University of Pennsylvania, Philadelphia, PA. B. Dufay-Dupar, B. Roussat, F.-X. Brousseaud, T. Rodallec, R. Adam, O. Laplace, J.-P. Nordmann. Ophthalmology, NIH, Paris, France. Purpose: Restrictive vertical strabismus due to thyroid eye disease (TED) is challenging to correct. We report the clinical outcomes of a management approach employing adjustable sutures. Methods: Retrospective case series . 41 subjects with TED and hypertropia underwent unilateral or bilateral adjustable-suture inferior rectus recession (IRRec) by one surgeon (NJV). Surgery variably included non-adjustable superior rectus recession (SRRec) on the hypertropic eye. Intraoperative forced-ductions determined number of vertical muscles recessed. Post-adjustment goal was orthotropia or undercorrection in primary gaze without hyperdeviation in downgaze ipsilateral to IRRec. Outcomes were vertical alignment within 5pd of orthotropia, diplopia, reoperation, and need for prisms. Results: Forty subjects had preoperative diplopia. Median preoperative primaryposition deviation was 12pd (range 4-50). 21(66%) subjects had unilateral IRRec; 14(34%) bilateral. 17(41%) subjects had SRRec. 8 patients were adjusted same-day, 33 next-day. On long-term follow-up (mean 41wks), no subjects had diplopia, although two subjects required re-operation (4.9%/95%CI 0.6-16.5) and 13(32%) required prism (9/13 were <5pd). 8 of these 15 subjects had overcorrections. 33(80%) subjects had successful vertical alignment after one surgery, of which 21 were orthotropic. In multivariate regression, day of adjustment, number of vertical muscles recessed, and previous decompression did not affect outcomes. Conclusions: Previous TED studies report a reoperation rate of 17-45%. Our findings suggest that using adjustable-sutures, operating on multiple muscles if indicated, and planning for postoperative IR weakening can reduce this rate. While 1/3 of patients required prisms, long-term deviations were small. We conclude that TED-associated hypertropia can be successfully managed with unilateral and bilateral adjustablesuture IRRec, with or without supplemental SRRec. CR: N. Mirza-George, None; G. Binenbaum, None; N.J. Volpe, None. Support: NIH Grant EY015398 1133 - D1095 Same Day Triple Therapy With Reduced Fluence Photodynamic Therapy, Intravitreal Dexamethasone and Bevacizumab in Patients With Neovascular Age-Related Macular Degeneration Purpose: To report the median term outcome of the results between bilateral recession of the lateral recti (BLR) and monocular recess-resect procedure (RR) for the correction of exotropia of patients with a dominant fixating eye. Methods: The medical records of 70 patients with exotropia who underwent surgery for exotropia from January 2002 to April 2008 and followed up for more than 6 months were reviewed retrospectively. The inclusion criteria were: basic type exotropia or and pseudo-divergence excess with or without normal stereopsis, with an invariably fixating eye. These patients underwent BLR or unilateral RR procedures on the nondominant eye; surgical outcomes were compared. An outcome was considered satisfactory if there was between 10 prism diopters of exophoria/tropia and 10 prism diopters of esophoria/tropia at 6 months after surgery. Results: In the BLR group, success was obtained in 57.1% of the patients (20 of the 35 patients). There was no case of overcorrection in the BLR group. In the RR group, 27 of the 35 patients (77.1%) had a satisfactory outcome; 3 patients (8.6%) were overcorrected. All overcorrected patients in the RR group had poor stereoacuity. The surgical success was significantly higher in the RR group than in the BLR group (P <0.01, MannWhitney U test). Conclusions: For the correction of exotropia of patients with a dominant fixating eye the unilateral RR procedure seems to be better than BLR recession surgery. When no dominant eye is shown the two procedures can be considered to be equally effective. But, the overcorrection rate was higher in the unilateral RR group. CR: B. Dufay-Dupar, None; B. Roussat, None; F.-X. Brousseaud, None; T. Rodallec, None; R. Adam, None; O. Laplace, None; J.-P. Nordmann, None. Support: None 1134 - D1096 Age-Related Immune Defects Causing Endophthalmitis After Strabismus Surgery in Young Children or in Elderly S.M. Couch, S.J. Bakri, C.A. McCannel, A.O. Edwards. Ophthalmology, Mayo Clinic, Rochester, MN. Purpose: To report the results of same day triple therapy with reduced fluence photodynamic therapy (PDT), intravitreal dexamethasone, and bevacizumab in patients with neovascular age-related macular degeneration (AMD). Methods: Retrospective case series of thirty one patients with neovascular AMD. All patients who received same day triple therapy with reduced fluence photodynamic therapy (25 J/cm2), intravitreal dexamethasone (200mcg) and intravitreal bevacizumab (1.25mg). Main outcome measures were Snellen visual acuity (VA), central macular thickness (CMT) on optical coherence tomography (OCT), need for retreatment, intraocular pressure, and endophthalmitis occurrence. Results: Average followup for the thirty one patients was 13.7 months. In all patients, mean baseline VA was 20/80 and vision at final followup was 20/60 (p=0.69). In patients who received previous treatment for exudative AMD (n=18), mean baseline VA was 20/100 and vision at final followup was 20/100 (p=0.31). In treatment-naïve patients (n=13), mean baseline VA was 20/60 and vision at final followup was 20/40 (p=0.31). In all patients, mean CMT was 293 um at baseline and 245 um at final followup (p=0.053). In previously treated patients (n=18) mean CMT was 325 um at baseline and 265 um at final followup (p=0.10). In treatment-naïve patients, mean CMT was 249 um at baseline (n=13) and 218 um at final followup (p=0.34). Previously treated patients required more anti-VEGF injections (mean = 3.6) than treatment-naïve patient (mean = 0.8), but the mean number of repeat triple therapy treatments was 0.3 in both groups. Changes in intraocular pressure and endophthalmitis were not observed during followup. Conclusions: Same-day combination therapy with reduced fluence PDT, intravitreal bevacizumab and dexamethasone preserved visual acuity and decreased macular thickness in patient with and without previous anti-VEGF therapy. Same-day triple therapy may reduce the number of anti-VEGF injections in some patients and stabilize vision in some patients not responding to anti-VEGF therapy. CR: S.M. Couch, None; S.J. Bakri, Novartis, Genentech, Alcon, C; C.A. McCannel, Genentech, C; A.O. Edwards, None. Support: None H.J. Simonsz1A, M.R. Batstra2, C.M. Mooy1B, W.B. van Leeuwen1C, K.U. Löffler3, N.G. Hartwig1D. AOphthalmology, BPathology, CMedical Microbiology and Infectious Diseases, DPediatrics, 1Erasmus Medical Center, Rotterdam, Netherlands; 2 Immunology, Reinier de Graaf Hospital, Delft, Netherlands; 3University Eye Clinic, Bonn, Germany. Purpose: We previously reported (ARVO 07) on 14 cases of endophthalmitis after strabismus surgery. These were either children under 6 who underwent a medial rectus recession and had a poor outcome, or elderly over 65 who had been operated previously on the involved eye and had a favorable outcome. We sought for age-related differences in immune response that could underlie the 2 distinct presentations. Methods: The index case was a 2-year-old girl with a previous right abducens palsy after otitis media with 41.9°C. An encapsulated, mucoid H. influenzae was cultured from the vitreous and, after enucleation 2 years later, from purulent discharge of the socket. Homology was examined with multi locus sequence typing (MLST). Her immune response and that of 3 other children and 2 elderly were assessed. Specifically, Pneumococcus IgG type 1, 3, 4, 5, 9 and 23 (against bacterial capsular polysaccharides) were measured. Enucleated eyes of the index case, of 2 other children and 1 elderly were studied histopathologically. Results: MLST showed that the 2 strains of H. influenzae from the index case were not related: 6 of 7 alleles were different. She had had no retinal detachment until vitrectomy 3 weeks later. Pathology showed no perforation: the deeper layers of the sclera were undisturbed. Underneath the suture tract the channel for the long posterior ciliary artery was located, however. Levels of all 6 types of Pneumococcus IgG were < 0.35 ug/ml (2 out of 6 may be considered normal). A 12-year-old boy, operated at 4, had 4 types < 0.35 ug/ml; his eye is phtysic. A 6-year-old girl, operated at 3, had 2 types and a 16-year-old boy, operated at 2, had 3 types < 0.35 ug/ml; both enucleated phtysic eyes had an area of transscleral scarring compatible with perforation. A 65-year-old woman had 2 types and a 71-year-old man had 1 type < 0.35 ug/ml, scleral perforation had occurred in both cases. Conclusions: The type of endophthalmitis after strabismus surgery that occurs in young children can be caused, in part, by immune defects of the type that resolves when the IgG armentarium unfolds. A contaminated suture may then cause it even without scleral perforation. Although the immune response against capsular polysaccharides decays in senescence, we could not detect this in 2 elderly cases. As all 8 cases in young children originated from medial rectus recessions and some had had upper respiratory infections, the possibility of reflux from the lacrimal sac needs further study. CR: H.J. Simonsz, None; M.R. Batstra, None; C.M. Mooy, None; W.B. van Leeuwen, None; K.U. Löffler, None; N.G. Hartwig, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1131-1134 Sunday, May 3, 2:45 PM - 4:30 PM Hall B/C Poster Session Program Number/Board # Range: 1127 - 1137 / D1089 - D1099 157. Strabismus Surgery Organizing Section: EY Contributing Section: RE 1135 - D1097 Recurrent Horizontal Strabismus with the Same or Larger Angle of Misalignment 1136 - D1098 Strabismus Surgery Under Lidocaine 2% Gel I. Zundane, S. Bruneau, R. Adam, E. Constantini, E. Tiberghien, B. Dufay-Dupar, F.-X. Brousseaud, T. Rodallec, J.-P. Nordmann. Ophthalmology, Hospital XV-XX, Paris, France. S.P. Christiansen, C.T. Bramante. Ophthalmology, University of Minnesota, Minneapolis, MN. Purpose: To investigate potential predisposing factors for postoperative horizontal strabismus that recurs with an equivalent or larger angle. Methods: The records of 1358 patients who underwent strabismus surgery by one surgeon were reviewed. Patients who met eligibility criteria and who had recurrent strabismus with a postoperative angle that matched or exceeded the original deviation were analyzed. All pre- and postoperative alignment testing was performed by the same surgeon with children wearing their full hyperopic correction if indicated. Preoperative clinical characteristics were assessed. Results: Sixteen patients (1.2%) met eligibility requirements. Of these, 4 (25%) had restrictive strabismus and 4 (25%) had paralytic strabismus. These were not analyzed further. Eight of 16 patients (50%) had non-restrictive, non-paralytic esotropia (7) or exotropia (1). Among these, 5 of 8 (62.5%) had a distance < near discrepancy of more than 10 prism diopters (PD). The mean preoperative deviation was 23 PD at distance and 35 PD at near. Three of 8 (37.5%) had hyperopia > 4.00 diopters. For all 16 patients, mean age at the time of initial surgery was 28 years (range 3.4-67.3, median 18.8). All patients underwent further surgery. Postoperative alignment improved to < 10 PD in 10 of 16 patients (62.5%) after their final surgery. Conclusions: Recurrent horizontal strabismus that matches or exceeds the original deviation is rare but may be more common in patients with restrictive and paralytic forms of strabismus or in those with significant distance-near discrepancy. These data must be interpreted with caution due to the small number of patients. CR: S.P. Christiansen, None; C.T. Bramante, None. Support: Research to Prevent Blindness, Inc Purpose: to evaluate lidocaine 2% gel efficacity in the strabismus. surgery Methods: 20 patients with horizontal muscles strabismus 4 with esotropia, 6 with exotropia were included in the study. Deviation angle was from 35 prisms to 50 prisms. ). The surgery was performed on 2 to 3 horizontal muscles per patient (mean 2.75). All were adult patients. 19 cases were 1st surgery, 1 case was 2nd surgery. All cases were operated under lidocaine 2% gel local anesthesia. The perception of discomfort or pain was evaluated by all patients between 1 (very painful) and 10 (no subjective discomfort) during the surgery and the patients satisfaction was estimated the same way on the day one. The difficulty of performing the procedure was evaluated by two operating surgeons between 1 (very difficult) and 4 (very easy to perform the surgical intervention). The patient’s compliance during surgery was evaluated between 1 (no compliance) and 10 (good compliance). The time of stay in operating room was compared between 20 cases of topical anesthesia by adult patients of this study and 20 cases of standard strabismus surgery cases under general anesthesia of adult patients performed by the same surgeons. The satisfaction after surgical manipulation was evaluated as well on day 1 on the scale between 1 (a lot of subjective discomfort) and 10 (very satisfied). Results: the mean patient satisfaction was 8.5 during the surgery, the range was 6 to 10. The group of patients under local anesthesia presented higher subjective satisfaction rate as the patients under general anesthesia (p> 0.02). The difficulty of performing the surgery was evaluated by the first surgeon 3 (the range was 2 to 4). Three patients needed to be potentialised with Midazolam during the surgery. 1 patient potentialized by Midazolam was previously a drug abuser. The compliance of the patient correlated with difficulty of performing the surgery and patient satisfaction (p>0.02) and the surgeon’s experience with this surgical technique an important factor of the success. Conclusions: carefull selection of adult patients permits to perform the strabismus surgery under local anesthesia of Lidocaine 2% gel. CR: I. Zundane, None; S. Bruneau, None; R. Adam, None; E. Constantini, None; E. Tiberghien, None; B. Dufay-Dupar, None; F.-X. Brousseaud, None; T. Rodallec, None; J.-P. Nordmann, None. Support: None CT: If Other, enter the registry site and corresponding number 1137 - D1099 Dose and Pattern of Strabismus Surgery Under Topical Anesthesia J. Tejedor1,2, C. Ogallar1. 1Ophthalmology, Hospital Ramón y Cajal, Madrid, Spain; 2 Faculty, Universidad Autónoma de Madrid, Madrid, Spain. Purpose: To compare surgical dose of strabismus surgery using topical anesthesiaadjusted dose in cooperative patients, with theoretical commonly used classic guidelines dosage. Methods: Forty cooperative patients, requiring surgery for esotropia (n=20) or exotropia (n=20), were operated using topical anesthesia. Restrictive and paralytic strabismus cases were excluded. Visual acuity, refraction, binocular function (Bagolini lenses and synoptophore), and deviation angle (prism and cover test) were determined in all patients. The amount of surgery under topical anesthesia was adjusted intraoperatively. Linear regression models for topical and theoretical dosage were adjusted and compared. We also studied theoretical dosage versus difference between topical and theoretical dosage. Results: The amount of surgery required using topical anesthesia in patients with esotropia was 5.77 mm (95%CI: 5.26-6.28), i.e., 2.6 mm less on average (95%CI: 2.39-2.80) than indicated by theoretical guidelines. In exotropic patients, the total amount of surgery required using topical anesthesia was 10.52 mm (95%CI: 9.53-11.51), 0.92 mm less on average (95% CI: 0.13-1.71) than indicated in table guidelines. Intercept and slope values were significantly different between a dose/surgery linear regression model with topical anesthesia and a theoretical model, for patients with esotropia. Motor success rates with topical anesthesia were similar in esotropia and exotropia (17/20, 85%). Conclusions: Topical anesthesia may be particularly advantageous in cooperative patients with esotropia, decreasing time and risk of additional surgery. CR: J. Tejedor, None; C. Ogallar, None. Support: FIS Grant PI 040643 Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1135-1137 Monday, May 4, 8:30 AM - 10:15 AM Palm A Paper Session Program Number Range: 1204 - 1210 202. Strabismus I Organizing Section: EY 1204 - 8:30AM Improvement in Health Related Quality of Life in Adults Following Strabismus Surgery 1205 - 8:45AM Long-Term Effectiveness of Treatments for Symptomatic Convergence Insufficiency in Children 9 to 17 Years Old J.M. Holmes, S.R. Hatt, D.A. Leske. Department of Ophthalmology, Mayo Clinic, Rochester, MN. M. Scheiman1, M. Kulp2, G. Mitchell2, S. Cotter3, M. Rouse3, R. Hertle4, Convergence Insufficiency Treatment Trial Study Group. 1Eye Institute-Coll of Optometry, Pennsylvania College of Optometry, Philadelphia, PA; 2Coll of Optometry, Ohio State University, Columbus, OH; 3Southern California College of Optometry, Fullerton, CA; 4Children’s Hospital Of Pittsburgh, Pittsburgh, PA. Purpose: To compare the responsiveness of 2 health related quality of life (HRQOL) instruments, the new strabismus-specific AS-20 and the NEI VFQ-25, in adults undergoing strabismus surgery. Methods: 37 adults with strabismus (aged 21 to 82 years, median 51) who were successfully aligned postoperatively, completed the AS-20 and VFQ-25 preoperatively and a median of 8 weeks postoperatively (range 4 to 13 weeks). 25 patients had diplopia, and 12 had no diplopia. Each questionnaire (overall and subscales) was scaled from 0 (worst HRQOL) to 100 (best HRQOL). 95% limits of agreement (LOA) for both AS-20 and VFQ-25 were defined in a previous test-retest study and real change in HRQOL was defined as change exceeding the 95% LOA. We compared proportions of patients showing real change. Results: Overall, more patients showed an improvement in AS-20 score compared to composite VFQ-25 score (21 [58%] of 37 vs 11 [30%]; P=0.01). Analyzing by whether the patient had diplopia or not, more patients without diplopia showed improvement in AS-20 than VFQ-25 (7 [58%] of 12 vs 0 of 12). On AS-20 subscales, 8 (67%) of 12 improved on the psychosocial subscale and 1 (8%) improved on the function subscale. On the 5 potentially useful VFQ-25 subscales (identified in a previous study), only 2 (17%) of 12 non-diplopic patients improved on Vision-specific (VS) role difficulties and VS social functioning subscales, and only 1 (8%) improved on VS dependancy; no patients showed improvement on the VS mental health and Peripheral vision subscales. In contrast, for diplopic patients, the AS-20 and VFQ-25 were more comparable. Similar proportions showed improvement in composite AS-20 and VFQ-25 scores (14 [56%] of 25 vs 11 [44%]; P=0.3). On AS-20 subscales, 10 (40%) of diplopic patients improved on the function subscale and 6 (24%) improved on the psychosocial subscale. On the 5 potentially useful VFQ-25 subscales, the proportion of diplopic patients showing improvement ranged from 54% to 12%: VS role difficulties: 13 (54%) of 25, VS mental health: 12 (48%), VS dependancy: 8 (32%); VS social functioning: 5 (20%), and Peripheral vision 3 (12%). Conclusions: For non-diplopic patients, the AS-20 is more responsive than the VFQ25 to improvement in HRQOL following strabismus surgery. For diplopic patients both questionnaires are responsive. The new strabismus-specific AS-20 questionnaire is useful over the entire spectrum of strabismus and addresses both function and psychosocial issues. CR: J.M. Holmes, None; S.R. Hatt, None; D.A. Leske, None. Support: NIH Grant EY015799 (JMH), Research to Prevent Blindness, Inc., and Mayo Foundation Purpose: To assess the long-term stability of improvements in symptoms and signs in 9- to 17-year-old children enrolled in the Convergence Insufficiency Treatment Trial who were asymptomatic after treatment for convergence insufficiency (CI). Methods: 79 patients who were asymptomatic after a 12-week therapy program for CI [33 in office-based vergence/accommodative therapy (OBVAT), 18 in home-based pencil push-ups (HBPP), 12 in home-based computer vergence/accommodative therapy and pencil push-ups (HBCVAT+), and 16 in office-based placebo therapy (OBPT)] were followed for 1 year. Maintenance therapy was prescribed for the first 6 months and no treatment for the second 6 months. Symptoms and clinical signs were measured 6 months and 1 year after completion of the 12-week therapy program. Outcome measures were the mean change on the Convergence Insufficiency Symptom Survey (CISS), near point of convergence (NPC), positive fusional vergence at near (PFV), and proportions of patients who remained asymptomatic on the CISS or who were classified as successful or improved based on a composite measure of CISS, NPC, and PFV. Results: 1-year follow-up visit completion rate was 89% (32/33 OBVAT, 15/18 HBPP, 10/12 HBCVAT+, and 13/16 OBPT) with no significant differences between groups (p = 0.26). Eight patients (10%) reported seeking alternative treatment subsequent to the completion of the 12-week therapy program but prior to the 1-year followup visit (1 OBVAT, 3 HBPP, 2 HBCVAT+, and 2 OBPT). Among the remaining 62 patients (31 OBVAT, 12 HBPP, 8 HBCVAT+, and 11 OBPT), there were no significant changes in the CISS, NPC, or PFV in any treatment group during the 1-year follow-up (p-values ≥ 0.077). Twenty-seven of the 32 patients (84%) in the OBVAT group remained asymptomatic and, using the composite measure, 87% remained either successful (56%) or improved (31%) 1-year post-treatment. Conclusions: Improvements in symptoms and clinical signs occurring after officebased vergence/accommodative therapy with home reinforcement are maintained in most children aged 9 to 17 years for at least 1 year after discontinuing treatment. CR: M. Scheiman, None; M. Kulp, None; G. Mitchell, None; S. Cotter, None; M. Rouse, None; R. Hertle, None. Support: U10 EY014713-01A2 CT: www.clinicaltrials.gov, NCT00338611 1206 - 9:00AM Residual Strabismus in Children Following Resolution of Cranial Nerve Palsies Affecting Ocular Motility 1207 - 9:15AM Accommodative and Vergence Responses to Conflicting Blur and Disparity Stimuli During Visual Development M.L. Bratton1A, M.E. Hoehn1B, N.C. Kerr1B. ACollege of Medicine, BDepartment of Ophthalmology, 1University of Tennessee, Memphis, TN. S.R. Bharadwaj, T.R. Candy. School of Optometry, Indiana Univ Bloomington, Bloomington, IN. Purpose: Children with cranial nerve palsies (CNP) are at risk for residual strabismus after their motility deficits resolve. We sought to evaluate if this was true for CNP secondary to a CNS malignancy. Methods: We identified 106 children with CN III, IV, and/or VI palsies who were treated for CNS malignancies. A retrospective chart review was conducted to determine the presence or absence of residual strabismus following resolution of motility deficits. Results: Forty-eight of 106 children resolved their motility deficits with treatment of their CNS malignancy. One child had a CN III palsy, 6 had CN IV palsies (one was bilateral), 40 patients had CN VI palsies (16 were bilateral), and one child had two different CNP in the same eye (CN IV and VI). Of the 48 children who resolved their motility deficits, 35 patients had residual strabismus (Group A). Only 13 resolved their strabismus (Group B). Average angle of strabismus before motility deficits resolved was 33.8 prism diopters (PD) in Group A and 20.6 PD in Group B (not a statistically significant difference). There was no significant difference between Group A and B with regards to age at diagnosis or length of follow-up. Conclusions: Our findings indicate that the majority of children with resolved motility deficits from a CNP after treatment for CNS malignancy will be left with residual strabismus, regardless of age at diagnosis, angle of strabismus at presentation, or type of CNP. Children with CNP secondary to CNS malignancy need ophthalmic care after motility deficits resolve, as they are likely to have residual strabismus, which can put the child at risk for visual system problems related to loss of binocularity, including amblyopia. CR: M.L. Bratton, None; M.E. Hoehn, None; N.C. Kerr, None. Support: None Purpose: Clear and single vision requires coordinated accommodation and vergence motor responses. The accommodative demand of infants is typically greater than that of adults due to hyperopia, while their vergence demand is smaller due to reduced inter-pupillary distance. The relationship between these demands also changes with growth of the eye and head, requiring some form of flexibility in the interaction between accommodation and vergence to maintain clear and single vision. Here, we assessed the capacity of the developing visual system to overcome short-term experimentally induced conflicts between accommodation and vergence demands. Methods: Accommodative and vergence responses were measured using a PowerRefractor (25Hz). 101 subjects (2.0months to 40.1years) experienced binocular step changes in either blur (-2D lenses) or disparity (2MA base-out prisms) while they watched a high contrast cartoon movie at 80cms. 14 and 12 subjects also experienced 1D or MA and 3D or MA step changes in blur and disparity demands, respectively. The strengths of accommodation-vergence cross-coupling (AC/A and CA/C ratios) was also measured in 38 and 20 subjects respectively (3.2months to 11.1years) under conditions of open-loop disparity and blur cues. Results: The frequency of response to both lenses and prisms increased significantly with age (p<0.001), with no significant difference between lenses and prisms (p=0.38). The direct response gain (i.e. accommodation to lenses and vergence to prisms) increased significantly with age (p<0.001), with a slightly but significantly larger response to prisms (Mean+/-SEM: 0.71+/-0.02) than to lenses (0.58+/-0.02) at all ages (p<0.001). Across all ages (p=0.52), the coupled response gain (i.e. vergence to lenses and accommodation to prisms) was much smaller for both lenses (0.10+/-0.01) and prisms (0.17+/-0.03) and they were significantly smaller than (p<0.001) and poorly correlated with the subject’s AC/A (r=0.25) and CA/C (r=0.21) ratios. Unlike response frequency (p=0.14) and coupled response gain (p=0.73), the direct response gain decreased significantly with increased stimulus demand for both lenses and prisms (both p<0.001). Conclusions: The typically developing visual system can, at least partially, compensate for conflicts in blur and disparity demands by independently modulating its accommodative and vergence responses, suggesting short-term flexibility in the interaction between the two motor systems. CR: S.R. Bharadwaj, None; T.R. Candy, None. Support: NIH Grant EY014460 (TRC) Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1204-1207 Monday, May 4, 8:30 AM - 10:15 AM Palm A Paper Session Program Number Range: 1204 - 1210 202. Strabismus I Organizing Section: EY 1208 - 9:30AM Defining the Critical Period for Smooth Pursuit Development in Infant Primates: Effects of Binocular Decorrelation 1209 - 9:45AM Prevalence of the Ocular Motor Signs of the Infantile Strabismus Complex in Children with and Without Cerebral Visual Pathway White Matter Injury K.T. Le1, P. Foeller2, D. Bradley3, L. Tychsen2, A.M. Wong1. 1Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 2Washington University in St. Louis, St. Louis, MO; 3Yerkes Regional Primate Research, Atlanta, GA. S. Khanna1A, A. Sharma1B, F. Ghasia1A, T. Inder1C, L. Tychsen1A. AOphthalmology, B Neuroradiology, CPediatrics, 1Washington University, St Louis, MO. Purpose: Infantile esotropia is typically associated with nasotemporal asymmetry of smooth pursuit, manifested as a bias favoring nasalward target motion when viewing monocularly. Earlier studies by our group have found that an optical strabismus induced in non-human primates during an early critical period of development causes smooth pursuit asymmetry when image decorrelation occurs between the first 3-12 weeks of life (equivalent of age 3-12 months in humans). The purpose of this study was to further delineate the critical period of smooth pursuit development. Methods: Binocular image decorrelation was imposed on infant macaques by fitting them with prism goggles on day 1 of life. The goggles were removed after 3 (n=2), 6 (n=2), 9 (n=2) or 12 weeks (n=3), emulating surgical repair of strabismus in humans at 3, 6, 9 and 12 months of age, respectively. Two control monkeys wore plano lenses. Several months after goggle removal, horizontal smooth pursuit was recorded using binocular search coils and a nasal-bias index (NBI) was calculated. Results: Each animal in the 9- and 12-week groups developed nasotemporal asymmetry of smooth pursuit when viewing with either eye. The smooth pursuit in 3- and 6-week duration monkeys was symmetric and indistinguishable from the controls. NBI were negligible or slightly negative in the control, 3- and 6-week monkeys, but positive and substantially greater (9-14x) in the 9-and 12-week monkeys (ANOVA, p<0.05). Conclusions: We further delineate the critical period of smooth pursuit development; it appears to occur between 6 and 9 weeks postnatally in monkeys. Our findings suggest that surgical repair of infantile esotropia in humans would be most beneficial before the age 6 months. CR: K.T. Le, None; P. Foeller, None; D. Bradley, None; L. Tychsen, None; A.M. Wong, None. Support: NIH Grant EY10214 (L.T.), Walt and Lilly Disney Award for Amblyopia Research from Research to Prevent Blindness (L.T.), Grant MOP 67104 (A.W.), CIHR New Investigator Award (A.W.) Purpose: To determine if the prevalence of the ocular motor signs of the infantile strabismus complex increases as a function of the severity and extent of cerebral visual pathway white matter injury (CVPWMI). CVP was defined as the posterior optic radiations and the splenium of the corpus callosum. Methods: MRIs obtained ≥ age 2 yrs were scored using a standardized system (CVPWMI graded 1-3) in 67 children (mean GA 31 wks; mean BW 1885 g) who had WMI detectable as periventricular leukomalacia with or without reduced volume of the splenium. Masked ophthalmologic and orthoptic examinations were performed on the CVPWMI group and a GA-matched control group who had normal MRIs. Results: Infantile strabismus (primary eso: exo 3.5:1) was documented in 60% of grade 1, 77% of grade 2, and 86% of grade 3 CVPWMI children, respectively. Other ocular motor signs of the complex increased with CVPWMI grades 1-3: latent/manifest latent nystagmus (20%; 47%; 46%), DVD (13%; 26%; 27%), and nasotemporal pursuit/ OKN asymmetry (13%; 37%, 37%). The prevalence of each of these signs in the control group was ≤ 8% (ANOVA and chi-square < 0.05). CVPWMI grade related also to the prevalence of retrograde (axial and sectoral) optic neuropathy (6%, 27%, 36%). Conclusions: Children who suffer CVPWMI develop the ocular motor signs of the infantile strabismus complex at rates substantially exceeding those of non-CVPWMI children. The prevalence of the signs increases with CVPWMI severity. These findings reinforce the conclusion that the infantile strabismus complex is caused by prenatal/ perinatal damage to cerebral visuomotor pathways. CR: S. Khanna, None; A. Sharma, None; F. Ghasia, None; T. Inder, None; L. Tychsen, None. Support: Gustav and Louise Pfeiffer Foundation Award (FG,LT) 1210 - 10:00AM Reduced Quality of Life in Childhood Intermittent Exotropia S.R. Hatt, D.A. Leske, T. Yamada, E.A. Bradley, J.M. Holmes. Department of Ophthalmology, Mayo Clinic, Rochester, MN. Purpose: To assess health related quality of life (HRQOL) in children with intermittent exotropia (IXT) and their parents. Methods: Individual interviews with children with IXT and one of their parents generated items for Child, Proxy (parental assessment of child’s HRQOL), and Parent questionnaires, which were then refined using standard item reduction methodology. Three final derived IXT questionnaires (IXTQ): Child, Proxy, and Parent (12, 12, and 17 items respectively) were administered to 33 children with IXT (median 8 years, range 5-15) and one of their parents, and 49 control children (median 8 years; range 5-13) and one of their parents. Children in the control group had no strabismus or amblyopia. A Likert type scale ranging from ‘never’ (score 100, best HRQOL) to ‘almost always’ (score 0, worst HRQOL) was used for responses. Wilcoxon tests were used to compare median scores between IXT and control groups. Results: Median Child IXTQ scores were significantly lower (worse HRQOL) in the IXT group compared with the control group: 85 (range 54-100) versus 92 (50-100); P=0.04. Median Proxy IXTQ scores were significantly lower for IXT children than controls: 83 (54-100) versus 98 (65-100); P<0.0001. The most discriminating questions for both Child and Proxy questionnaires related to shutting one eye in the sun and comments from others. Median Parent IXTQ scores were also significantly lower in the IXT group compared with the control group: 68 (range 24-100) versus 93 (49-100); P<0.0001. All Parent questions discriminated well between IXT and control groups, relating to possible surgery, psychosocial concerns, and function concerns of the child Conclusions: We have developed and validated a new 3-part patient-derived HRQOL questionnaire for children with IXT and their parents. These questionnaires detect reduced HRQOL in children with IXT both as reported by the child themselves and as perceived by their parents. Childhood IXT also affects the HRQOL of the parents. The IXTQ HRQOL questionnaires may prove useful in the clinical assessment of IXT and for clinical trials. CR: S.R. Hatt, None; D.A. Leske, None; T. Yamada, None; E.A. Bradley, None; J.M. Holmes, None. Support: NIH Grants EY015799 (JMH) and EY013844 (EAB), Research to Prevent Blindness, Inc., and Mayo Foundation Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1208-1210 Monday, May 4, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 1436 - 1447 / A326 - A337 222. Neuro-Ophthalmology: Treatment Organizing Section: EY 1436 - A326 Ocular Myasthenia Gravis: Treatment Successes and Failures in Patients With Long Term Follow Up 1437 - A327 Effect of Transcorneal Electrical Stimulation(tes) in Patients With Traumatic Optic Neuropathy(ton) M. Kurli1, M.J. Kupersmith1,2. 1Ophthalmology, New York Eye and Ear Infirmary, New York, NY; 2Institute of Neurology and Neurosurgery, Roosevelt Hospital, New York, NY. H. Shimojyo1A, T. Fujikado1B, T. Morimoto1A, Y. Okawa1B, K. Matsushita1A, Y. Kitaguti1B, Y. Tano1A. AOphthalmology, BApplied Visual Science, 1Osaka Univ Medical School, Suita, Japan. Purpose: We previously reported prednisone reduced the frequency of generalized myasthenia (GMG) and controlled diplopia, without major adverse effects at 2 years, in patients with ocular myasthenia gravis (OMG). Questions remain whether study subjects had long standing disease-biasing results towards a steroid benefit and if prednisone merely delayed GMG onset. Methods: Record review of a referral neuro-ophthalmology service OMG database for patients who had follow up > 4 years or until GMG developed. We studied the effect of prednisone on GMG incidence and control of ocular symptoms. Generally, patients with diplopia were recommended for prednisone therapy. Most remained on daily 2.5-10 mg to prevent diplopia. We compared the results for prednisone-treated and ‘untreated’ (pyridostigmine only) patients. Results: Of 87 patients, 55 were in the prednisone-treated and 32 were in the ‘untreated’ groups. GMG developed in 7 (13%) of prednisone-treated (OR 0.41; 95 % CI: 0.22, 0.76) and in 16 (50%) of ‘untreated’ (OR 2.78; 95% CI: 1.68, 4.60) patients. After OMG onset, GMG developed at a mean of 5.8 years and 0.22 years in prednisone and ‘untreated’ groups. Diplopia was present at the last exam in 27% of prednisone-treated (mean 7.2 years) and in 57% of ‘untreated’ (mean 4.6 years) OMG patients. For 48 prednisonetreated patients who did not develop GMG, OMG treatment failure occurred in 13. Conclusions: Prednisone delays the onset of GMG and has sustained benefit of reducing the incidence of GMG and controlling diplopia. Without prednisone, GMG develops in 50% of OMG patients, typically within 1 year. CR: M. Kurli, None; M.J. Kupersmith, None. Support: : Alice and Richard Netter, David B. Kriser Foundation, and Michael Fisher Foundation Purpose: To determine the effect of transcorneal electrical stimulation(TES) on the visual acuity of patients with traumatic optic neuropathy (TON). Methods: Consecutive twenty-six eyes of 26 patients with TON treated by TES in our hospital between 2004 and 2007 and were followed-up at least 2 months after the treatment were studied. We classified the patients into three groups by the visual acuity before treatment. Severe group, log minimum angle of resolution (logMAR)≥2, n=7, moderate group, 1≤logMAR<2, n=10, and mild group, logMAR<1, n=9. TES (650-1000 μA, 20 Hz, 30 minutes) was applied using a contact lens-type stimulating electrode. Followed-up period was 2 to 21 months (average, 7.1 months) We measured the visual acuity, the threshold current to evoke phosphene in the peripheral visual field (Th1),and the current to evoke phosphene in the central visual field (Th2). Results: The visual acuity improved equal or more than 0.3 logMAR units in 10 patients (1 in severe group. 6 in moderate group. 3 in mild group). The visual acuity did not worsen more than 0.3 logMAR units in any of the patients. Except for the severe group, visual acuity was significantly improved. (P=0.01 in moderate group and p=0.03 in mild group, Signed Rank Test). Th1 was significantly improved except for the severe group (P=0.01 in moderate group and p=0.03 in mild group). Threshhold of the central phosphene was significantly improved only in the mild group (p=0.016) . No side effect was observed except for a mild superficial keratopathy after TES. Conclusions: The visual acuity and the threshold current to evoke phosphene improved after TES in some patients with TON without major complications. The treatment effect may not be expected in severely injured cases (logMAR≥2). These results suggest that TES could be considered as a new treatment for eyes with mild to moderate TON. CR: H. Shimojyo, None; T. Fujikado, None; T. Morimoto, None; Y. Okawa, None; K. Matsushita, None; Y. Kitaguti, None; Y. Tano, None. Support: None 1438 - A328 Training Hemianopes in Their Blind Hemifield: Comparison of Two Left Hemianopes on Detection and Categorisation Tasks 1439 - A329 Visual Outcomes of Patients With Neuromyelitis Optica While Receiving Rituximab vs. Standard Treatment I. Gaudry1A, C. Cavezian1A, C. Perez1A, M. Obadia1B, O. Gout1B, S. Chokron1A. AERT TREAT Vision, BService de neurologie, 1Fondation Ophtalmologique Rothschild, Paris, France. M.S. Floyd, T.J. Whittaker. Ophthalmology, Kansas University Medical Center, Overland Park, KS. Purpose: Recovery from long lasting visual field defect after primary visual cortex injury has scarcely been reported. Recently, Chokron et al. (2008) described an enlargement of the visual field in adult hemianopes, after specialized rehabilitation based on blindsight theories. Methods: Following these same theories, we attempted to train high perceptual processes in the blind field of two left hemianopes through “active training” (i.e., a same/different judgement of two successive natural scene images, with feedback). RP had minimal sparing in his upper left visual field. ML had upper left minimal sparing on his right eye and lower-left minimal sparing on his left eye. As a control task, a “passive training” (i.e., colour frame judgement in the central visual field) was completed with a one-week delay from the active training. Training effects were evaluated in a categorization task of natural scene images and in a detection task of flashing dots. Both tasks were performed as pre- and post-training tests. In all tasks, stimuli were presented centrally or with a 3.5° eccentricity, and fixation was controlled with a video camera. In addition, the hemianopes performances were compared with 10 healthy controls. Results: The “active training” increased detection rates in the blind hemifield of both patients and showed slightly improved performance in the central-left visual field. Moreover patient ML showed higher detection rates for stimuli presented in the lower-left visual field but a lower detection rate for stimuli in the lower-right visual field. Patients performed similar to controls for upper left presentations. There was no improvement in categorization skills. Passive training did not lead to improvements. Conclusion: Although each training type was performed only once, detection capacities seem partially flexible in some patients. Compared to automated perimetry measures, our data suggest that attentional mechanisms could be redirected toward one hemifield in hemianopia. CR: I. Gaudry, None; C. Cavezian, None; C. Perez, None; M. Obadia, None; O. Gout, None; S. Chokron, None. Support: None Purpose: To compare the visual outcome of patients with Devic’s Disease who undergo treatment with Rituximab vs. other immune modulating treatment. Methods: A retrospective chart review was conducted on 12 eyes (6 patients) with Neuromyelitis Optica treated at Kansas University Medical Center. Patients were diagnosed by NMO IgG antibodies, or clinical history, examination, and imaging. Patients with multiple sclerosis, tumor, and cerebral vascular disease were excluded. Visual acuity and Humphrey visual fields at the initial visit, 1 month, 3 to 6 months, and 1 year were collected. Data recorded during relapses was avoided due to inconsistency. Medical treatment, relapse, and symptoms were documented. A statistically significant change in acuity was defined as 3 Snellen lines and visual field greater than 2 db. Results: Charts were reviewed from 2000 to 2008. The age range was 38 to 58. All patients except 1 were followed for at least 3 months. This patient had recently enrolled and is still being evaluated. 3 patients were diagnosed by NMO IgG and 3 clinically. All patients were treated initially with steroids. 1 patient was treated with only steroids, 1 with only rituximab, and 4 with other immune modulating drugs such as mycophenolate moxetil, methotrexate, and plaquenil (2 of these were then switched to rituximab). Visual acuity was stable at 1 year in 2 of 3 rituximab patients. One patient receiving Rituximab who experienced visual decline was experiencing loss prior to therapy. 2 of 3 patients in the non-Rituximab treatment group had a decline in acuity. The following is a list of complications: leg and arm dysarthria and paresthesia, urine retention, nausea, neck pain, and hospitalization. There were 24 relapses reported with an average of 1.7 per year. 79 % of episodes occurred during the spring and fall. Conclusions: Data from these patients indicate that Rituximab may be more effective than steroids and immune modulating drugs in treatment of visual acuity and visual field loss. There is no definitive trend regarding relapse rate between the groups. There may be a correlation between relapse and seasonal changes. This is a difficult group to study as medical records are imperfect because patients follow with multiple specialties and data is often obtained when the patient is having a relapse. These patients need to be followed for a longer duration and a larger sample size would be optimal. CR: M.S. Floyd, None; T.J. Whittaker, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1436-1439 Monday, May 4, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 1436 - 1447 / A326 - A337 222. Neuro-Ophthalmology: Treatment Organizing Section: EY 1440 - A330 Idebenone Treatment in Patients With Leber Hereditary Optic Neuropathy 1441 - A331 Long Term Follow-Up of Optic Nerve Sheath Decompression in Idiopathic Intracranial Hypertension J.G. Eng1,2, D. Aggarwal2, A.A. Sadun2. 1Department of Ophthalmology, University of South Carolina, Columbia, SC; 2Doheny Eye Institute/USC Keck School of Medicine, Los Angeles, CA. Purpose: To examine whether patients with Leber Hereditary Optic Neuropathy (LHON) may show improvement in vision after starting idebenone, a synthetic analog of Coenzyme Q10. Methods: 7 patients (6 males and 1 female) who took idebenone for LHON were selected for this study. Four patients had the 11778 mutation; one patient had the 3460 mutation; one patient had the 14484 mutation; the remaining patient had no mutation identified. These patients had visited the neuro-ophthalmology clinic at Doheny Eye Institute from 2003 to 2008. Charts were reviewed and evaluated for any improvement in visual acuity (VA), color vision, and Humphrey visual field after initiation of idebenone therapy. Results: Four patients experienced no improvement in visual acuity, color vision, or visual fields after taking idebenone. Three patients demonstrated a dramatic or marked improvement. A 50 year old female with the 11778 mutation had VA of 20/200 OU when starting idebenone 450 mg/day. VA improved to 20/50 OU in one month. When VA decreased to 20/400 OD and CF 2 ft OS three months later, idebenone was increased to 540 mg/day. At a follow-up visit six months later, VA had improved to 20/30 OD and 20/60 OS and visual fields showed complete clearing of central scotomas. Her color vision also improved from discerning 0/12 color plates OU prior to taking idebenone to 2/12 color plates OU. A 16 year old male with the 14484 mutation had progressive visual loss with VA 4/200 OD and 5/200 OS, bilateral central visual field defects, and color vision of 0/8 OD and 3/8 OS using AO test plates. He was started on idebenone 360 mg/day and over the course of 1.5 years, VA improved to 20/40 OD and 20/60 OS. Visual fields showed improvement in both eyes with a decrease in central depression OD and only a patchy central defect with preserved vision nasally OS. Patient could discern 8/14 plates OD and 6/14 plates OS. A 17 year old male with the 11778 mutation had VA of CF 4 ft OD and 20/400 OS and color vision of 0/8 plates OD and 4/8 plates OS. He was started on idebenone 360 mg/day and after two months, he experienced a modest improvement in VA OD to 20/200 with VA of 20/400 OS. He could also discern 9/20 OD and 8/20 OS H-R-R plates after 2 months of idebenone. This patient also experienced an improvement in his visual field. Conclusions: Some patients with LHON treated with idebenone showed marked improvement in visual acuity, color vision, and visual fields. Although prospective studies are needed to determine the role of idebenone in visual recovery, the relatively safe side effect profile of idebenone makes it a treatment option for many patients diagnosed with LHON. CR: J.G. Eng, None; D. Aggarwal, None; A.A. Sadun, None. Support: International Foundation for Optic Nerve Disease, Research to Prevent Blindness J.R. Shipp1, J. Corbett1, S. Kedar1, C. Willen2, M. Acierno3. 1Ophthalmology, University of Mississippi, Jackson, MS; 2Ophthalmology, University of Alabama, Birmingham, AL; 3Ophthalmology, Louisiana State University, New Orleans, LA. Purpose: To evaluate the long term visual outcomes of subjects having undergone optic nerve sheath decompression for the treatment of idiopathic intracranial hypertension. Methods: A retrospective chart review was performed on all patients who had undergone optic nerve sheath decompression between October 1994 and April 2006 at the University of Mississippi Medical Center and the University of AlabamaBirmingham Hospital. Surgeries performed for diagnoses other than IIH were excluded. Best-corrected visual acuity, color vision, optic disc appearance, and automated perimetry were recorded for the pre-operative period and each postoperative visit through January 2008. Results: We reviewed 100 cases of optic nerve sheath decompression in 75 patients. We categoried our findings into 3 groups based on the level of pre-operative visual acuity: (1) VA > 20/40 (2) VA = 20/50-20/200 (3) VA < 20/200. Of the 49 eyes in group 1, 43 eyes (88%) had a final visual acuity of 20/40 or better, 4 eyes (8%) had a final visual acuity of 20/50-20/200, and 2 eyes (4%) had a final visual acuity of less than 20/200. Of the 29 eyes in group 2, 10 eyes (34%) had a final visual acuity of 20/40 or better, 15 eyes (52%) had a final visual acuity of 20/50-20/200, and 4 eyes (14%) had a final visual acuity of less than 20/200. Of the 22 eyes in group 3, 2 eyes (9%) had a final visual acuity of 20/40 or better, 1 eyes (5%) had a final visual acuity of 20/50-20/200, and 19 eyes (86%) had a final visual acuity of less than 20/200. Of all cases taken together, 81 eyes (81%) showed improvement or stabilization of their visual acuity. Mean and pattern standard deviations on automated perimetry showed a trend toward improvement, color vision remained stable, and disc appearance evolved from edematous (96%) initially to pallor (58%) at final visit. Conclusions: Optic nerve sheath decompression in the treatment of idiopathic intracranial hypertension tends to stabilize patients in the long term. Visual prognosis is better in patients with good visual acuities initially. Patients with poor visual acuities initially tended to retain poor visual acuities. Consideration should be given to earlier surgical intervention in IIH before visual acuity is signicantly affected. CR: J.R. Shipp, None; J. Corbett, None; S. Kedar, None; C. Willen, None; M. Acierno, None. Support: None 1442 - A332 Optic Nerve Sheath Fenestration With a Raman-Shifted Mid-Infrared Laser (Tissue Study) 1443 - A333 Long-Term Outcomes for the Mouse Eye with AAV Mediated Gene Delivery of the Human ND4 Complex I Subunit J. Shen1A, J. Kozub1B, R. Prasad1A, K. Joos1A. AOphthalmology, BFree Electron Laser Center, 1Vanderbilt University, Nashville, TN. X. Qi1A, A. Lewin1B, W. Hauswirth1A, J. Guy2. AOphthalmology, BMolecular Genetics and Microbiology, 1University of Florida, Gainesville, FL; 2Ophthalmology, University of Miami, Miami, FL. Purpose: Optic nerve sheath fenestration is a treatment for vision loss in idiopathic intracranial hypertension not responding to medical management. Our previous studies suggest that endoscopic application with Free Electron Laser energy at 6.1 μm may be useful for minimally invasive orbital therapy including optic nerve sheath fenestration. This study proposes to make this technique more clinically feasible with substitution of a portable laser for the cost-prohibitive experimental Free Electron Laser (FEL). Methods: The laser proposed for this study is a Q-switched, tunable alexandrite laser system, which provides a high-intensity, Q-switched output pulse of 50-100 ns at 10 pulses per second (Light Age, Inc.). It is wavelength-shifted by a two-stage stimulated Raman conversion process into the 6-7 μm range. Ten fresh cadaver porcine optic nerves were lased with 6.1 μm at 0.6 mJ with a 100 μm diameter spot. Besides linear incisions, a circular pattern was cut and the incised piece removed to form an optic nerve sheath window. Specimens were examined grossly and prepared for histological examination. Results: The table-top laser has a nearly Gaussian output and a narrow spectrum at 6.1 μm. The laser was capable of continuously incising the cadaver porcine optic nerve sheaths. Minimal thermal damage was evident. Conclusions: A Q-switched, Raman-shifted tunable alexandrite laser system is capable of providing the parameters necessary for incision of an optic nerve sheath. This portable system will provide the translational advancement necessary to bring endoscopic laser surgery closer to clinical usefulness. CR: J. Shen, None; J. Kozub, None; R. Prasad, None; K. Joos, None. Support: AFSOR – DOD FA9550-04-1-0045, NEI Core Grant EY08126-18, Unrestricted Departmental Grant from Research to Prevent Blindness, Inc., NY; Joseph Ellis Family Research Fund. Purpose: To evaluate the long-term effects of AAV mediated allotopic gene expression of a normal human ND4 (wt-ND4) of complex I subunit in the mouse visual system. Methods: wt-ND4 was made compatible with the universal genetic code and a mitochondrial targeting sequence (ATPc) was appended to the N terminus and an epitope (FLAG) added to the C terminus. This construct was packaged into AAV2 capsids. AAV containing wt-ND4, mutant (R340H) ND4 (mut-ND4), and GFP were intravitreously injected into the mice eyes. One year later, gene expression and potential toxicities were assessed by fluorescence, light and electron microscopy. Results: One year after the gene inoculation fluorescence microscopy revealed 15.0% FLAG positive and 5.3% GFP-positive retinal ganglion cells (RGC) in flat mounted retina of AAVwt-ND4 injected eyes, relative to the mean number of RGCs. The level of AAV-mut-ND4 gene expression was similar that the FLAG positive RGCs was 16.0% and GFP-positive RGCs was 5.4%. AAV- wt-ND4 inoculated retina had mean RGC of 3100+142 cells/mm 2, a 3.5 % less than the normal untreated eyes with mean of 3314+138 cells/mm 2, p>0.05. In contrast, AAVmut-ND4 caused 40% loss of RGC with mean of 1956+143 cells/mm 2, p<0.01. Morophometric analysis revealed that AAV-GFP inoculation caused 7% bigger in area of optic nerve head (ONH) relative to normal eyes, p>0.05. AAV-wt-ND4 gene inoculation showed the ONH swelling by 14%, p>0.05. AAV-mut-ND4 inoculation caused optic head swelling by 30 %, p<0.05. In the retrobulbar optic nerve cellular infiltration was increased almost two-fold (p < 0.01) in mut-ND4 treated eyes as compared to normal eyes. Delivery of the AAV- wtND4 or GFP did not change the cellular infiltration. To detect any demyelination in the retrobulbar optic nerve, the area of axonal myelin fiber was measured. As compared to normal eyes, AAV- wtND4 or GFP decreased the area of axonal myelin fiber by 3-5%, both p>0.05. The mut-ND4 inoculation caused axonal myelin fiber thinner by 36% (p<0.01), meaning the loss of myelin. Counting the number of axons, in contrast to the normal untreated eyes, AAV-GFP or wt-ND4 decreased the axons by 5% or 9%, respectively, both p>0.05. The severe loss of axons was evident after mut-ND4 gene inoculation, caused 41% loss of axons (p<0.01). Conclusions: A nuclear-encoded, importable version of wt-ND4 delivered by AAV2 can be detected one year after gene transfer. Expression of normal human ND4 in murine did not induce significant loss of RGCs and the axonal demyelination suggesting it may safe for treatment of LHON. CR: X. Qi, None; A. Lewin, None; W. Hauswirth, None; J. Guy, None. Support: RO1EY017141, Department RPB Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1440-1443 Monday, May 4, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 1436 - 1447 / A326 - A337 222. Neuro-Ophthalmology: Treatment Organizing Section: EY 1444 - A334 Restoration of Electroretinogram Activity in Exenterated Swine Eyes Following Ophthalmic Artery Anastomosis D. Ellenberg, J. Shi, H. Qian, S. Jain, J.-H. Chang, D.T. Azar. Ophthalmology, University of Illinois at Chicago (UIC), Chicago, IL. 1445 - A335 Effects of Corticosteroids in Experimental Optic Neuritis M. Dutt1, P. Tabuena2, E. Ventura2, A. Rostami2, K. Shindler1. 1Ophthalmology, University of Pennsylvania, Philadelphia,, PA; 2Neurology, Thomas Jefferson University, Philadelphia,, PA. Purpose: To determine the feasibility of restoring electroretinogram (ERG) activity of exenterated swine eyes following in vivo arterial anastomosis. Methods: The carotid artery was exposed and cannulated. The eye was exenterated along with the extraocular muscles and surrounding connective tissue. The ophthalmic artery was then identified and anastomosed to the carotid artery. Perfusion was confirmed by injecting FITC-conjugated tomato lectin into the anastomotic tubing and performing confocal microscopy of retinal flat-mounts. Dark-adapted ERG and optic nerve responses were analyzed to assess retinal function, and dilated eye examination and retinal imaging were performed. Results: Arterial anastomosis resulted in perfusion of blood from the carotid artery through the anastomosis and into the ophthalmic artery. Arterial perfusion was confirmed by the presence of tomato lectin-stained retinal vessels. Immediately following the anastomosis, ERG and optic nerve activity was minimal. However, an “a” wave (representing photoreceptor activity), “b” wave (representing bipolar cell activity), and optic nerve responses (representing RGC activity) were detected at 30 min after reperfusion. Conclusions: Electroretinographic function is restored following re-anastomosis of exenterated swine eyes. CR: D. Ellenberg, None; J. Shi, None; H. Qian, None; S. Jain, None; J.-H. Chang, None; D.T. Azar, None. Support: Supported by NIH P30-001792 (DTA) and an unrestricted departmental support from Research to Prevent Blindness (New York, NY) Purpose: Optic neuritis (ON) occurs with a high incidence in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). ON begins 9 days after immunization to induce EAE. Significant retinal ganglion cell (RGC) loss occurs in eyes with ON and is not detected until 14 days after immunization, suggesting that loss of RGCs is secondary to optic nerve inflammation. Treatment with corticosteroids suppresses RGC loss if administered daily beginning from day of immunization (d0) prior to disease onset. Our aim was to determine whether corticosteroid treatment is also effective at a clinically relevant time point after inflammation of the optic nerve begins. Methods: Stereotactic surgery with Fluorogold was used to retrogradely label RGCs. Proteolipid protein peptide 139-151 was injected to induce EAE and mice were scored daily for clinical EAE on a 5 point scale. Mice were treated daily from d0 to d14 or d10 to d14 with 200 mg/kg subcutaneous dexamethasone (dex), 20 mg/kg intraperitoneal methylprednisolone (MP) or PBS (control). Fluorescence microscopy was used to count labeled RGCs in retinal mounts and H&E staining was used to identify inflammatory infiltrates in the optic nerves. Results: Corticosteroid treatment from d0 to d14 almost completely blocked EAE, where PBS-treated mice developed typical EAE with an average score of 1.5 by d14. Less than 5% of eyes had ON when treated with dex from d0-d14 compared to more than 60% when treated with PBS and dex-treated eyes had significantly increased (>30%) RGC survival. Treatment with either dex or MP from d10-d14 led to only partial suppression of clinical EAE. Corticosteroid treatment beginning from d10 did not significantly reduce the presence of optic nerve inflammation at d14 or 18, nor did it enhance survival of RGCs. Conclusions: These experiments indicate that corticosteroid treatment in EAE mice initiated after inflammation has begun is not as effective when administered before the onset of ON. This is consistent with clinical outcomes in ON patients where MP treatment does not affect final visual outcome. This model can be used to evaluate potential alternative therapies to prevent RGC loss and permanent vision loss from ON. CR: M. Dutt, None; P. Tabuena, None; E. Ventura, None; A. Rostami, None; K. Shindler, None. Support: NIH/ NEI grant no. KO8EY15098, Career Development Award from RPB, F.M. Kirby Foundation 1446 - A336 Involvement of Trx1 in Protective Effect of 17β-Estradiol Against TNF-αInduced Axonal and Cell Body Degeneration 1447 - A337 Neuroprotective Effect of Ciliary Neurotrophic Factor (CNTF) in a Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy Y. Kitaoka, Y. Munemasa, Y. Hayashi, S. Ueno. Ophthalmology, St Marianna University School of Med, Kawasaki, Japan. M.K. Mathews1, A. Hunter, III 2, S.L. Bernstein1. 1Ophthalmology, University of Maryland, Baltimore, MD; 2Ophthalmology, University of Pennsylvania, Philadelphia, PA. Purpose: To examine the effect of 17β-estradiol (E2) on the level of Trx1 in TNF-αinduced optic nerve degeneration. To evaluate the role of Trx1 in protective effect of E2 on RGC-5 cell death induced by TNF-α. Methods: Eight-week-old female Wistar rats were divided into sham operated and ovariectomized (OVX) groups. The OVX rats were treated with either solvent vehicle or E2 subcutaneous implant immediately after ovariectomy. At 14 days post-operation, all rats were received intravitreal injection of 10 ng TNF-α or PBS. The eyes were enucleated 1, 7, or 14 days after intravitreal injection. Furthermore, RGC-5 cell (gift from N. Agarwal) viability was tested after exposure to 10, 50, or 100ng/ml TNF-α with or without glutamate. The effects of E2 (1 or 10 μM) and Trx1 siRNA were also evaluated. The expression of Trx1 in optic nerve or RGC-5 cells was examined by Western blot analysis. The localization of Trx1 in optic nerve cross section as well as transverse section was evaluated by immunohistochemistry. Results: Immunohistochemistry showed the substantial co-localization of Trx1 and neurofilament in the optic nerve. Morphometric analysis showed that E2 implantation significantly ameliorated TNF-α-induced axon loss. The level of Trx1 in the optic nerve was increased with E2 implantation. Cell viability assay showed that E2 treatment significantly improved the death of RGC-5 cells induced by TNF-α and glutamate. This ameliorated effect was significantly inhibited by Trx1 siRNA transfection. The level of Trx1 in the RGC-5 cell was significantly increased with E2 treatment and this increase was ameliorated by Trx1 siRNA. Conclusions: E2 can exert axonal and cell body protection against TNF-α-induced neurodegeneration with possible involvement of Trx1. CR: Y. Kitaoka, None; Y. Munemasa, None; Y. Hayashi, None; S. Ueno, None. Support: This work was supported by Grant-in-Aid No. 20791285 (YK) from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government; Uehara Memorial Foundation Purpose: To determine whether Ciliary Neurotrophic Factor (CNTF) exerts a neuroprotective effect in a mouse model of Anterior Ischemic Optic Neuropathy (AION) - rodent-AION (rAION). Methods: Male transgenic mice with the Thy-1 promoter, linked to cyan fluorescent protein (CFP) reporter ((Thy-1 (CFP) mice), (28-44g) were anesthetized, and AION was induced using a previously described experimental method - rodent AION (rAION) (1). Then one eye of each animal received an intravitreal injection of 0.75μg Ciliary Neurotrophic Factor (CNTF), which has been widely shown to protect retinal ganglion cells after injury (2). Controls included both sham-injected and untreated animals. Sham-injections consisted of 0.01 ml PBS intravitreally. On day 14, the animals were sacrificed by Co2- anesthesia and subsequent cervical dislocation; Eyes were enucleated, and fixed in 4% paraformaldehyde-PBS. Anterior chambers were removed; The retina was dissected out of the eye cup and mounted on microscope slides. CFP- fluorescent retinal ganglion cells (RGC’s) were imaged using confocal microscopy. The amount of RGC loss was determined by averaging the number of RGC’s counted in 12 randomly selected 200μ2 fields in each retina (400x magnification). Average RGC numbers and standard deviations were calculated using the Student’s t-test. The percentage of lost RGC’s was calculated for each treatment group. Results: After rAION induction, eyes treated with PBS only lost 55.7% of RGC’s when compared to controls. The CNTF- treated eyes lost an average of 36.8% of RGC’s when compared to controls. Therfore, CNTF injection resulted in an 18.9% decrease of RGC loss, when compared to PBS after rAION induction. Conclusions: The rodent model of AION and neuroprotection mimicks the actual clinical events in AION by selectively targeting the vasculature of the optic nerve head. Introduction of the neuroprotective factor after the ischemic event models the sequence of clinical disease followed by intervention more accurately than if CNTF were introduced in the eye before induction of ischemia. Preliminary data indicate that CNTF exerts a neuroprotective effect in sudden optic nerve ischemia. This model enables evaluation of neuroprotective factors in clinical post-stroke treatment in ischemic optic neuropathy. References: 1. Goldberg-Cohen, N Guo Y, et al. IOVS 2005; 46: 2716-2725 2. Mey J, Thanos S. Brain Res. 1993; 602: 304-317 CR: M.K. Mathews, None; A. Hunter, III, None; S.L. Bernstein, None. Support: NIH Grant EY015304 (SLB) Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1444-1447 Monday, May 4, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 1979 - 1998 / D754 - D773 264. Strabismus II Organizing Section: EY 1979 - D754 Clinical Application of a Digital Head Posture Measuring System for Pediatric Patients E.S. Hald1A, R.W. Hertle1B, D. Yang1B. AOphthalmology/Bioengineering, B Ophthalmology, 1University of Pittsburgh, Pittsburgh, PA. 1980 - D755 Sensitivity Analysis for Strabismus Measurements Using Corneal Reflections E.B. Geukers1, S. Schutte1, P.P. Jonker1, B.A.J. Lenseigne1, F.C.T. van der Helm1, H.J. Simonsz2. 1Biomechanical Engineering, TU Delft, Delft, Netherlands; 2Erasmus Medical Center, Rotterdam, Netherlands. Purpose: We have developed a digital head posture measuring system (DHP) and previously reported its validity tested with an artificial head and normal subjects in 3D positions (Yang, et. al 2007, Hald, et. al 2008). Now, we report its repeatability and accuracy of measurements performed in pediatric patients. Methods: All testing was performed with IRB approval. The DHP consists of a headmounted electronic compass, a standard PC, and customized software to sample and display 3D head posture in real time. It is mounted on a wire frame, similar to eyeglass frames. For repeatability tests (10 subjects), patient was instructed to view an image at a distance of 170 mm. The device was calibrated to zero when the patient reached their anomalous head posture. The patient’s head was then manually moved to the true zero position in 3D space by the investigator, and values for simultaneous yaw, pitch, and roll were sampled. Accuracy tests (5 subjects) involved the same basic procedure as repeatability tests but included the addition of a manual head posture measuring device (MHP) to calculate actual angle of measurement for statistical comparison (Yang, et. al 2007, Hald, et. al 2008). Repeatability values were found for repeatability tests and accuracy data were analyzed using a matched paired t-test to determine if differences between MHP and DHP angles are significant. Results: The DHP showed consistent outcomes compared with the MHP. Four subjects displayed pitch head postures, five displayed yaw head postures, and one displayed roll head postures. Match pairs t-tests for the difference between MHP and DHP head posture angles showed no significant difference between MHP and DHP angles for pitch, yaw and roll head postures (p > 0.05 for all three). Seven of the repeatability test subjects displayed noticeable yaw head postures, two displayed pitch head postures and three displayed roll head postures. After removing high and low angles from each subject’s data set, pitch subjects yielded 95% repeatability values ranging from 6-14 degrees. Yaw and roll subjects yielded repeatability values ranging from 3-23 degrees and 4-17 degrees, respectively. Conclusion: The repeatability and accuracy of the measurements with DHP was supportive for the use of the DHP on pediatric patients. With additional patient testing and improvement of measurement procedures, the DHP will be a valid device to repeatedly measure head posture in 3D. CR: E.S. Hald, None; R.W. Hertle, None; D. Yang, None. Support: Fight For Sight Summer Studentship Purpose: The reoperation rate of strabismus surgery is about 20%. The main determinant for the amount of muscle relocation is the preoperative angle of strabismus. Currently, the Prism Cover Test (PCT) is the golden standard to measure strabismus angles. Drawbacks of PCT include the limited precision, the required time and required cooperation level. Accordingly, there is potential for a more accurate and quicker strabismus measurement device. A potential principle for this device is the IR eye tracking technique of measuring the corneal reflection relative to the corneal center. Methods: The sensitivity of the method of measuring angles of strabismus using the corneal reflection relative to the corneal center was investigated in relation to a patient’s biometric parameters and the geometry of the measurement setup. A 2D model was made of the setup and the anatomy of the eye according to Gullstrand’s eye model (Le Grand and El Hage, 1980). The sensitivity of the measurement method to variations (mean ± 2SD) in the corneal radius (Rc), the anterior chamber depth (ACD), the interpupillary distance (IPD) and the distance (d) and rotation (α) of the head with respect to the experimental setup were investigated. Results: Strabismus angles were determined theoretically using relative distances between the calculated corneal reflection and corneal center in the 2D model. The corneal reflection method was sensitive to Rc (± 5% for 7.8 ± 0.6mm), ACD (± 16% for 3.2 ± 0.8mm) and to head rotation α (± 4% for 0 ± 10°). Measurement accuracy was affected little by the head distance d (± 0.2% for 1000 ± 100 mm) and IPD (± 0.1% for 60 ± 20 mm). Conclusions: In a strabismus measurement device, the patient’s Rc, ACD and head rotation with respect to the camera should be accounted for, as these parameters have a significant influence on the measurement accuracy. The IPD and the head distance from the patient to the experimental setup can be neglected. CR: E.B. Geukers, None; S. Schutte, None; P.P. Jonker, None; B.A.J. Lenseigne, None; F.C.T. van der Helm, None; H.J. Simonsz, None. Support: None 1981 - D756 Graves Ophthalmopathy - Predictors of Diplopia 1982 - D757 Binocular Interactions in Human Strabismus: A Multifocal VEP Study W.E. Adams1, H. Haggerty2, J. Dickinson2, A. Coulthard 3. 1Ophthalmology, Sunderland Eye Infirmary, Sunderland, United Kingdom; 2Ophthalmology, Royal Victoria Infirmary, Newcastle Upon Tyne, United Kingdom; 3Radiology, Royal Brisbane and Women’s Hospital, Brisbane, Australia. H. Cheng, B. Zhang, K. Wicks, Y. Chino. College of Optometry, University of Houston, Houston, TX. Purpose: Patients with Graves Ophthalmopathy (GO) frequently experience diplopia due to restrictive myopathy. Some investigators have suggested that the MRI measurements of extraocular muscle volume can be used to predict ocular motility and diplopia. We compared muscle volumes and uniocular fields of fixation (UFOF) to the field of binocular single vision (BSV). Methods: 24 patients with GO were evaluated by plotting a field of BSV on the Goldmann perimeter and scored from 0 (constant diplopia) to 100 (no diplopia). UFOF were plotted for each eye along 6 muscle axes. Muscle volumes were measured from 3-D MRI images. UFOF measurements and muscle volumes were compared between the 12 patients with significant diplopia (BSV score <80) and the 12 without significant diplopia (BSV>80). Results: The patients with diplopia had lower UFOF scores for 7 of 8 muscles compared to those without diplopia (Right Medial Rectus 37.0 deg vs 48.2, R Lateral Rectus 32.1 vs 42.8, R Inferior Rectus 19.9 vs 32.5, R Superior Rectus 44.7 vs 55.5, Left Medial Rectus 37.9 vs 47.7, L Lateral Rectus 34.3 vs 43.3, L Inferior Rectus 25.1 vs 33.9, p < 0.01 for all comparisons). Only the UFOF of the LSR was borderline significantly different (47.6 deg vs 54.7, p=0.06). In contrast, individual muscle volumes (mm3 ) although numerically larger in patients with severe diplopia, were statistically similar (RMR 938.8 vs 836.8, RLR 809.4 vs 705.8, RIR 1050.3 vs 948.9, RSR 1185.8 vs 874.2, LMR 1066.6 vs 895.8, LLR 788.3 vs 672.6, LIR 1078.0 vs 846.5, LSR 1182.3 vs 874.3, all comparisons p>0.05). Total muscle volumes and total orbital volumes were also similar (8075.5 +/- 2632.7 vs 6671.2 +/- 1904.9, p= 0.1 and 41298.3 +/- 9140.9 vs 37405.3 +/- 8776.0, p=0.3 respectively). Conclusions: Diplopia in GO is strongly associated with reductions of individual muscle ductions, but this association is not paralleled by significant differences in muscle volumes. MRI cannot be used to predict motility and diplopia, and restriction should be assessed by clinical methods such as UFOF and BSV. CR: W.E. Adams, None; H. Haggerty, None; J. Dickinson, None; A. Coulthard, None. Support: None Purpose: To study the characteristics of binocular interactions in human strabismus Methods: MfVEPs were recorded in 17 normal and 8 strabismic subjects with a 60-sector pattern-reversal dartboard stimulus (VERIS). Normal subjects were tested under 3 viewing conditions: 1) monocular 2) bi-foveal and 3) diplopic. Strabismic subjects were tested under conditions 1) and 2), and their natural viewing condition. A haploscope coupled with an alternating cover test was used to achieve bi-foveal or diplopic conditions. Response amplitude (amp) was the root-mean-square amplitude in the signal window. Binocular interaction was assessed by a binocular-monocular ratio (BMR) averaged over 60 sectors, and BMR for each sector was the ratio of a sector’s amp under two-eye viewing condition to the better monocular amp at that sector, and expressed in dB. Results: Normal subjects showed binocular summation (BMR>0) under bi-foveal condition and binocular inhibition (BMR<0) under diplopic condition for all eccentricities with a mean BMR±SD of 0.47±0.46 dB and -1.47±0.74 dB, respectively. All strabismic subjects tested under natural viewing condition and 7 under bi-foveal condition reported single vision (presumably due to clinical suppression), and no binocular inhibition was observed for bi-foveal (mean BMR: 0.82±0.60 dB) or natural viewing (mean BMR: 1.07±0.61 dB) conditions. One subject couldn’t achieve bi-foveal viewing due to horror fusionis. He noted diplopia when targets were brought as close as possible to his foveas and showed inhibition under this condition (BMR = -1.21 dB). Another strabismic subject could see single or double under natural viewing condition. Her BMR was 1.03 dB and -0.64 dB under single and diplopic conditions. Conclusions: At the onset of strabismus (hence diplopia), V1 cortical physiology is likely to be dominated by inhibitory binocular interactions. However, since binocular inhibition could be demonstrated in our strabismic (and normal) subjects only under diplopic conditions and mfVEP signals are known to largely reflect the activity of V1 neurons, the neural mechanisms underlying clinical suppression in strabismic humans appear to reside beyond V1. CR: H. Cheng, None; B. Zhang, None; K. Wicks, None; Y. Chino, None. Support: NIH grants EY08128, P30 EY07551, T35EY0788, and Benedict-McFadden Professorship to YC Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1979-1982 Monday, May 4, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 1979 - 1998 / D754 - D773 264. Strabismus II Organizing Section: EY 1983 - D758 Prevalence of Strabismus and Amblyopia in Singapore Chinese Children: The Strabismus, Amblyopia and Refractive Error in Singaporean Children (STARS) Study M. Dirani1, A. Chia2, G. Gazzard 3, Y. Chan4, P. Selvaraj5, T.L. Young6, P. Mitchell7, T.Y. Wong1, S. Saw5. 1Ophthalmology, Centre for Eye Research Australia, Melbourne, Australia; 2 Ophthalmology, Department of Ophthalmology, Singapore National Eye Center, Singapore, Republic of Singapore, Singapore, Singapore; 3Ophthalmology, Glaucoma Research Unit, Moorfields Eye Hospital, United Kingdom., Moorfields, United Kingdom; 4 Statistics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 5Community, Occupational and Family Medicine, Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore, Republic of Singapore, Singapore, Singapore; 6Ophthalmology, Department of Ophthalmology, Duke University Medical Center, Durham, NC, Durham, NC; 7 Ophthalmology, Dept of Ophthalmology, University of Sydney, Australia., Sydney, Australia. Purpose: To determine the prevalence of strabismus and amblyopia in Singapore Chinese children aged 6 to 72 months. Methods: A population based survey was undertaken in the South-Western region of Singapore. Disproportionate random sampling by 6 month age groups was performed. Children underwent an Orthoptic assessment and cycloplegic (3 drops of cyclopentolate at 5 minute intervals) refraction using a table-mounted autorefractor in children older than 24 months, or a hand-held autorefractor in children aged 24 months or older, or streak retinoscopy if autorefraction failed. LogMAR Visual acuity was tested in children aged 30 months or older. If amblyopia was suspected (two line difference in visual acuity), visual acuity was re-tested. Results: 3009 children were recruited (participation rate = 72.3%), of which 3004 were analysed. The prevalence of strabismus in children (6 to 72 months) was 0.84% (95% Confidence Interval, CI: 0.80%-1.19%). Prevalence increased from 0.56% to 0.96% between ages 6 to 36 months and 37 to 72 months, but this was not significant (p=0.23) and there were no gender difference (p=0.54). Exotropia (20/24, 83.3%) was the most common strabismus, followed by Esotropia (3/24, 12.5%). The prevalence of amblyopia in children aged between 30 to 72 months was 1.87% (95% CI 1.81-1.94). There were no significant age and gender differences (p = 0.17). Amblyopia was attributed to refractive error alone in 72%, combined refraction/ strabismus in 23%, and strabismus alone in 5%. Refractive causes of amblyopia included astigmatism (59%), high hyperopia (20%), and myopia (14%). Conclusions: The prevalence of Strabismus and Amblyopia in preschool Singaporean Chinese children was low. Exotropia was the most common strabismus and astigmatism was the main determinant of amblyopia. CR: M. Dirani, None; A. Chia, None; G. Gazzard, None; Y. Chan, None; P. Selvaraj, None; T.L. Young, None; P. Mitchell, None; T.Y. Wong, None; S. Saw, None. Support: None 1984 - D759 Defining the Critical Period for Eye Alignment Development in Infant Primates: Effects of Binocular Decorrelation K. Lam1, P. Foeller2, D. Bradley3, L. Tychsen2, A.M. Wong1. 1Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 2Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO; 3Yerkes Regional Primate Research Center, Atlanta, GA. Purpose: Earlier studies by our group have found that an optical strabismus induced in non-human primates at birth causes a permanent large-angle esotropia when image decorrelation occurs between the first 3-12 weeks of life (equivalent of age 3-12 months in humans). The purpose of this study was to further delineate the critical period of eye alignment development. Methods: Binocular image decorrelation was imposed on 12 normal infant macaques (Macaca mulatta) by fitting them with prism goggles on day 1 of life. The goggles were removed after 3 (n=2), 6 (n=2), 9 (n=2), 12 (n=3), or 24 weeks (n=3), emulating surgical repair of strabismus in humans at 3, 6, 9, 12, and 24 months of age, respectively. Two monkeys wore plano lenses and served as controls. Several months after the goggles were removed, eye alignment was recorded using binocular search coils during automated single and alternate-cover testing. Alignment in each cardinal position was measured during steady fixation to assess concomitance. Results: The longer the duration of image decorrelation, the greater the magnitude of resultant concomitant esotropia. Only physiological (< 2 deg) heterophorias were detected in the control, 3-wk and 6-wk-duration groups. The 9-wk, 12-wk, and 24-wkduration monkeys exhibited larger-angle estropias (9 - 12 deg). Conclusions: Longer durations of binocular decorrelation in infancy cause greater maldevelopment of the vergence system manifested as larger-angle esotropia. Our findings suggest that surgical repair in infantile esotropia in humans would be most beneficial before the age of 6 months, and supports early correction of infantile strabismus. CR: K. Lam, None; P. Foeller, None; D. Bradley, None; L. Tychsen, None; A.M. Wong, None. Support: NIH EY10214, and Walt and Lilly Disney Award for Amblyopia Research from Research to Prevent Blindness 1985 - D760 Functional MRI in Macaque Monkey With Infantile Strabismus: Nasotemporal Motion Processing and Eye Tracking 1986 - D761 The Effect of Spectacle Wear on Health Related Quality of Life Measured Using the Intermittent Exotropia Questionnaire W. Bentley1A, L. Snyder1A, S. Petersen1B, P. Foeller1C, L. Tychsen1D. AAnatomy & Neurobiology, BNeurology, COphthalmology & Visual Sciences, DOphthalmology & Visual Sciences, Anatomy & Neurobiology, 1Washington University School of Medicine, St. Louis, MO. T. Yamada, S.R. Hatt, D.A. Leske, J.M. Holmes. Department of Ophthalmology, Mayo Clinic, Rochester, MN. Purpose: Binocular decorrelation in the first weeks of life produces the infantile esotropia syndrome in infant primates. The animals possess all of the behavioral features observed in strabismic children, including nasotemporal asymmetries of motion processing and gaze (latent nystagmus, pursuit, OKN and ocular following). The asymmetry is evident as a bias favoring nasalward motion. The goal of the present study was to determine which gaze and motion processing brain areas are more active for nasalward motion. Methods: A pilot functional imaging study was conducted in an anesthetized primate (age 2 yrs) who had infantile esotropia produced by 9 wks of prism goggle wear (binocular decorrelation). Anesthesia was accomplished with isoflurane (1-1.5%), and fMRI signals were recorded under conditions of dichoptic viewing using a surface coil. Blood-oxygenation level dependent (BOLD) images were obtained with 1.5 mm isotropic voxels and 2.25 mm of smoothing. Results: Eight trials of each of 4 conditions were tested, nasalward motion (2 conditions: right eye viewing leftward motion and left eye viewing rightward motion) vs. temporalward motion (2 conditions: right eye viewing rightward motion and left eye viewing leftward motion). A statistical map of the differential activation was derived and superimposed on a 3D reconstruction of the brain. Activation in the superior temporal sulcus in the vicinity of MT and MST was significantly stronger for nasalward compared to temporalward motion. The time course of the response was a sharp uptick in the first seconds with an overshoot followed by a long shallow downward ramp. Asymmetric activity (stronger for nasalward motion) was also apparent in VIP and FEF. Conclusions: These pilot data confirm that, in infantile esotropia, gaze-related regions of the cerebral hemispheres show asymmetries in activation for nasalward vs. temporalward visual motion. More data will be required to determine whether the locations of the activation-asymmetry differ with subtype of tracking behavior and to test hypotheses regarding other cortical and subcortical areas of interest (e.g. NOT). CR: W. Bentley, None; L. Snyder, None; S. Petersen, None; P. Foeller, None; L. Tychsen, None. Support: None Purpose: To investigate the effect of spectacles on the health related quality of life (HRQOL) of children and their parents using the new Intermittent Exotropia Questionnaire (IXTQ) and the PedsQL questionnaire. We were specifically interested in whether spectacle wear affected IXTQ scores. Methods: We recruited 41 children, median age 8 years (range 5 to 13), presenting with normal visual acuity (20/40 or better) and an otherwise normal eye examination (specifically no strabismus), who either had no refractive error (n=28) or had refractive error corrected with spectacles (n=13). One parent was recruited with each child. The IXTQ and PedsQL were completed, each comprised of a Child survey (self-report by child) and a Proxy survey (Child’s HRQOL from parent perspective). In addition, the IXTQ contains a Parent survey (self-report of the parent’s own HRQOL). Each questionnaire was scored from 0 (worst HRQOL) to 100 (best HRQOL). Median scores were calculated for each group (spectacles vs. no spectacles) and compared using Wilcoxon rank sum tests. Results: Child IXTQ scores were similar between both groups (92 with spectacles vs 90 without, P= 0.7) but Proxy IXTQ scores were lower for spectacle wearers (94 vs 100, P = 0.04). Proxy questions that scored lower in the spectacle group were related to teasing and feeling different. Parent IXTQ scores were lower for spectacle wearers (90 vs 97, P=0.002). Parent questions that scored lower in the spectacle group were related to parental worry about vision, surgery, self consciousness, and teasing. In contrast, for the PedsQL, composite scores and all subscale scores were similar between spectacle wearers and non-spectacle wearers, both for Child surveys (composite 82 vs 84, P>0.7 for all comparisons) and Proxy surveys (composite 96 vs 94, P>0.2 for all comparisons). Conclusions: HRQOL, as perceived by the parent, was lower for children wearing spectacles than that of children who did not wear spectacles using the Proxy IXTQ. Parental worry about their children wearing spectacles was also apparent using the Parent IXTQ questionnaire. Future uses of the IXTQ for intermittent exotropia need to account for spectacle wear. CR: T. Yamada, None; S.R. Hatt, None; D.A. Leske, None; J.M. Holmes, None. Support: NIH Grant EY015799 (JMH), Research to Prevent Blindness, Inc., and Mayo Foundation Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1983-1986 Monday, May 4, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 1979 - 1998 / D754 - D773 264. Strabismus II Organizing Section: EY 1987 - D762 Defining Real Change of Health Related Quality of Life Scores in Adults With Strabismus D.A. Leske, S.R. Hatt, J.M. Holmes. Department of Ophthalmology, Mayo Clinic, Rochester, MN. Purpose: Treatment for strabismus aims to improve function and health related quality of life (HRQOL), but real change in HRQOL scores has not been rigorously defined using test-retest data. The purpose of this study is to define real change in HRQOL scores in a cohort of strabismus patients using strabismus-specific and general vision-related HRQOL instruments. Methods: 12 adult patients with stable strabismus and no intervening treatment completed the NEI VFQ-25 and the new Adult Strabismus 20 (AS-20) HRQOL instruments. Questionnaires were completed a second time at a subsequent office visit. Test-retest differences were compared and 95% limits of agreement (LOA), a threshold value for real change, were calculated for composite scores and subscale scores. Results: As expected for a test-retest study, no statistically significant changes were seen in composite HRQOL scores or subscale scores for either the AS-20 or VFQ-25 (P = 0.08 to 1.0, signed rank). For the AS-20, the 95% LOA for the composite score was 17.3 points. The 95% LOA was 25.9 for the AS-20 functional subscale and 19.2 for the AS-20 psychosocial subscale. For the VFQ-25 composite score, the 95% LOA was 14.0. 95% LOAs for the VFQ-25 subscales ranged from 0 (no variability due to a ceiling effect) to 56.6 (large variability). Previous studies have identified peripheral vision and vision-specific social functioning, mental health, role difficulties, and dependency subscales as useful for diplopic patients but not non-diplopic patients. These subscales had 95% LOAs of 45.9, 21.2, 28.7, 24.7 and 12.1 respectively. Conclusions: A change of 17 points or more on the AS-20 is indicative of a real change of HRQOL in patients with strabismus. The VFQ-25 may be less useful for quantifying strabismus-specific HRQOL issues due to ceiling effects, large variability, and large LOA’s on several subscales. These data can now be used for responsiveness studies to further evaluate the usefulness of these instruments in assessing HRQOL of adults with strabismus. CR: D.A. Leske, None; S.R. Hatt, None; J.M. Holmes, None. Support: NIH Grant EY015799 (JMH), Research to Prevent Blindness, Inc., and Mayo Foundation 1989 - D764 Slow-Releasing All-Trans-Retinoic Acid in Polytetrafluoroethylene/PolylactideCo-Glycolide Laminate Delays Adjustment After Strabismus Surgery in Rabbit Model C. Kee1, J.-M. Hwang2, M. Lee3, T.-W. Kim 3, H.-K. Choungv3. 1Ophthalmology, Samsung Medical Center, SKK Univ., Seoul, Republic of Korea; 2Ophthalmology, Seoul National University College of Medicine, Seongnam, Republic of Korea; 3 Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea. Purpose: To determine the usefulness of slow-releasing all-trans-retinoic acid (ATRA) in polytetrafluoroethylene/polylactide-co-glycolide (PTFE/PLGA) laminate for delayed adjustable strabismus surgery. Methods: A prospective, masked-observer, controlled study was performed in 25 rabbits. Fifty rabbit eyes were divided randomly into three groups. After a recession of the superior rectus muscle (SRM), a PTFE/PLGA laminate containing ATRA, PTFE alone, or balanced salt solution was applied beneath and over the SRM in the PTFE/ PLGA-ATRA group (group ATRA), the PTFE group (group PTFE) and the control group, respectively. Results: At 5 weeks postoperatively, group PTFE and group ATRA showed better adjustability than the control group. In addition, there was less adhesion in group PTFE or group ATRA than the control group in terms of adhesion between SRMs and conjunctivae at 5 weeks postoperatively. Only group ATRA showed less adhesion than the control group in terms of adhesion between SRMs and sclerae at 5 weeks postoperatively. Conclusions: Slow-releasing ATRA in PTFE/PLGA was found to reduce adhesion and allowed delayed adjustment in most eyes for up to five weeks postoperatively. CR: C. Kee, None; J.-M. Hwang, None; M. Lee, None; T.-W. Kim, None; H.-K. Choungv, None. Support: a grant of the Korea Health 21 R&D Project, Ministry of health, welfare and family affairs, Republic of Korea (A080299) 1988 - D763 Saccade Abnormality in Idiopathic Intracranial Hypertension Y.-R. Chen, Y.J. Liao. Ophthalmology, Stanford University, Stanford, CA. Purpose: To characterize the horizontal saccade abnormality and to assess the effectiveness of acetazolamide in patients with idiopathic intracranial hypertension (IIH). Methods: We recruited 13 consecutive patients with IIH regardless of symptoms of presentation for clinical assessment and eye movement recording at an academic institution over one year. Six patients had paired recordings that allowed intra-subject comparison of the efficacy of acetazolamide treatment. Binocular infrared oculography at 500 Hz was performed before and during acetazolamide treatment. Randomized, repetitive visual stimuli were presented with custom program written in Presentation. Data was analyzed with custom-written programs in MATLAB and IgorPro. Results: While most patients had no symptomatic binocular diplopia at presentation, those with clinically evident abduction abnormality exhibited small esophoria in primary gaze, which worsened at left or right gaze. Reflexive horizontal saccades showed bilateral or unilateral abduction deficits in the majority of patients with IIH. This was evident during the plateau phase of the saccade as well as in the initial dynamic overshoot. In 6 patients with paired recording, 83% had abduction deficits. The difference between the abducting and adducting eyes in 12 degree rightward saccades was 0.984 ± 0.202 deg, and for 12 degree leftward saccades, 0.809 ± 0.159 deg. Treatment with acetazolamide (1000-2000 mg per day) led to the rapid resolution of abduction deficit and ocular misalignment, with the average plateau difference of rightward saccade improving by 86% (0.134 ± 0.153 deg, n = 6, P = 0.0016), and the leftward saccade improving by 67% (0.267 ± 0.154 deg, n = 6, P = 0.0175). The amelioration of ocular mismatch during reflexive saccades occurred early, well before the resolution of papilledema. Conclusions: Abduction deficit, most likely a result of cranial nerve VI dysfunction due to elevated intracranial pressure, occurred in more than 50% of patients with IIH, even in the absence of subjective binocular diplopia. This abnormality quickly resolved following acetazolamide treatment. Our study highlighted the utility of eye movement recording in assisting the diagnosis and monitoring of patients with IIH. CR: Y.-R. Chen, None; Y.J. Liao, None. Support: Career Award in Biomedical Sciences from the Burroughs Wellcome Foundation, NIH Grant K08 NS044268, Stanford Medical Scholars Program. 1990 - D765 Vertical Vergence Adaptation Produces an Incomitant Transient Cyclovertical Deviation Changing With Gaze Direction and Head Tilt H.S. Ying1A, K. Irsch1B, N.A. Ramey1B, D.L. Guyton1B. ARetina, BPediatric Ophthalmology and Strabismus, 1Johns Hopkins Wilmer Eye Institute, Baltimore, MD. Purpose: With the aim of understanding the cyclovertical mechanisms involved in both binocular fusion and ocular misalignment, we asked normal volunteers to adapt to a steadily increasing vertical misalignment. Methods: We designed and built a novel research haploscope capable of tilting with the subject 45 degrees to the right or the left about the naso-occipital axis and measuring binocular horizontal, vertical, and torsional eye movements with video oculography. Circular targets consisting of multicolored concentric circles without torsional cues and subtending >54 degrees were used to stimulate vertical vergence. Two subjects with normal orthoptic exams were instructed to fuse a gradually increasing right over left target disparity in straight head position for 30 minutes. Static eye positions were measured during monocular viewing in the nine diagnostic positions of gaze (10-degree excursions) with head straight and tilted 45 degrees right and left. Subjects re-fused right over left target disparity between measurements in different head tilts. Results: After adaptation, both subjects developed a transient cyclovertical ocular deviation with at least two degrees of vertical deviation in the straight ahead position. The right hyperdeviation decayed slowly over 60 to 90 seconds. This hyperdeviation increased in down gaze or with 45-degree left tilt and reduced with 45-degree right head tilt. Relative extorsion that was greatest in left gaze developed in all three head tilts. An esodeviation also developed in most positions of gaze which increased with tilt to either side. Conclusions: Changes in a vertical deviation with head tilt are often taken as evidence for a cyclovertical muscle paresis. These results indicate that vergence adaptation may induce a transient cyclovertical deviation that can also show changes with head tilting. Therefore, changes in vertical deviation with head tilting are not pathognomonic of cyclovertical muscle paresis. CR: H.S. Ying, None; K. Irsch, None; N.A. Ramey, None; D.L. Guyton, None. Support: NIH Grant EY19347, NIH Grant EY15025, Knights’ Templar Eye Foundation Young Investigator Award, Research to Prevent Blindness Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1987-1990 Monday, May 4, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 1979 - 1998 / D754 - D773 264. Strabismus II Organizing Section: EY 1991 - D766 Influence of Physiologic Diplopia Suppression on Phoria Maintenance in Inttermittent Exotropia 1992 - D767 Surgical Correction of Childhood Intermittent Exotropia Does Not Influence the Development of Mental Illness A. Wakayama, K. Ohmure, F. Matsumoto, K. Abe, Y. Shimomura. Ophthalmology, Kinki Univ Sch of Medicine, Osaka-Sayama, Japan. R.A. Barraza1A, J.A. McKenzie1B, N.N. Diehl2, B.G. Mohney3. AMayo Medical Scientist Training Program, BCollege of Medicine, 1Mayo Clinic College of Medicine, Rochester, MN; 2Division of Biostatistics, Mayo Clinic College of Medicine and Mayo Foundation, Jacksonville, FL; 3Department of Ophthalmology, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN. Purpose: Because control of phoria is important for managing intermittent exotropia, we investigated how the maintenance of phoria could be affected by suppression of physiological diploia. Methods: Subjects were 50 patients with intermittent exotropia, who were under 15 years old (mean age, 9.0±2.3 years) and could be examined for suppression of physiologic diplopia. Thirty-four of the 50 patients had received one operation, orthoptic training, or both previously; and 23 of the 34 patients could maintain phoria after treatment. Deviations at near and far distances were 20.3±9.3PD and 18.0±8.7PD, respectively. Presence of suppression was assessed under phoria condition by physiologic diplopia test and when convergence broke. Relationships between phoria maintenance and suppression, non-dominant eye and deviating eye when convergence broke, and dominant eye and dominant hand were all investigated. Results: Twenty-two (44.0%) of the 50 patients showed suppression of physiological diplopia under phoria condition, and 18 (81.1%) of the 22 patients also indicated suppression when convergence broke. A significant correlation was seen between suppression under phoria condition and when convergence broke (p<0.001). Twentythree (46%) of the 50 patients indicated phoria maintenance and only 2 (8.7%) of them showed suppression under both conditions. This indicated that patients capable of phoria maintenance did not suppress under phoria condition and when convergence broke. In those 27 patients not capable of phoria maintenance, 16 (59.3%) were seen with suppression under both conditions. This suggested that patients not capable of phoria maintenance suppressed under phoria condition and when convergence broke. A significant correlation was seen between the presence of suppression and the maintenance of phoria (p<0.001). Deviating eye when convergence broke and nondominant eye corresponded in 87.1% of the 50 patients. Dominant eye and dominant hand corresponded in 68.0%. Conclusions: Under phoria condition, patients who can maintain phoria condition did not suppress. This shows the association between the presence of suppression and maintenance of phoria. CR: A. Wakayama, None; K. Ohmure, None; F. Matsumoto, None; K. Abe, None; Y. Shimomura, None. Support: None Purpose: We recently demonstrated that children with intermittent exotropia, compared to age- and gender-matched controls, are at an increased risk for developing mental illness by early adulthood. The purpose of this study was to assess whether surgical intervention, or the timing of intervention, had any effect on the prevalence of mental illness. Methods: The medical records of all children (<19 years) diagnosed with intermittent exotropia (n = 183) as residents of Olmsted Country, Minnesota, between January 1, 1975, and December 31, 1994, were retrospectively reviewed for parameters concerning treatment and the development of mental illness. Results: Ninety-seven (53.3%) of the 183 children were diagnosed with a mental illness when followed to a mean age of 23.3 years (range, 6 to 41 years). Thirty three (34%) of the 97 children who developed mental illness underwent surgery while the remaining 64 did not have surgery (p=0.75). Neither age at surgery (< 10 years of age) (p=0.98) nor success at surgery (< 10 prism diopters) (p=0.66) were associated with a decreased occurrence of mental illness by early adulthood. Additionally, of the 86 patients who did not develop mental illness, strabismus surgery, when it occurred, was not more common (p=0.71) or at a younger age (p=0.15) when compared to the 97 patients who later developed mental illness. Conclusions: Strabismus surgery, regardless of success or age at surgery, for children with intermittent exotropia did not decrease or otherwise alter the development of mental illness by early adulthood. CR: R.A. Barraza, None; J.A. McKenzie, None; N.N. Diehl, None; B.G. Mohney, None. Support: Research to Prevent Blindness 1993 - D768 Detection of Socially Significant Strabismus by Lay Observers in a Culturally Diverse Model Set 1994 - D769 Does Strabismus Surgery Improve Functional Outcomes in Children With Cerebral Palsy? Gross Motor Function Classification Scale K.W. Chan1,2A, E.M. Weissberg2A, L. Deng2B. 1Pediatric Ophthalmology and Strabismus, Massachusetts Eye and Ear Infirmary, Boston, MA; ASpecialty and Advanced Care, BVision Science, 2New England College of Optometry, Boston, MA. F.F. Ghasia1A, J. Brunstrom1B, L. Tychsen1C. ADept of Ophthal and Visual Sciences, B Dept of Neurology, Dept of Pediatrics, CDept of Ophthal and Visual Sciences, Dept of Pediatrics, 1Washington University St Louis, St. Louis, MO. Purpose: Patients with socially significant strabismus may suffer both visual and psychosocial consequences. The magnitude at which strabismus becomes socially significant is unclear. Previous publications have suggested exotropia (XT) is easier to detect than esotropia (ET), with critical magnitude of detection (>70% detection) described at approximately 8Δ for XT and 14.5Δ for ET. However, both these studies used only one, female, Caucasian model. This study will further examine the critical magnitude of detectable strabismus by lay observers in a more culturally diverse model set. Methods: Twelve models of variable ethnicity (4 African American (AA), 4 Asian (AS) and 4 Caucasian (CA)) with equal number of female and male models within each race were digitally photographed in a range of horizontal gaze positions. Strabismus ranging from ET 21Δ to XT 21Δ was simulated using photo manipulation. Images were presented in a randomized order to 102 non-health care professional observers who were asked to decide whether strabismus was present or not. The magnitude of strabismus with a 70% positive response rate was defined as the critical magnitude. Results: Overall, an increase in likelihood of strabismus detection was noted as the angle of strabismus increased. For all models combined, critical magnitude for detecting ET was 18.82Δ (95% C.I. (18.34Δ, 20.38Δ)) and XT was 16.63Δ (95% C.I. (15.46Δ, 17.26Δ)), indicating XT was slightly easier to detect than ET. Differences were noted among race. The critical magnitude for detecting ET for AS models was 14.25Δ (12.91, 15.60) compared to 20.88Δ (18.54, 25.32) for XT. AA and CA data showed an opposite trend with critical magnitude being 20.82Δ (19.26, 22.37) for ET and 16.29Δ (15.52, 17.25) for XT in AA models and 23.17Δ (20.43, 27.43) for ET and 13.53Δ (12.70, 14.64) for XT in CA models. The positive response rate at ortho position (false positive rate) was lowest for AA followed by CA with a higher response rate for AS models. Large variability in critical magnitude of detection was found among the 12 models implying no uniform detection angle may exist across individuals. Conclusions: XT was slightly easier to detect than ET for all models combined. Race differences were observed with ET being easier to detect than XT in AS models and the opposite trend in AA and CA models. Large inter-model variability may suggest difficulty generalizing results of this and similar studies and raises the question whether guidelines for socially significant strabismus can be applied to an entire population. CR: K.W. Chan, None; E.M. Weissberg, None; L. Deng, None. Support: NEI Grant R24 EY014817 Purpose: To determine binocular sensory and motor outcomes after strabismus surgery in children with cerebral palsy (CP). Methods: A cross-sectional observational study was conducted on 50 children whose CP severity spanned milder (level 1-2) to severe (level 3-5) using the standardized Gross Motor Function Classification System. Optimal motor outcome was defined as 8 PD or less deviation (microtropia) 1 yr post-surgery; sensory outcome was defined as restoration of fusion or stereopsis. Mean age = 3.5 yrs; mean follow-up = 4.1 yrs. Across GMFCS levels children did not differ in gestational age, examination age, preoperative angle or follow-up period (ANOVA p=0.9, p=0.23, p=0.53 respectively). Results: Children with mild CP achieved a 2.6x greater rate of optimal motor outcome and 3.1x greater stereopsis outcome compared to children with severe CP (50% vs. 19% and 25% vs. 8%). Gain of binocularity was 1.7x greater in children with primary ET (63%) versus primary XT (37%). Outcomes did not differ in children with stable vs. variable-angle preoperative deviation (chi sqr p=0.5). In primary ET children, 38% had optimal motor outcome after 1 surgery and 71% after 2 surgeries. 42% of primary ET children developed a secondary macro XT after 1 surgery, which responded favorably to a 2nd surgery. Shorter duration of strabismus before surgery 1 was associated with better motor outcome [2.6 yrs vs. 4.3 yrs in suboptimal-macrotropia outcome (p=0.05)] and gain in binocularity [2.1 yrs vs. 4.8 yrs (p=0.05)]. Children with dyskinetic strabismus (variable ET/XT) did not achieve optimal motor outcome or gain in binocularity. Conclusions: Children with milder CP, primary ET and earlier treatment benefit substantially from strabismus surgery. Variable deviation and secondary XT is common, but should not deter earlier treatment. CR: F.F. Ghasia, None; J. Brunstrom, None; L. Tychsen, None. Support: 5-T32-EY13360-05 ,1 F32 EY016964-01A1 ,Gustavus and Louise Pfeiffer foundation,Walt and Lilly Disney Scholars Award for Amblyopia Research Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1991-1994 Monday, May 4, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 1979 - 1998 / D754 - D773 264. Strabismus II Organizing Section: EY 1995 - D770 Long Term Outcomes, in Different Degrees of Compliance With Wearing Spectacles, in Children With Accommodative Esotropia 1996 - D771 Appearance of V Pattern Strabismus and Inferior Oblique Overaction After Sixth Nerve Palsy in Children M.A. Hussein, D.R. Weakley. Ophthalmology, UTsouthwestern medical center, Dallas, TX. S.M. Culican, S. Khanna. Ophthal & Vis Sciences, Washington University, Saint Louis, MO. Purpose: The aim of this study is to evaluate, retrospectively, the long term outcome of children with accommodative esotropia, who are not compliant with wearing their spectacles. Methods: We reviewed the charts of patients who had a diagnosis of accommodative esotropia , had at least 3 diopters of hyperopia , and who had at least one year of follow up. We divided patients according to the degree of compliance with wearing spectacles into good , fair , and poor compliance.The main outcome measures for treatment were the sensory and motor outcomes. Results: Ninety two patients met our inclusion criteria. The mean follow up was 61.4 months (from 12 to 200 months).When comparing patients with good compliance to those with fair compliance, fair compliance was associated with significant higher risk for poor sensory outcome (Odd Ratio 4.5507, 95% CI from 2.1 to 24.7, P value = 0.0003 ), and poor motor outcome (Odd Ratio, 4.11, 95% CI from 1.44 to 11.75, P value = 0.0065). When comparing patients with good compliance to those with poor compliance, poor compliance was associated with higher risk for poor sensory outcome (Odd Ratio, 12.3236, 95% CI from 1.29 to 96.79, P value = 0.0061) and motor outcome(Odd Ratio, 11.6644, 95% CI from 2.38 to 74.19, P value = 0.0006 ) Conclusions: Our results underscore the importance of finding alternative ways for managing non-compliant children with accommodative esotropia. CR: M.A. Hussein, None; D.R. Weakley, None. Support: None Purpose: To study the occurrence of primary inferior oblique overaction and V pattern strabismus with acquired sixth nerve palsy in children. Methods: Retrospective chart review of ophthalmologic/ orthoptic examination of patients with isolated sixth nerve palsy seen in the children’s Eye Clinic over the last 5 years. 5 patients met the criteria for isolated sixth nerve palsy. Results: Two of the five patients had bilateral sixth nerve palsies that resolved completely with no residual esotropia (ET). These patients did not manifest any inferior oblique overaction (IOOA) at any time. Three patients manifested residual ET at the 2-3 months follow-up visit and manifested inferior oblique overaction. Two of these three patients had unilateral palsy with onset of IOOA on the ipsilateral side of the sixth nerve palsy. One patient with bilateral sixth nerve palsy developed IOOA bilaterally. Conclusions: Children who suffer sixth nerve palsy and have residual esotropia develop the ocular motor signs of primary inferior oblique overaction. We speculate that in these children there is residual orbital layer weakness of the lateral rectus which displaces the lateral rectus pulley, thereby altering the dynamics of inferior oblique action and manifesting as IOOA. CR: S.M. Culican, None; S. Khanna, None. Support: NEI- K12 EY016336 1997 - D772 Effectiveness of Placebo Therapy for Maintaining Masking in a Clinical Trial of Vergence/Accommodative Therapy 1998 - D773 Improvement in Academic Behavior Following Successful Treatment of Convergence Insufficiency M.T. Kulp1, G.L. Mitchell1, E. Borsting2, M. Scheiman 3, S. Cotter2, M. Rouse2, S. Tamkins 4, B.G. Mohney5, A. Toole1, CITT Study Group. 1College of Optometry, Ohio State University, Columbus, OH; 2College of Optometry, Southern California, Fullerton, CA; 3Pennsylvania College of Optometry, Salus University, Philadelphia, PA; 4 Bascom Palmer Eye Institute, Miami, FL; 5Mayo Clinic, Rochester, MN. E. Borsting1, M.W. Rouse1, L. Mitchell2, M.T. Kulp2, M. Scheiman 3, S. Cotter1, CITT Study Group. 1Clinical Science, Southern California Coll of Optometry, Fullerton, CA; 2College of Optometry, Ohio State University, Columbus, OH; 3Pennsylvania College of Optometry, Salus University, Philadelphia, PA. Purpose: To determine if demographic variables affected masking of subjects in the Convergence Insufficiency Treatment Trial (CITT) and whether perception of assigned treatment group was associated with treatment outcome or adherence to treatment. We also evaluated the effectiveness of the CITT placebo therapy program in maintaining masking of patients randomized to the office-based treatment arms. Methods: Patients (n=221, ages 9 to 17 years) were randomized to one of 4 treatment groups; 2 of which were office-based and masked to treatment (n=114). The placebo therapy program was designed to appear like real vergence/accommodative therapy, without stimulating vergence, accommodation, or fine saccades (beyond levels of daily visual activities). After treatment, patients in the office-based groups were asked if they thought they received real or placebo therapy and how confident they were in their answer. Results: Ninety-three percent of patients assigned to real therapy and 85% assigned to placebo therapy thought they were in the real therapy group (p=0.17). No significant differences were found between the two groups in adherence (p≥0.22 for all comparisons). The percentage of patients who thought they were assigned to real therapy did not differ by age, gender, race or ethnicity (p > 0.30 for all comparisons). No association was found between patients’ perception of group assignment and symptoms or signs at outcome (p≥0.38 for all comparisons). Conclusions: The CITT placebo therapy program was effective in maintaining patient masking in this study and, therefore, may potentially be used in future clinical trials using vergence/accommodative therapy. Masking was not affected by demographic variables. Perception of group assignment was not related to symptoms or signs at outcome. CR: M.T. Kulp, None; G.L. Mitchell, None; E. Borsting, None; M. Scheiman, None; S. Cotter, None; M. Rouse, None; S. Tamkins, None; B.G. Mohney, None; A. Toole, None. Support: U10EY014713, U10EY014659, U10EY014716, U10EY014715, U10EY014709, U10EY014710, U10EY014676, U10EY014706, and U10EY014712 from the National Eye Institute CT: www.clinicaltrials.gov, NCT00338611 Purpose: To determine whether successful treatment of Convergence Insufficiency (CI) has an impact on parents’ perceptions of the frequency of problem behaviors that their child may exhibit when reading or performing school work (such as: difficulty completing work, avoidance, and inattention) and parental concern about academic performance as measured by the Academic Behavior Survey (ABS). Methods: The ABS was administered at baseline and after 12 weeks of treatment to the parents of 218 children ages 9-17 years with symptomatic CI, who were enrolled in the Convergence Insufficiency Treatment Trial and randomized into one of four treatment groups. The ABS is a 6-item survey that quantifies the frequency of observed behaviors and parental concern on an ordinal scale from 0 (never) to 4 (always) with a total score ranging from 0 to 24. Participants were classified as successful (n=42), improved (n=60), or non-responder (n=116) at the completion of 12 weeks of treatment using a composite measure of the CI Symptom Survey, near point of convergence, and positive fusional vergence. Analysis of covariance methods were used to compare the mean change in ABS between the groups while controlling for the ABS score at baseline. Results: The mean ABS score for the entire group at baseline was 12.85 (SD=6.3). The mean ABS score decreased in those categorized as successful, improved, and nonresponder by 4.0, 2.9, and 1.3 points respectively. The improvement in the ABS score was significantly related to treatment outcome (p<0.0001). Conclusions: Improvements in the signs and symptoms of CI after treatment were associated with a reduction in the frequency of problem behaviors associated with reading and school work as reported by parents on the ABS. CR: E. Borsting, None; M.W. Rouse, None; L. Mitchell, None; M.T. Kulp, None; M. Scheiman, None; S. Cotter, None. Support: Supported by NEI/NIH, DHHS U10 grants: EY014713, EY014659, EY014716, EY014715, EY014709, EY014710, EY014676, EY014706, EY014712 CT: www.clinicaltrials. gov, NCT00347945 Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 1995-1998 Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2827 - 2840 / A82 - A95 323. Nystagmus Organizing Section: EY 2827 - A82 Normative Data on Maximum Angle of Abduction and Nystagmus Onset Angle R.M. Williams1, S.B. Stevenson1, J.M. Wensveen1, S.J. Rubenzer2. 1College of Optometry, University of Houston, Houston, TX; 2Private Practice, Houston, TX. Purpose: Horizontal Gaze Nystagmus is assessed by law enforcement as one part of the Standardized Field Sobriety Test, where nystagmus that occurs at gaze angles less than 45 degrees increases suspicion of intoxication, though little normative data have been reported on gaze evoked nystagmus, or on the role of factors such as fatigue. We measured the maximum angle of abduction and the angle of onset of nystagmus in 103 sober individuals, and looked for fatigue effects in 4 subjects. Methods: Subjects were seated with head stabilized and positioned so that the left eye was directly over the pivot of a rotating arm carrying a camera, infrared LED source, and a small mirror. The camera provided experimenters with a magnified view of the eye that stayed on axis with gaze direction as the arm rotated. The arm was moved in 5 degree increments, and gaze stability and accuracy were assessed at each position. Nystagmus onset was recorded as the smallest angle at which distinct nystagmus of at least 3 beats was noted. Maximum deviation was recorded as the largest angle for which the target remained centered in the pupil image. For the large sample, measurements were made on optometry students during a morning laboratory exercise. For the fatigue study, repeated measures were made on both eyes of 4 subjects at 3 different times of day spanning a 12 hour period. Measurements were repeated on 5 days. Results: The maximum angle of abduction varied from 35 to 65 degrees, with mean of 48 +/- 5.9 degrees. Nystagmus occurred in 70/103 subjects, with a mean angle of onset 44 +/- 6.0 degrees. For 28/103 subjects the angle of onset was the same as the maximum deviation. The fatigue study showed that both measures increased slightly with time of day but the effect was not significant (repeated measures ANOVA, df 3, 2, F 1.952, p 0.2449). Conclusions: End gaze nystagmus is a common finding in the general population, suggesting that the roadside HGN test may suffer from a high false positive rate. 70 of 103 subjects showed nystagmus at max deviation, and half of our sample showed nystagmus at or before 45 degrees. Fatigue did not have a significant effect on the occurrence or magnitude of nystagmus in our sample. CR: R.M. Williams, None; S.B. Stevenson, None; J.M. Wensveen, None; S.J. Rubenzer, None. Support: NIH grant T35 EY07088-18 2828 - A83 Increasing Salience of the Moving Stimulus Impairs OKN Suppression More Than Does Spreading Spatial Attention L.A. Abel1, H.N. Nguyen1, C.J. Lueck 2, I.M. Williams3. 1Optometry & Vision Sciences, University of Melbourne, Carlton, Australia; 2Neurology, Canberra Hospital, Canberra, Australia; 3Medicine, Monash University, Melbourne, Australia. Purpose: Although a full-field high contrast stimulus rotating around a subject elicits a strong response of optokinetic nystagmus (OKN), normal individuals can suppress this nearly completely by actively fixating a stationary point in the otherwise moving environment. This requirement for active fixation raised the possibility that if attention were simultaneously directed elsewhere in the visual field, then OKN suppression might be impaired. In a recent study (Williams et al, 2006) we demonstrated that if subjects were required to detect the first appearance of a feature of the OKN stimulus (a red T in a row of red Cs and blue Ts), that OKN suppression declined in an age-dependent manner. It was unclear, however, whether this was due to directing attention towards the OKN stimulus or to having to spread it over a wide spatial area. The present study addresses this question. Methods: 15 healthy subjects aged sat in the centre of a full-field stimulus 1.5 m in diameter moving at 24°/s and composed of columns of red Cs and blue Ts, with the eye-level row also containing 3 red Ts. Red laser spots were projected on the curtain under computer control at 0° and 7.5° left or right. After baseline “stare” OKN testing, all other tasks required subjects to fixate a 0° spot. 3 tasks required detection of a blink of either the central or peripheral laser spot and 3 required detection of a red T passing the same spots. OKN gain was measured for all tasks and compared with Friedman’s ANOVA and also regressed against subjects’ ages. Results : Mean gains on the 3 blink detection tasks were 0.06, 0.05 and 0.06; on the corresponding T detection tasks they were 0.14, 0.15 and 0.16. ANOVA showed a significant main effect of task on gain (p<.001); pairwise post-hoc tests found significant gain differences (p<.05) when detecting blinks vs. detecting red Ts. Regressions against age were all non-significant. Conclusions: For the 6 detection tasks, stimulus conditions were identical across the pairs of tasks but attention was directed either towards the moving curtain or the static laser spot at each location. Gain was significantly higher when the OKN stimulus was made more salient via top-down allocation of attention. The lack of an age effect may result from 7.5° targets not sufficiently stretching the attentional spotlight to stress even elderly subjects’ resources. CR: L.A. Abel, None; H.N. Nguyen, None; C.J. Lueck, None; I.M. Williams, None. Support: None 2829 - A84 The Clinical Spectrum of Involuntary Horizontal “End-on-End” Saccades 2830 - A85 Hyper Acuity Target Improve Fixation Stability M.L. Rosenberg. Neurology, New Jersey Neuroscience Institute, Edison, NJ. T. Pansell1, S. Giovagnoli2, R. Bolzani2, B. Zhang1, J. Ygge1. 1Ophthalmology Department, Karolinska Institutet, Stockholm, Sweden; 2Psychology Department, Bologna University, Bologna, Italy. Purpose: Voluntary nystagmus is a well known entity most commonly encountered in the setting of a patient seeking secondary gain. At times however voluntary nystagmus can be indistinguishable from ocular flutter either by clinical exam or by eye movement recordings. The situation can be made more complex as there are patients reported who admit to spells of voluntary nystagmus but also note episodes that are said not to be under their control. To try and better understand this condition patients with end on end saccades from any condition were collected retrospectively from cases seen by the author. Methods: Patient records available for computer searching were evaluated for cases noted on clinical examination to have end on end saccades. Other clinical findings, the final diagnosis and radiological findings were gathered from the clinical and the hospital records. Patients who admitted to voluntary nystagmus or who had evidence of secondary gain or other psychological difficulties were excluded. Patients with micro-flutter were also not included in this study. 66 patients were included in this study. Results: Of the 66 patients 13 were found to have involuntary flutter-like movements on exam but were diagnosed as being normal. 48 were found to have a specific neurological disagnosis while 5 had neurological problems of unclear etiology. The most common diagnosis was multiple sclerosis. The abnormal saccades were noted at times to be induced by convergence (26), saccades (6), or pursuit movements (6), while at other times were spontaneous (46). Conclusions: Not all patients with what appears to be ocular flutter have an underlying neurological problem, although most do. Similarly not all those with what appears to be voluntary nystagmus are free of underlying neurological disease. All patients with spontaneous flutter or flutter induced by pursuits or saccades, who did not have similar movements inducible by convergence, had neurological disease. All subjects with flutter-like movements induced by saccades were also found to have underlying neurological disease. Ocular flutter, with or without an association with convergence, was rarely the only sign on initial exam of neurological disease. Although clinically difficult at times, it is critically important to distinguish voluntary nystagmus from ocular flutter. Although psychological disorders are not always clinically obvious, the absence of a clear secondary gain should be an important clue to look for a possible organic process. CR: M.L. Rosenberg, None. Support: None Purpose: A slow oscillation of eye position (±0.5 deg, 0.1 Hz) was recently described when analyzing fixational eye movements by means of a Fourier transformation (poster Zhang et al., ARVO 2009). The underlying purpose of this eye movement is not known. This study investigated the influence of hyper acuity targets on this ocular oscillation. Many studies have reported that the visual hyperacuity, the ability to perceive visual information presented under the threshold of visual acuity is mainly related to the magnocellular system, which is supposed to be of advantage for visual stabilization. Our hypothesis is that the fixation of a hyper-acuity target is more stable than the fixation of a super threshold target. Methods: Eye movements were recorded binocularly (VOG, Chronos Vision; 100 Hz) in seven healthy subjects during a fixation task. Three targets were used in a randomized procedure for each subject in three tests (180 sec). i) hyper-acuity target (dot obtained by a number of concentric circles with distances between each other under the visual acuity threshold) ii) visible target (dot made by concentric circles with distances each other over the visual acuity threshold), and iii) solid target (control target, a grey dot). All the targets had the same luminosity (23 cd/m²), size (visual angle 0.9 deg) and were presented at the same eye-screen distance (50 cm). The subjects were instructed to fixate the target. Results: Significant differences were found in the characteristics of the oscillation between the targets (F=2.49; p< .05). The oscillation was faster and the amplitude was smaller in response to the hyper acuity target compared to the other two targets. The faster oscillation might be caused by a constant eye velocity in a narrower fixation area. Conclusions: These results suggest that the oscillation of fixational eye movements is more stable when fixating a hyper acuity target. Fixation is more stable when only the magnocellular system is stimulated compared to when both the parvocellular and mangocellular systems are involved. CR: T. Pansell, None; S. Giovagnoli, None; R. Bolzani, None; B. Zhang, None; J. Ygge, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 2827-2830 Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2827 - 2840 / A82 - A95 323. Nystagmus Organizing Section: EY 2831 - A86 Torsional Optokinetic Nystagmus in Strabismus 2832 - A87 Survey of Diagnosis of Nystagmus in the United Kingdom S.J. Farooq, R.J. Mclean, F.A. Proudlock, I. Gottlob. Ophthalmology, University of Leicester, Leicester, United Kingdom. I. Choudhuri1, N. Sarvananthan1, I. Gottlob2. 1Ophthalmology, Leicester Royal Infirmary, Leicester, United Kingdom; 2Ophthalmology, University of Leicester, Leicester, United Kingdom. Purpose: Torsional optokinetic Nystagmus (tOKN) in patients with strabismus since childhood has not been previously evaluated. The authors investigated the optokinetic response in horizontal, vertical and torsional directions in strabismus patients and in age-matched normal volunteers. Methods: Monocular torsional, horizontal and vertical eye movements were recorded in 16 subjects with childhood strabismus and 15 normal volunteers. Constant velocity horizontal (nasalward and temporalward) and vertical (upward and downward) OKN stimuli were used at 10°/s, 20°/s and 40°/s. Torsional (intorsion and extorsion) OKN stimuli were rotated at velocities of 40° and 400°/s. Results: OKN responses from strabismus patients produced significant asymmetric responses in horizontal and vertical meridians. The nasalward response was significantly greater than the temporalward (p=3.64x10 -6 for the non-dominant eyes, p=7.18x10 -9 for the dominant eyes) and upward response was greater than downward (p=0.0029 for the non-dominant eyes, p= 0.0043 for the dominant eyes. A significant high incidence of absent tOKN was present at both stimulus velocities in the intorsion direction (p= 0.024 for 40°/s, p=0.0085 for 400°/s) and at 400°/s in the extorsion direction (p= 0.040). Eight of the 15 patients tested did not respond to any stimulus in either direction in their non-dominant eye and 4 showed no response in their dominant eye. Conclusions: Torsional OKN is dramatically affected in the presence of strabismus with a high incidence of no response. The possibility of a lack of development in the binocular cortical structures that respond to torsional motion could explain these findings. CR: S.J. Farooq, None; R.J. Mclean, None; F.A. Proudlock, None; I. Gottlob, None. Support: None Purpose: Nystagmus causes significant symptoms of visual reduction with or without oscillopsia in many individuals. There is no consensus regarding the best way to investigate these patients. Methods: A questionnaire was sent to all ophthalmologists in the United Kingdom. Information about sub-speciality interest, examinations/investigations done for nystagmus patients, and investigations they would like to be available for nystagmus patients were collected. Results: Out of 893 questionnaires sent, 411were returned Twenty one responses were from neuro-ophthamologists, 108 were from paediatricophthalmologists, 12 declared overlapping neuro/paediatric interests, while the remaining were from other ophthalmic specialities. The examinations currently done by ophthalmologists as routine were, orthoptic examinations (n=304), electrophysiologic tests (n=204), blood tests (n=39), imaging (n=211), genetic testing (n=132) and visual fields (n=127). Forty five have been performing eye movement recording as referrals. Ninety one do not see nystagmus patients. Three hundred and seven ophthalmologists wanted orthoptic facilities to be available, 250 wanted electrophysiology, 82 wanted blood tests, 232 imaging, 188 genetics, 148 visual field. 174 ophthalmologists felt eye movement recordings would be helpful in the managment of nystagmus Conclusions: Most ophthalmologists are seeing nystagmus patients. There is a demand to increase access of eye movement recordings and genetic testing. CR: I. Choudhuri, None; N. Sarvananthan, None; I. Gottlob, None. Support: None 2833 - A88 Voluntary Modulation of Involuntary Eye Movements During Reading 2834 - A89 A Study Assessing the Effect of Tenotomy Procedures on Infantile Nystagmus M.G. Thomas, F.A. Proudlock, R.J. McLean, I. Gottlob. Ophthalmology Group, University of Leicester, Leicester, United Kingdom. R.J. McLean, A. Kumar, F.A. Proudlock, I. Gottlob. Ophthalmology Group, University of Leicester, Leicester, United Kingdom. Purpose: To understand how individuals with infantile nystagmus read in view of the sensory motor deficits associated with this condition. Methods: Eye movement recordings were carried out in healthy (n=7), IIN (n=14) and albino (n=10) volunteers during reading for distance (1.2m) and near (0.33m) at five gaze positions (-20°, -10°, 0°, 10° and 20°). Reading speeds (RS) and beating pattern were derived from these recordings. Visual acuity (VA) was also measured over the same eccentricities and distances. The nystagmus volunteers underwent a further fixational task over the same eccentricities to derive the waveform characteristics of nystagmus. Results: RS were significantly (p<0.05) slower in nystagmus volunteers when compared to age and IQ matched controls. VA is a good predictor of RS in IIN (R 2 = 0.48, p<0.05) but not albinism (R 2 = 0.08, p<0.05). Right beating waveform was associated with faster RS and left beating with slower RS (p<0.05). Intensity had a significant effect on RS in IIN (p<0.05); however, it was a poor predictor of RS (R 2 = 0.12). There was a change in the nystagmus waveform when fixating a target and when reading. During reading around the null point most volunteers used a pendular waveform which was modulated by the quick phases while during fixation different waveforms were encountered. The voluntary modulation of the nystagmus is further substantiated by the difference in frequency between the fixational task and the reading task. Conclusion: We describe, for the first time, that VA is a reliable measure of RS in IIN but not in albinism. However, intensity does not predict RS. Therefore oculomotor recordings and VA measurements should be supplemented with reading tests to assess functional visual improvements. The direction of the fast phase and/or slow phase significantly affects RS. This could be because reading is an asymmetric task; English text reading is from left to right. Therefore right beating nystagmus fosters faster reading speeds (see figure). The “controlled” pendular waveform and difference in frequency suggests that these volunteers are able to modulate their waveform during reading, thus voluntary control of nystagmus occurs during reading. CR: M.G. Thomas, None; F.A. Proudlock, None; R.J. McLean, None; I. Gottlob, None. Support: NERC foundation, Wolfson foundation & Wellcome foundation Purpose: To assess the validity of the tenotomy procedure in patients with infantile nystagmus in terms of visual acuity and nystagmus intensity. Methods: Eye movements (500Hz) and LogMAR visual acuities were recorded from 6 patients with infantile nystagmus before and after a tenotomy procedure was performed. Eye movements and visual acuity (VA) were recorded at distance (1.2m) and near (0.4m) for 4 patients with albinism and nystagmus (1 of which had combined tenotomy/strabismus surgery) and 2 patients with idiopathic periodic alternating nystagmus (PAN). Nystagmus intensity was measured at positions from -30° to 30° eccentricity (for both 1.2m and 0.4m) at 3° intervals along the horizontal plane and the data was compared before and after (1wk, 4wks, 8wks, 12wks) surgery. Changes in intensity were viewed at null point and across all positions and compared to changes in VA. The patients’ own subjective estimates of change in VA and nystagmus were also recorded. Results: In terms of LogMAR VA the albinism patients improved by 13.8%, 17.8% and -3.5% for distance and 15.3%, 14.8% and 12.6% for near. The combination tenotomy/ strabismus patient improved by 3.4% for distance and 18.8% for near. The amount of improvement appeared to be dependent upon gaze position. Both PAN patients showed no change in VA. Variable changes were found on eye movement recordings, particularly reduction of nystagmus intensity on lateral gaze. All patients felt subjectively that their nystagmus had improved and all but one patient felt they had an improvement in VA. Conclusions: Early reports suggest that tentomy may improve infantile nystagmus. However, it is necessary to evaluate more patients to substantiate these findings and find which patients respond best to the procedure. CR: R.J. McLean, None; A. Kumar, None; F.A. Proudlock, None; I. Gottlob, None. Support: Ulverscroft Foundation Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 2831-2834 Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2827 - 2840 / A82 - A95 323. Nystagmus Organizing Section: EY 2835 - A90 Dynamic Improvements in Visual Function After the Tenotomy and Reattachment Procedure: Model Predictions and Patient Data 2836 - A91 Investigating the Veracity of a Commercial, Non-Medical, Magnetic “Treatment” for Infantile Nystagmus Syndrome L.F. Dell’Osso1,2, Z.I. Wang1. 1Daroff-Dell’Osso Ocular Motility Laboratory, Dept of Veterans Affairs Medical Ctr and CASE School of Medicine, Cleveland, OH; 2 Neurology and Biomedical Engineering, Case Western Reserve University, Cleveland, OH. J.B. Jacobs1,2A, Z.I. Wang1, K. Liao1, L.F. Dell’Osso1,2B. 1Daroff-Dell’Osso Ocular Motility Lab, Dept of Veterans Affairs Medical Ctr and CASE School of Medicine, Cleveland, OH; ANeurology, BNeurology and Biomedical Engineering, 2Case Western Reserve University, Cleveland, OH. Purpose: Infantile nystagmus syndrome (INS) patients often cannot quickly locate new visual targets (they are “slow to see”) or visually track moving objects (they cannot “catch up”). Dynamic demands on visual function are not measured by static measures, e.g., visual acuity; they require time-sensitive measures. We investigated how the dynamic properties of INS, saccadic latency (Ls) and both stationary (saccadic) and pursuit target-acquisition times (Lt), were affected by the tenotomy and reattachment (T&R) procedure. We used our behavioral ocular motor system (OMS) model to predict the responses of subjects with INS. Methods: We compared the pre- and post-T&R responses of 4 INS subjects with different INS waveforms to test the model’s predictions. Infrared reflection was used for one INS subject, high-speed digital video for three. We analyzed the human subjects’ responses to large and small target-step and ramp stimuli. Ocular motor simulations were performed in MATLAB Simulink and analysis in MATLAB using OMtools software (downloadable from omlab.org). Results: Ls values were typically slightly higher than normal and unaffected by T&R. Saccadic and pursuit Lt values were a function of when in the INS cycle the moving stimuli occurred and were decreased by the T&R procedure. Model outputs and predictions accurately simulated human data. During smooth pursuit, stimuli occurring near intrinsic saccades resulted in steady-state errors in both the predicted model outputs and patient responses. Conclusions: Intrinsic saccades disrupt the OMS’ ability to accurately calculate saccade amplitude and either refoveate or pursue targets. The T&R procedure reduces both stationary and pursuit target-acquisition times. OMS model simulations predicted novel stimulus-based effects on both types of target acquisition time in INS. Our model demonstrated emergent behaviors and predicted the therapeutic effects of T&R. The dynamics of INS foveation in INS-subject responses to changes in target position and velocity corresponded to both of the above patient complaints and to our model predictions. CR: L.F. Dell’Osso, None; Z.I. Wang, None. Support: Dept of Veterans Affairs Merit Review Purpose: Infantile nystagmus syndrome (INS) often leads to reduced visual acuity because of impaired ability to maintain stable gaze. Although INS cannot be cured, there are several accepted treatments - surgical, optical, and pharmacological - which have undergone rigorous scientific study for many years. Recently, advertisements have appeared for magnetized earrings that have been purported (among other claims) to improve the vision of people with INS. We cannot dismiss this out of hand, as (dubious benefits ascribed to “magnetism” aside) this could hypothetically make use of the same mechanism that we have previously shown to be a major contribution of contact lenses and other afferent stimulation of the trigeminal nerve (exteroception), similar to the mechanism (proprioception) hypothesized to underlie the therapeutic effects of nystagmus surgery. Methods: We recorded fixation eye movements from five patients with INS, at gaze angles from 30° left to 30° right, in 5° increments. Data were sampled at 500 Hz, using digital video. Subjects were calibrated monocularly to determine alignment and viewing eye(s), and tested under four conditions: baseline, clip-on earring, purpose-sold magnet earring, and high-strength, rare-earth magnets. The patients were not told the significance of each testing condition prior to the recording session. We used the expanded Nystagmus Acuity Function (NAFX) to analyze the foveation characteristics of nystagmus waveforms and thereby determine best potential visual acuity under each test condition. Results: Gross visual inspection of the nystagmus waveforms showed no difference between the control condition and the other trials for any subject. No subject reported any perceptual difference between the four conditions, either visual or how their nystagmus “felt.” NAFX analysis did not show significant differences between the control and any of the three ear-stimulus conditions. Conclusions: Although a previous study reported positive results (reduced nystagmus) following application of magnetic earrings, the findings are questionable as there were not sufficient control or alternative testing conditions, nor was a rigorous analysis of the nystagmus waveform performed using a quantitative, foveation-based method. Instead, findings relied on patient reporting, and a visual acuity exam that may have been affected by other factors. Correcting for these factors, no demonstrable improvements in the subjects’ nystagmus was found. CR: J.B. Jacobs, None; Z.I. Wang, None; K. Liao, None; L.F. Dell’Osso, None. Support: VA Merit Review 2837 - A92 Eye Muscle Surgery for Infantile Nystagmus Syndrome (INS) in the First Two Years of Life 2838 - A93 Convergence Dampening of Infantile Nystagmus Syndrome and its Relationship to Heterophoria R.W. Hertle1, J. Felius2, D. Yang1, M. Kaufman 3. 1Ophthalmology, Childrens Hospital of Pittsburgh, Pittsburgh, PA; 2Department of Ophthalmology, University of Texas Southwestern Medical Center, Retina Foundation of the Southwest, Dallas, TX; 3 Ophthalmology, Childrens Hospital of Pittsburgh, The University of Pittsburgh School of Medicine, PA. R.P. Rumpf, Z. Tai, R.W. Hertle, D. Yang. Ophthalmology, The Ocular Motor Neurophysiology Laboratory, The UPMC Eye Center, Department of Ophthalmology, The Children’s Hospital of Pittsburgh and The University of Pittsburgh, Pittsburgh PA 15213, Pittsburgh, PA. Purpose: We characterize the effects of eye muscle surgery in a young cohort of patients with INS. Methods: This is a prospective, comparative, interventional case series of 19 patients. All had an associated head posture or strabismus. All had two virgin recti on each eye operated on with some having a superior or inferior oblique muscle surgery for a chin up or down posture. All patients were followed for a minimum of 12 months. Outcome data and measures were obtained clinically with Teller acuity testing and with eye movement recordings and included: demography, associated eye/systemic conditions and Pre- and Post-Operative; Binocular Best Corrected Teller Acuity (BCTA), Anomalous Head Posture (AHP), Strabismic Deviation (SD), null zone width (NZW) and Nystagmus Optimal Foveation Fraction (NOFF), absolute foveation time (FOV) and null zone waveform changes (NZW). Results: Patients ranged in age from 5-23 mos (ave 17.4 mos), follow up averaged 14.0 mos, 8 had associated systemic disease, preoperative head postures in 13 (68%) ranged from 15 to 35 degrees. The most common associated ocular conditions were strabismus in 15 (79%), ammetropia in 13 (68%), and amblyopia in 9 (47%) and optic nerve, foveal or generalized retinal disease with or without albinism in 15 (79%). Regardless of the amount of head posture in degrees, after surgery, all patients significantly (p < 0.05) improved in AHP. There were significant (p <0.05) improvements, SD, NOFF. FOV and NZW. Group mean BCTA significantly improved (p<0.03). There were none who required a second operation and only a conjunctival suture related cyst occurred in two eyes. Conclusions: This study provides evidence that extraocular muscle surgery in the first two years of life in patients with INS waveformsfavorably changes their head posture, vision and nystagmus characteristics. Thus adding further evidence that eye muscle surgery positively affects the oscillation of INS and subsequent function CR: R.W. Hertle, None; J. Felius, None; D. Yang, None; M. Kaufman, None. Support: FFS PED0403 Purpose: Convergence dampening (CD) is often observed in patients with Infantile Nystagmus Syndrome (INS). However, it is not clear why it occurs only in some of the patients and not in others. To better understand the mechanism of the CD, we investigated the relationship between the CD and heterophoria in two groups of patients with and without CD. Methods: Six INS patients were recruited. Eye movements were measured using a video-based eye tracking system (EyeLink 1000 desktop). First, the CD was identified in a near/far viewing paradigm where patients alternatively looked at two targets, one at 30 cm and the other 150 cm from the eyes. The alternate duration was 5 seconds. Then heterophoria for each patient was measured using an alternate cover test in a fixation paradigm where patients fixated on a 0.5 degree target at 150 cm for one minute. The relationship between heterophoria and CD was analyzed with relation to visual acuity, binocular function and degree of clinically observed heterophoria. Results: Of the six patients recruited, five showed horizontal heterophorias and are listed in group A and one patient who did not show any heterophoria was put into group B. In group A, 100% of patients demonstrated an observable change in eye movements, as evidenced by eye movement recordings, with either convergence or divergence. Of these five patients, 3 showed convergence dampening and 2 showed divergence dampening. In contrast, CD was not obvious in group B. Conclusions: The presence of a heterophoria seems to contribute to the CD although other central neural mechanism may be involved. CR: R.P. Rumpf, None; Z. Tai, None; R.W. Hertle, None; D. Yang, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 2835-2838 Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2827 - 2840 / A82 - A95 323. Nystagmus Organizing Section: EY 2839 - A94 A Novel Mutation of the FRMD7 Gene in an Indian Family with X-linked Congenital Nystagmus 2840 - A95 Ferm Domain Containing 7 (frmd7) Expression in Developing Murine Tissues B. Chhunchha1A, R. Singh2, R.V. Mandava1B, S.K. Nath 3, U. Ratnamala4, U. Radhakrishna4. A Department of Zoology, BZoology, 1School of Sciences, Gujarat University, Ahmedabad, India; 2Dr. P.L. Desai Eye Center, Ahmedabad, India; 3Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, 825 N.E.13th Street, Oklahoma City, OK; 4Cancer centre, Creighton University, Omaha, NE. Purpose and Methods: Congenital nystagmus (NYS) is characterized by bilateral, and uncontrollable, involuntary movement of the eyes; its frequency is ~1:1500 live births. It is one of the most common neuro ophthamalological disorders among live births, and also reduces visual acuity. Nystagmus is transmitted in X-linked dominant, X-linked recessive and autosomal dominant forms with high penetrance and variable expressivity. Four NYS genomic locations (NYS1, NYS2, NYS3 and NYS4), mapped to Xq26.2, 6p12, 7p11.2 and 13q31-q22 respectively using family-based linkage analysis have been documented. Very recently, ~30 mutations of the FRMD7 gene, which maps to Xq26.2 region, have been found in NYS patients, suggesting that this gene plays an important role in the NYS development. Results & Conclusions: We report a novel mutation of the FRMD7 in a large elevengeneration Indian pedigree with an isolated non-syndromic NYS in which 62 members affected by NYS with different phenotypic expression including asymmetric pendular eye movements with unidirectional jerky NYS and head nodding. The missense mutation, c.A917G, predicts a substitution of Arg for Gln at codon 305 (Q305R) within exon 10 of FRMD7. This mutation was found to be at a highly conserved residue within the FERM adjacent (FA) domain, hypothesized to have a regulatory function, based on similarity to other protein kinase substrates. A detailed data of the present family and mutation spectrum of FRMD7 gene will be presented. CR: B. Chhunchha, None; R. Singh, None; R.V. Mandava, None; S.K. Nath, None; U. Ratnamala, None; U. Radhakrishna, None. Support: None T.E. Preston1, J. Self 1, H.M. Haitchi2, X. Chen1, A. Lotery1. 1Clinical Neurosciences, Clinical Neurosciences Division, Southampton, United Kingdom; 2Division of Infection, Inflammation and Repair, Roger Brooke Laboratory, Southampton University, United Kingdom. Purpose: To assess the temporal expression profile of the FRMD7 gene during the development of murine brain, lung and heart tissue. Background: Mutations in the FRMD7 gene are known to cause some cases of Congenital Idiopathic Nystagmus (CIN). Little is known about the pathophysiology of CIN or the function of this gene. Studies have indicated very low levels of gene expression in most human tissues with highest levels found in kidney. Results obtained using in situ hybridization have localized some expression to structures in the developing human embryonic brain. Funding for this research wasmade possible by the Nystagmus Network and the Gift of Sight appeal. Methods: Heart, lung and brain tissues were obtained from MF-1 mice at 11 developmental time points between embryonic days 11 and post natal day 8 and from adult mice. cDNA was extracted from these tissues and the relative expression of mRNA was calculated using quantitative real-time PCR techniques with GAPDH and ACTB normalising genes. Results: Expression of FRMD7 was found to be low in all three tissues with no significant variation seen in heart and lung tissues between ED11 and PD8, although there was a significant rise in the adult samples. However a significant increase was observed at ED18 in brain tissue. Conclusion: An increase in the expression of FRMD7 mRNA was seen at ED18 in murine brain contrasting with low level expression in heart and lung samples. Genes expressed during murine brain development are known to show temporal functioning clustering so it is possible to compare this expression profile with other genes and gene clusters expressed in the developing murine brain. Genes involved in formation and function of synapses and axon growth and guidance show the same temporal pattern as FRMD7 mRNA suggesting a similar role for the FRMD7 protein. These results suggest potential candidates for protein-protein interaction studies. They also help direct future work using an antibody to the FRMD7 protein. CR: T.E. Preston, None; J. Self, None; H.M. Haitchi, None; X. Chen, None; A. Lotery, None. Support: Nystagmus Network and Gift Of Sight Appeal Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 2839-2840 Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81 325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY 2873 - A58 Eye Movement Responses to Unilateral and Bilateral Otolithic Stimulation From Bone Conducted Sound 2874 - A59 Effects of Callosotomy on Nasotemporal Smooth Pursuit in Macaque Monkey: Validating a Cerebral Gaze Asymmetry Mechanism E.D. Cornell1A, A. Burgess1B, H.G. MacDougall1B, I.S. Curthoys1B. AFaculty of Health Sciences, BFaculty of Science, 1University of Sydney, Sydney, Australia. L. Tychsen1A, D. Sarezky1B, J. Leonard1C, P. Foeller1A. AOphthal and Neurobio-Childrens Hosp, BOphthalmology, CNeurosurgery, 1Washington Univ Schoof of Medicine, St Louis, MO. Purpose: Air conducted sound (ACS), delivered through headphones, and bone conducted vibration (BCV) of the head stimulate otolithic receptors in the inner ear and can evoke short latency vestibular induced extraocular muscle potentials (oVEMPs) recorded by electrodes beneath the eyes, that peak at approximately 10 ms. Studies using scleral search coils have confirmed, in a few subjects, the presence of small predictable eye movements following very short duration ACS and BCV. We sought to test whether longer duration BCV stimuli delivered to the mastoids unilaterally and bilaterally induced consistent eye movements and the effect of eye position on the movement. Methods: Bone conducted tone bursts at 500Hz with a duration of 150 ms and an inter-stimulus interval of 900ms were delivered at the mastoid unilaterally and bilaterally to healthy subjects using B71 bone conductors that were held in place by a latex cap while the subject’s eyes were directed to various positions. The resulting eye movements were recorded using 250Hz high resolution fire wire cameras. Results: A very small response at 10ms post stimulus could be detected in some subjects that was consistent with previous oVEMP responses. However this was followed by a much larger and more sustained response. Eye movements following unilateral stimulation were up to 0.35o (vertical) and 0.26o (horizontal), with a latency of around 25ms and with peak amplitudes at approximately 125ms post stimulus. The stimulus caused eye elevation for fixation positions towards the stimulated mastoid and depression for fixation positions opposite the stimulated mastoid. Horizontal responses were towards the stimulated mastoid. With bilateral stimulation the response was effectively a summation of unilateral movements: the vertical component increased (up to 0.57o) and the horizontal component was reduced or eliminated. Conclusions: Bone conducted vibration to the otoliths produces predictable horizontal and vertical conjugate eye movements that are gaze position dependent. CR: E.D. Cornell, None; A. Burgess, None; H.G. MacDougall, None; I.S. Curthoys, None. Support: None 2875 - A60 Effects of Earth-Fixed vs Head-Fixed Target on Ocular Counterroll M. Chandrakumar, Z. Hirji, A. Blakeman, H. Goltz, G. Mirabella, A. M. Wong. Ophthalmology and Vision Sciences, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada. Introduction: Ocular counter-roll (OCR) generates compensatory torsional eye movements during static head tilt. OCR is important from a clinical standpoint, because it explains the abnormal compensatory head tilt in patients with trochlear nerve palsy, and it forms the basis of the Bielschowsky head-tilt test. However, Jampel and Shi1 challenged the existence of OCR. One possible explanation for their1 failure to detect any OCR response may be their use of a head-fixed target. When a target moves with the head, the vestibulo-ocular reflex (VOR), including OCR, must be nulled to stabilize the target image on the fovea. The purpose of this study was to investigate whether OCR gain is reduced during viewing of a head-fixed target, as compared to an earth-fixed target, in healthy subjects. Methods: Twelve normal subjects were recruited. The target consists of a central fixation cross against a high-contrast grid pattern at 33 cm. The target was mounted on a vertical wall (earth-fixed), or coupled to the head (head-fixed). Eye movements were recorded using a video-based system. Changes in mean torsional eye position were plotted as a function of head position steps (0±25 deg in 5 deg steps) and fiveparameter sigmoidal fits were performed. Mean OCR gains were calculated by taking the derivative of the fitted functions. Results: Mean OCR gain with a head-fixed target (-0.084) was 40% lower than that with an earth-fixed target (-0.141; p < 0.0001). Conclusion: The partial decrease in OCR gain during viewing of a head-fixed target indicates that OCR is suppressed when a target moves with the head. This OCR gain reduction may result from suppression of the VOR by a central process. References: 1. Jampel RS, Shi DX. The absence of so-called compensatory ocular countertorsion: the response of the eyes to head tilt. Arch Ophthalmol 2002; 120: 1331-1340. CR: M. Chandrakumar, None; Z. Hirji, None; A. Blakeman, None; H. Goltz, None; G. Mirabella, None; A. M. Wong, None. Support: MSH 55058, MOP 152588 and MOP 57853 Purpose: Knowledge to date regarding horizontal gaze control in primates indicates that smooth eye tracking is driven by neurons in the medial-superior-temporal (MST) area of each cerebral hemisphere. The directional organization is ipsiversive: MST of the right hemisphere drives rightward tracking and MST of the left hemisphere, leftward tracking. Visual motion neurons of areas V1/MT must send feed forward projections--representing rightward vs. leftward motion from each visual hemi field--to the appropriate MST, presumably through the splenium (posterior quarter) of the corpus callosum. Convolving visual hemi fields on rightward vs. leftward motion, callosotomy would be expected to disrupt tracking of stimuli moving away from the vertical meridian within each hemi field (centrifugal motion), but spare tracking of stimuli moving toward the vertical meridian (centripetal motion). To test this prediction, we performed a partial callosotomy. Methods: The splenium (i.e. posterior portion) of the callosum was sectioned in a 1 yr old monkey. The rostrum, genu and body of the callosum were left intact. Several weeks later, horizontal step-ramp motion stimuli were confined to the right or left visual hemi fields to elicit centripetal vs. centrifugal smooth pursuit when viewing with either eye monocularly. Results: Smooth eye velocity evoked by ramps of stimulus motion revealed decrements in gain of ~ 20% for centrifugal motion within each hemi field. The response to centripetal motion was unaffected. Latencies for centrifugal motion were prolonged (~20%) when compared to those for centripetal motion. Saccadic latency and accuracy was unaffected. Conclusions: Sectioning of the callosal splenium produced the predicted asymmetry of pursuit, but the effect was underwhelming. Two interpretations are possible: 1) the sectioning may have been less complete than assumed, or 2) visual projections from areas V1/MT travel through more anterior regions of the callosum (e.g. the body as well as the splenium). Further experiments will be necessary to establish the validity of these interpretations. CR: L. Tychsen, None; D. Sarezky, None; J. Leonard, None; P. Foeller, None. Support: NIH Grant EY10214 (LT,PF) 2876 - A61 The Effect of Amplitude and Interval on Ocular Torsion When Viewing Rotating Images U. Sverkersten, G. Öqvist Seimyr, T. Pansell, S. Abdi, J. Ygge. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Purpose: When an image containing spatial information is tilted, it induces more compensatory ocular torsion than an image without spatial information (Pansell, Sverkersten & Ygge, 2006). The aim of the present study was to investigate the effect of amplitude (of image rotation) and interval (image rotation frequency) on visually induced ocular torsion. Methods: Ocular torsion was recorded in five healthy individuals using a head mounted video oculography system (Chronos vision, Germany). The stimulus consisted of an image showing a city scene rich in spatial orientation cues. Centered on the image was a fixation point which the subject was instructed to look at. The stimulus was displayed on a computer screen (1600x1200 @ 60Hz) at a distance of 50 cm. After ten seconds, the image started to rotate (clockwise) around the fixation point in steps of 3.75°, 7.5° or 15° at intervals of 1.5, 3 or 9 seconds. The image continued to rotate in steps for 60 seconds. The rotations had a smooth acceleration and deceleration phase and lasted one second. All subjects viewed all combinations of amplitudes and intervals in a randomized order. Between each of the nine conditions there was a washout period when nothing was displayed on the screen for 30 seconds. Results: An immediate transitory torsional response was found for each stimulus rotation. The 15 degree amplitude induced a larger transient response (2.40± 0.16 deg) compared to the 7.5-degree (1.8±0.19 deg) and the 3.75-degree (1.38±0.12 deg) rotations. In the tests with short time intervals, the torsional position was accumulated over time, shifting the torsional position in the same direction as the stimuli (maximum 5 deg). In the tests with longer time intervals the torsional position returned towards the initial reference position before the next stimuli took appeared. Conclusions: A larger stepwise rotation induced a larger torsional response. The time interval between rotations had little influence on the transient torsional response. However, a short time interval induced a shift of the torsional position, something which was not seen at longer time intervals. CR: U. Sverkersten, None; G. Öqvist Seimyr, None; T. Pansell, None; S. Abdi, None; J. Ygge, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 2873-2876 Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81 325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY 2877 - A62 Ocular Torsion and Associated Head Movement in a Flight Simulator 2878 - A63 Test-Retest Reliability of Saccadic Measures S. Gowrisankaran, N. Fogt. Vision Science, Ohio State University, Columbus, OH. T.M. Blekher1A, M.R. Weaver1B, J. Marshall1B, J. Wojcieszek1C, L. Flury-Wetherill1B, R.D. Yee1A, T.M. Foroud1B. AOphthalmology, BMedical and Molecular Genetics, C Neurology, 1Indiana University School of Medicine, Indianapolis, IN. Purpose: In previous studies, head tilt in the direction of a tilting horizon has been demonstrated in a flight simulator. Torsional eye movements during movement of the horizon in a flight simulator have not been examined. The purpose of this study was to measure ocular torsional responses to a moving horizon in a static flight simulator. Methods: 5 subjects (18-35 yrs) participated. Subjects viewed a projected scene (of the sky and the ground) in a dark room. Eye and head movements were recorded using a video tracker and a magnetic sensor respectively. 10 trials were recorded for each subject. In each trial subjects tilted the airplane/horizon (using a joystick) randomly to the right or left away from the horizontal meridian (aligning tilt), and returned the plane to a non-tilted horizontal position (realigning tilt). The movement of the horizon was recorded. The average frequency of these sinusoidal movements was 0.3 Hz. Results: 3D eye and head movements for 20 blink free (20 aligning and 20 realigning tilts) trials were analyzed. The average magnitude of aligning tilt was 48deg and was 55deg for the realigning tilt. An ocular torsional response occurred with tilt of the horizon in 32 out of 40 cases. Head tilts (always in the direction of horizon tilt) occurred in 28 of the 40 cases analyzed. The average head tilt was 11.7deg for the aligning tilt and 8.7deg for the realigning tilt. Regardless of whether the head moved the typical torsional response was a high velocity movement in the same direction and faster than the horizon tilts, with an amplitude gain of 0.07. This was followed by a drift opposite to the initial movement. The average fast phase amplitude was 3.9 deg (aligning tilt), and 3 deg (realigning tilt). Conclusion: Small, high velocity torsional eye movements occurred in the direction of horizon tilt with and without head movements. These torsional eye positions were not sustained. If ocular counter-roll occurred with head movement, it did not completely cancel the high velocity torsional movement. In a static flight simulator, individuals make high velocity torsional movements in the direction of horizon tilt that are different from the following responses generated in previous studies in response to full-field torsional rotation of the visual scene. CR: S. Gowrisankaran, None; N. Fogt, None. Support: Naval Aerospace Medical Research Laboratory 2879 - A64 Cortical Areas Involved in Vertical Saccades With a 3 Teslas Functional Mri J. Beynat1A, S. Bidot1A, P. Quercia1A, F. Ricolfi1B, T. Pozzo2, A.M. Bron1A, C. CreuzotGarcher1A. ADepartment of Ophthalmology, BDepartment of Neuroradiology, 1 University Hospital, Dijon, France; 2Inserm u887, University of Burgundy, Dijon, France. Purpose: The aim of this study was to assess the activation of the cortical eye fields involved in vertical and horizontal saccades with a 3 teslas functional MRI. Methods: Eight healthy right-handed subjects (6 men and 2 women) participated in the study. The tasks tested 2 different types of saccades: “visually guided” and voluntary. For each one, we compared cortical eye fields activation during vertical axis eye movements with those activated during horizontal axis movements. The acquisition of the data was carried out via the Neuro 3D software (Siemens, Germany). Statistic data treatment was carried out using FSL software (FMRIB Software Library) according to the General Linear Model (GLM). The analysis of the pictures was done with MRIcro software (v 1.4, Chris Rorden, the United Kingdom). Results: Picture analysis was realized with the group analyses maps, and with the substraction maps. For each type of saccades, we could find the activation of most cortical areas involved in eye movements; the Frontal Eye Field (FEF), the Supplementary Eye Field (SEF) and the Posterior Parietal Cortex (PPC). An activation of the superior parietal cortex (7th Brodmann area) was observed for both types of vertical saccades. In addition, we found a specific activation of the right DorsoLateral PreFrontal Cortex (DLPFC) during voluntary vertical saccades. Conclusions: Our study allowed to identify the various activated cortical eye fields according to the saccades direction. The superior parietal cortex and the DLPFC seem to be particularly involved during vertical saccades. CR: J. Beynat, None; S. Bidot, None; P. Quercia, None; F. Ricolfi, None; T. Pozzo, None; A.M. Bron, None; C. Creuzot-Garcher, None. Support: None Purpose: Abnormalities in saccades appear to be sensitive and specific biomarkers in the pre-diagnostic stages of Huntington disease (HD) The goal of this study was to evaluate test-retest reliability of saccadic measures in prediagnostic carriers of the HD gene expansion (PDHD) and normal controls (NC). Methods: The study sample included 12 NC and 9 PDHD who completed two study visits within an approximately one month interval. At the first visit, all participants completed a uniform clinical evaluation. A high resolution video-based system was used for recording eye movements during completion of the battery of visually guided, anti-saccade, and three memory guided tasks. Measures of the saccades (latency, velocity, gain, and percentage of error saccades) were quantified. Test-retest reliability was evaluated by calculating the intraclass correlation (ICC) of the saccade measures collected at the first and second visits. Additionally, regression analysis was used to evaluate the influence of age, gender, and group (NC or PDHD) on difference in measures between visits. Results: Percentage of error saccades showed good test-retest reliability in antisaccade and memory guided tasks (average ICC=0.8, p<0.001). The latency of saccades also demonstrated good test-retest reliability (averaged ICC=0.74, p< 0.02) across all tasks. The velocity and gain of saccades showed moderate reliability (ICC~0.5). ICC was similar in NC and PDHD groups for most measures. There were no significant group, age, or gender effects when analyzing the difference in each saccade measure between the first and second visit. Conclusions: Good test-retest reliability of saccadic latency and percentage of errors in anti-saccade and memory guided tasks suggests that these measures could serve as potential biomarkers to evaluate progression in HD. CR: T.M. Blekher, None; M.R. Weaver, None; J. Marshall, None; J. Wojcieszek, None; L. Flury-Wetherill, None; R.D. Yee, None; T.M. Foroud, None. Support: R21NS060205, the CHDI Foundation, and an unrestricted Grant from RPB, Inc. to the Department of Ophthalmology, IU Medical School. 2880 - A65 Saccades and the Muller-Lyer Illusion: Effect of Previews and Saccade Inhibition P.C. Knox. Orthoptics, University of Liverpool, Liverpool, United Kingdom. Purpose: Saccade amplitude is modified by the Muller Lyer (ML) illusion in the same manner and to the same extent as perception, even when pointing is not affected (Bernadis et al, 2005, Exp Brain Res 162:133). This is contrary to the predictions of the “two visual systems” hypothesis. However, the type of saccade, display characteristics and subject instructions, all play a role in the size of effects observed. Here, the effect of the ML illusion on saccade amplitude, in circumstances in which subjects had to suppress reflexive responses, was investigated with two display times (200ms and 1000ms). Methods: Twelve subjects were exposed to ML displays with one vertex at fixation and the other displayed eccentrically to left or right (6° separation between vertices). “In” (><), “out” (< >) and control (xx) configurations, direction and display time (200ms vs 10000ms) were interleaved. Subjects were instructed not to saccade until the display was extinguished. Eye movements were recorded with infrared oculography and primary saccade amplitude and latency measured offline. Only saccades with a latency from target offset of >100ms and an amplitude >3° were included in the analysis. Results: Two subjects’ data were not analysed for technical reasons. For both display times, the remaining 10 subjects suppressed reflexive saccades, and responded to the target offset, at the cost of increased latency (time from offset, 200ms: latency = 381±45ms; 1000ms: 305±40ms; t=4, p<0.0001; Fig A). For both display times, saccade amplitudes increased with the “in” and decreased with the “out” configuration. Effect size calculations (In-Out/Control, expressed as %) showed a trend towards larger effects with the 1000ms display time (200ms: 18±5% vs 1000ms:23±9%; t=1.6, p=0.06; Fig B). Conclusions: Saccade amplitude was modified by the ML illusion, in the same manner and to a similar extent, as perception in these experiments. The effect of an extended preview period was to decrease saccade latency, and increase illusion effect size. However, the effect sizes were similar to what we have reported previously for both reflexive and memory guided saccades (Knox & Bruno, 2007, Exp Brain Res 181:277). These results are not compatible with any strong version of the two visual systems hypothesis. CR: P.C. Knox, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 2877-2880 Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81 325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY 2881 - A66 Fourier Transformation Reveals a New Fixational Eye Movement 2882 - A67 Effects of Caffeine on Fixational Eye Movements B. Zhang1, T. Pansell1, J. Ygge1, S. Giovagnoli2, R. Bolzani2. 1Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 2Department of Psychology, University of Bologna, Bologna, Italy. N.E. Collins1,2A, M. AlKalbani2A,1, P. Kavanagh 3, A. Mahmud 3, G. Boyle2B, D. Coakley2A,1. 1 Medicine, Trinity College Dublin, Dublin 2, Ireland; AMercer’s Institute for Research on Ageing, BMedical Physics and Bioengineering, 2St James’s Hospital, Dublin 8, Ireland; 3Dept. of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, St James’s Hospital, Dublin 8, Ireland. Purpose: A slow periodic oscillation of the eye position occurring during visual fixation has been identified. To our knowledge, this type of eye movement has not been described before. The aim was to describe its characteristics. Methods: Eye movements were recorded binocularly in six healthy subjects. In test 1 the effect of three different recording techniques was analyzed: infrared corneal reflection technique with head mounted goggles (XY1000, IOTA Inc.); head mounted video oculography (VOG; Chronos Vision); and Scleral Search Coil (SSC: Skalar Inc.). In test 2 the effect of sampling frequency was evaluated by using the SSC with different sampling frequencies (120, 140, 160, 180 and 200 Hz). The eye position data was band-pass filtered (0.05-0.15) and the oscillatory components of the eye position were evaluated by a fast fourier transformation (FFT). Results: A consistent finding in all test subjects and recordings was a slow periodic oscillation of eye position i.e. the eye position oscillated (amplitude ±0.5 deg) in a horizontal-vertical elliptical track. The duration of a complete oscillation was approximately 10 seconds. The FFT analysis thus revealed an prominent peak value (~0.1 Hz) with large intra-individual variation but small inter-individual variation, independent of recording technique, sampling frequency or related to blinking. Conclusion: A slow regular oscillation of eye position was demonstrated which does not seem to be an artefact due to recording technique, sampling frequency or blinking. The finding advocates new thoughts of the visual fixation mechanisms . The purpose of this new eye movement can at present not be explained but it might be involved in a light energy protective mechanism of the fovea. CR: B. Zhang, None; T. Pansell, None; J. Ygge, None; S. Giovagnoli, None; R. Bolzani, None. Support: None 2883 - A68 Oculomotor and Vestibular Performance in Children With Autism Spectrum Disorder. Purpose: To investigate the acute effect of caffeine on fixational eye movements (ocular microtremor and microsaccades). Ocular microtremor (OMT), a minute eye movement present at all times in normal subjects, is a measure of arousal in terms of reticularformation activity, and has been demonstrated as a potential measure of brainstem integrity in multiple sclerosis, coma and brainstem death. Drugs which alter arousal and alertness may affect OMT, and confound its measurement in the clinical setting. We investigated whether the common stimulant caffeine affects OMT, and whether it is a source of variability in studies of fixational microsaccades. Methods: The effect of a single oral dose of caffeine on ocular microtremor was examined in a randomised double-blind crossover study. Twenty healthy subjects were studied on two occasions at least a week apart, after ingestion of 350ml caffeinated (180mg) and decaffeinated (< 10mg) coffee, in randomized order. OMT recordings were made using the piezoelectric strain-gauge technique, at baseline, and at 30 minutes and 90 minutes after coffee ingestion. Results: Compared with baseline, there was a small but significant increase in OMT peak frequency at 30 minutes after caffeine ingestion from 85.9Hz (SD 3.4Hz) to 87.9Hz (SD 3.3) (95% CI for difference between means: 1.0Hz, 3.0Hz; p < 0.001). OMT frequency remained slightly elevated at 90 minutes after caffeine ingestion. No effect was seen with decaffeinated coffee. There was also a trend towards fewer microsaccades following caffeine ingestion, from 49.6 microsaccades/min at baseline to 36.2 microsaccades/min at 30 minutes, (95% CI for difference between means: -3.4, 30.2), although this did not reach significance (p = 0.111). Conclusions: The results demonstrate that the frequency of OMT is increased in response to caffeine. The increase in OMT frequency was relatively small, and not clinically significant in the context of previous studies of OMT. In studies of fixational eye movements where small differences in parameters are considered significant, caffeine should be taken into account as a potential source of variability. CR: N.E. Collins, None; M. AlKalbani, None; P. Kavanagh, None; A. Mahmud, None; G. Boyle, None; D. Coakley, None. Support: None 2884 - A69 Eye Movements Disorders in Glaucoma J.O. Phillips1A,2, D.E. Parker1A, C.M. Jacobs2, R.J. Groen1B, A.H. Weiss2, S.J. Webb1B. A Otolaryngology, BPsychiatry and Behavioral Sciences, 1University of Washington, Seattle, WA; 2Ophthalmology, Seattle Children’s Hospital, Seattle, WA. Purpose: A number of authors have hypothesized a relationship between cerebellar functioning and autism. Some studies have shown correlated changes in oculomotor behavior. This study compares the conjugate eye movements of children with autism spectrum disorder with those of normal age-matched controls. Methods: Children with autism spectrum disorder (ASD, n=13) and typical age matched control children (TYP, n=23) were tested on a range of eye movement tasks at Seattle Children’s Hospital. The average age of the subjects was 10.4 y. Subjects were assessed while holding gaze in the dark, fixating stationary point targets at different eccentricities, making saccades to pseuorandomly presented point targets, making sequential saccades to stationary targets in a patterned array, making anti-saccades, pursuing a sinusiodally moving point target, viewing a moving high-contrast full field grating (OKN), and during en-block rotation about a fixed vertical axis in the dark (VOR). Eye movements were recorded binocularly with an SMI videonystagmography system. All subjects were given the same instruction. Results: With three notable exceptions, ASD children had stable gaze holding in the dark and during fixation of eccentric targets. Saccades to stepped targets were highly variable in a subset of the ASD children, with many showing hypometric saccades of long duration. Smooth pursuit was variable overall, but ASD children on average had remarkably good pursuit performance. OKN was abnormal in ASD children only at higher target velocities. VOR had normal gain in most ASD children. The most dramatic differences were seen in the sequential saccade task and the antisaccade task. Children with ASD had consistently poorer performance than TYP children, despite demonstrating a clear understanding of the task. Conclusions: Taken together these results show clear differences between ASD and TYP oculomotor performance in children. However, the remarkably well-preserved smooth pursuit performance is not entirely consistent with cerebellar models of ASD. CR: J.O. Phillips, None; D.E. Parker, None; C.M. Jacobs, None; R.J. Groen, None; A.H. Weiss, None; S.J. Webb, None. Support: NAAR (Webb) C. Lamirel1,2, D. Milea 3, I. Cochereau4, M.H. Duong5, J. Lorenceau2. 1Ophthalmology, Centre Hospitalier Universitaire, Angers, France; 2Laboratoire de science cognitive et d’imagerie cérébrale, CNRS, Paris, France; 3Ophthalmology, Glostrup Hospital, Copenhagen, Denmark; 4Ophthalmology, Hopital Bichat, Paris, France; 5 Ophthalmology, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France. Purpose: To investigate disorders of eye movements in open angle glaucoma. Methods: Comparative study of saccades, pursuit and a saccade-pursuit sequence on a moving target in 3 groups: 4 patients with open angle glaucoma and a mild visual field defect (mean MD: -5dB, mean age: 51years); 4 patients with open angle glaucoma and an almost normal visual field (mean MD: -0.5dB, mean age: 57 years); and 4 age-matched control subjects (mean age: 54 years). Eye movements were recorded monocularly (right eye for all subjects) at 240hz using an ISCAN ETL-400 system (Burlington, MA, USA). Results: For the saccade task, the mean saccade latency was longer in glaucomatous patients (247 and 259 ms) than in the control group (236ms) (F(2,798)=18, p<10 -3). Mean saccade gain was lower in glaucomatous patients with visual field defect (81%) than in patients with almost normal visual field (86%) and in controls (89%) (F(2,798)=13 ; p<10 -3). During pursuit, maximum eye speed was faster in both groups of patients (31 et 28°/s) than in controls (21°/s) (F(2,2455)=68, p<10 -3). The mean pursuit and gain was similar in the 3 groups (105% for controls, 107% for normal visual field patients, 110% for patients with visual field defect) but speed variability of pursuit was larger in the 2 groups of glaucomatous (10 and 9°/s) than in controls (3°/s) (F(2, 2455)=18, p<10 -3). During the saccade-pursuit task the latency of the maximum’s speed of the saccade was longer in the 2 groups of patients (305 and 350ms) than in controls (283ms) (F(2, 1910)=103, p<10 -3). Saccade gain was smaller in glaucomatous patients (73 and 75%) than in controls (82%) (F(2, 1910)=23, p<10 -3). Speed variability of pursuit following the saccade was larger in glaucomatous patients (7 and 8°/s) than in controls (3°/s) (F(2, 1910)=54, p<10 -3). Conclusions: The larger variability and inaccuracy of eyes movements in glaucomatous patients suggest an alteration of eye movement control in this condition. These patients had lower performances in the saccade-pursuit task, which required analysis of the target speed in the peripheral visual field. Glaucoma also affects high order visuomotor functions, even if visual fields are preserved; suggesting that eye movements may be affected early in the disease CR: C. Lamirel, None; D. Milea, None; I. Cochereau, None; M.H. Duong, None; J. Lorenceau, None. Support: Fondation pour la Recherche Medicale, Fondation Berthe Fouassier, Fondation de France Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 2881-2884 Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81 325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY 2885 - A70 A New Scalable Computerized Random Dot Stereopsis Test 2886 - A71 The Distance Randot ® Stereotest Test: Normative Data and Validity R. Robilotto, G. Zikos, A. Selenow, S. Slotnick. Institute for Vision Research, Manhattan Vision Associates, New York, NY. E.E. Birch1,2, J. Wang1, S.R. Hatt3, A.R. O’Connor4, J.R. Drover5, J.M. Holmes3. 1Pediatric Eye Research Lab, Retina Foundation of Southwest, Dallas, TX; 2Ophthalmology, UT Southwestern Medical Center, Dallas, TX; 3Ophthalmology, Mayo Clinic, Rochester, MN; 4Orthoptics, University of Liverpool, Liverpol, United Kingdom; 5 Psychology, Memorial University, St. Johns, NL, Canada. Purpose: Stereopsis is exquisitely sensitive to many of the more subtle disturbances of the vision process, including uncorrected refractive error and sensory/motor fusion problems, making accurate measurements of stereoacuity is critical for both research and clinical purposes. We have developed a novel customizable computerbased random-dot stereoacuity test that overcomes many shortcomings of current clinical stereo testing, such as incomplete dissociation, memorization, and parallax. Our test can be presented on a standard CRT with direct viewing, or minimized on a back-projected screen using a high resolution DLP projector and relay optics. Here we compare the repeatability and reliability of the MVA Computerized RDS test to existing clinical stereo tests. Methods: Pairs of random-dot bitmap images were created in MatLab and displayed at 1600x1200 resolution at 5 meters. Image pairs were alternated at 80Hz and viewed though LCD shutter glasses oscillating in phase at the same frequency, completely dissociating the image pairs without residual monocular cues. Sets of RDS images were generated at 18cpd in approximately 0.125 log second steps from 9.9 - 237.6 seconds, and designed so that multiple sets of targets could be displayed on a single screen, reducing test time. Stereoacuity thresholds of six healthy presbyopic subjects (mean age 48.6yo) with normal binocularity were measured with best correction using our new MVA RDS test and compared to threshold measurements from currently available computerized RDS and stereo ring tests using red/green anaglyphs (Innova ProVideo). Six threshold measurements were taken on each test (3 measurements on two separate days) for each subject. Results: Across all subjects, the MVA RDS test provided lower threshold values (mean=38.5”) and lower standard deviation (mean SD=9.13”) than the clinical RDS (mean=44.0”; mean SD=21.1”, p=0.029) and stereo ring test (mean=68.6”; mean SD=23.0”, p=0.039). In terms of mean standard deviations as ratios of mean thresholds, the MVA RDS test provided lower ratios than the clinical RDS (p=0.007) and stereo ring test (p=0.044). Conclusions: The MVA computerized stereoacuity test is a repeatable, valid test that can incorporate a broad range of customized targets and can be scaled for different distances, including optical minimization for near testing. CR: R. Robilotto, None; G. Zikos, None; A. Selenow, None; S. Slotnick, None. Support: None 2887 - A72 Monovision: Consequences for Depth Perception From Fine and Coarse Disparities Purpose: Distance stereoacuity data may be useful in assessing strabismic patients who have differences in the distance and near angle of deviation, including intermittent XT. We developed the Distance Randot ® Stereotest as an easily administered quantitative test for distance stereoacuity in children as young as four years of age. Using a prototype, we previously reported extensive testability, validity, and normative data. Here we report normative and validity data for the final, commercially available version of the test. Method: The Distance Randot ® is a Polaroid vectographic book, presenting 2 shapes at each of 4 disparities: 400, 200, 100, and 60 arcsec viewed at 3m through polarizing glasses. The smallest disparity level at which the child can identify both shapes is recorded as stereoacuity. We administered the Distance Randot ® to 31 normal volunteers (4-36 y) and 39 strabismic patients (4-73 y). The prototype distance stereoacuity test was also administered. Test-retest data were collected for the final version of the test. Results: Normative Distance Randot ® scores were similar to those obtained with the prototype; 96.8% of normal scores were ≤100 arcsec. Test-retests were identical in 71% and within one disparity level in 96.8%. Among strabismic patients, 79.5% had abnormal Distance Randot ® scores; the few with normal scores had incomitant or intermittent deviations. Nil stereoacuity was found in 22 patients and confirmed in 90.9% of retests; 17 had measureable stereoacuity, confirmed in 91.4% of retests. Patients with constant ET or XT (n=16) were more likely to have nil stereoacuity than patients who had intermittent ET or XT (n=15)(100% vs 20%; z=7.75, p<0.001). Overall, Distance Randot ® scores were highly correlated with prototype scores (rs = 0.90, p<0.001). Conclusion: The tight clustering and high test-retest reliability of normative data results in little overlap with scores from patients who have significant binocular sensory disorders. Data from strabismic patients suggest that the Distance Randot ® Stereotest is a sensitive measure of binocular sensory status that may be useful in monitoring progression and/or recovery. CR: E.E. Birch, Stereo Optical Corporation, F; J. Wang, Stereo Optical Corporation, F; S.R. Hatt, Stereo Optical Corporation, F; A.R. O’Connor, Stereo Optical Corporation, F; J.R. Drover, Stereo Optical Corporation, F; J.M. Holmes, Stereo Optical Corporation, F. Support: EY05EY05236 (EEB) and EY015799 (JMH) 2888 - A73 Effect of Binocular versus Monocular Viewing on Golf Putting Accuracy C.E. Smith1A, L.M. Wilcox1A, R.S. Allison1B, O. Karanovic1, F. Wilkinson1A. ADepartment of Psychology, BDepartment of Computer Science and Engineering, 1Centre for Vision Research, York University, Toronto, ON, Canada. Purpose: Traditionally presbyopia is treated using corrective bifocal or multifocal lenses. An alternative is to correct one eye for near and the other for distance with a method known as “monovision”. It is known that differential interocular blur can degrade stereoacuity, and recent studies have confirmed that monovision treatment increases stereoacuity thresholds. However, stereoacuity tests do not assess disparity sensitivity in the coarse range. Given the proven link between stereopsis and stability, we have measured the short-term effects of induced monovision on stereopsis over a broad range of fine (fused) and coarse (diplopic) disparities at both near and far viewing distances. Methods: Stimuli were presented dichoptically using a time-sequential polarized stereoscopic display. During each trial a line was presented for 300 ms with either crossed or uncrossed disparity above a zero disparity fixation cross. Participants indicated the direction of the depth offset. In one session baseline performance was assessed with optimal optical correction. In another, monovision was induced by adding -1D and +1D lenses in front of the dominant and non-dominant eyes respectively. We assessed performance at distances of 62 and 300 cm in counterbalanced blocks. Within each block, the stimuli were presented at 5 fine disparities ranging from 60 to 2400 arcsec and 5 coarse disparities ranging from 1o to 3.5o. Results: Induced monovision resulted in decreased accuracy relative to baseline in the fine disparity range, but effects were minimal in the coarse range. Monovision also had a larger impact on performance at a viewing distance of 300 cm than at 62 cm. Conclusions: Induced monovision not only increases stereoacuity thresholds, but degrades depth discrimination across the range of fusable disparities in young observers. This effect on fine disparity is accentuated at larger viewing distances typical of fixation distances during walking, suggesting that stability during locomotion may be degraded. However, we also found that coarse stereopsis was relatively spared, and this may offset the observed losses. CR: C.E. Smith, None; L.M. Wilcox, None; R.S. Allison, None; O. Karanovic, None; F. Wilkinson, None. Support: The Canadian Institute for Health Research and York University R.C. Bulson, K.J. Ciuffreda, D.P. Ludlam. Department of Vision Sciences, SUNY College of Optometry, New York, NY. Purpose: To elucidate the role of binocular vision, including both stereopsis and vergence innervation, in the complex task of golf putting. Methods: The putting accuracy of sixteen, visually-normal inexperienced golfers (range 23-66 years, mean=35 years) was assessed for small (3cm) and large (12cm) targets located at 3, 6, and 9 feet with distance corrective lenses in place. All subjects had normal binocular vision with stereopsis less than 40 sec arc, were free from any ocular or neurological disease, and were visually asymptomatic. Subjects performed the task under either normal binocular or monocular viewing conditions. All testing was performed in a counterbalanced manner with respect to target size and viewing condition. Results: Putting accuracy (% successful putts) was significantly better under binocular versus monocular viewing conditions, especially for the smaller target. For the smaller target, putting accuracy was better under binocular versus monocular viewing conditions for 10 out of 12 (83%, p=0.019), 11 out of 12 (92%, p=0.003), and 12 out of 12 (100%, p<0.001) of the subjects for the 3, 6, and 9 foot test distances, respectively. The percentage improvement in putting accuracy under binocular viewing conditions for the small (3cm) target was approximately 14%, 8%, and 13% for the 3, 6, and 9 foot target distances, respectively. For the larger target, the trends were similar, but much smaller in magnitude (0.5-7%). Conclusions: These findings are consistent with earlier studies demonstrating improved athletic performance under binocular versus monocular viewing conditions. Binocular vision is an important factor in successful completion of a complex sensorimotor task, such as golf putting. The additional depth-related cues provided by stereopsis and vergence innervation appear to be crucial for more precise and detailed tasks, such as demanded by the smaller target. CR: R.C. Bulson, None; K.J. Ciuffreda, None; D.P. Ludlam, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 2885-2888 Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81 325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY 2889 - A74 Vergence Induced by Optic-Flow Motion in Patients With Strabismus 2890 - A75 Vergence and Three-Dimensional Perception Induced by Ground-Plane Motion D. Yang, E.S. Hald, R.W. Hertle, Z. Tai. Ophthalmology, Univ of Pittsburgh ChildrensHosp, Pittsburgh, PA. Z. Tai, R.W. Hertle, E.S. Hald, D. Yang. Ophthalmology, University of Pittsburgh, Pittsburgh, PA. Purpose: Subjects with strabismus have shown deficits in disparity vergence eye movements. We investigated how their damaged vergence system responded to optic flow motion in the ground plane. Methods: Backward/forward motion of a sinusoidal grating pattern which does not have horizontal disparity was displayed on a computer monitor in the ground plane and binocular movements were recorded with a video-based eye tracking system (EyeLink 1000 desktop). Subjects looked at the center of the pattern for 5 seconds in each trial and various velocities and two different directions were randomized. Openloop and closed-loop vergence velocities, amplitudes, and latencies were quantified and compared with normal subjects. Results: In normal subjects, involuntary horizontal vergence nystagmus was recorded. In patients, robust vergence nystagmus was also induced. The slow-phase velocity of open-loop vergence from strabimus subjects was higher than normal subjects and the latency of the initail responses was shorter than normal subjects. The closed-loop vergence from strabismus patients was as strong as normal subjects. Conclusion: The vergence system in strabismic patients is responsive to optic flow motion. The results suggest that optic flow motion may be independently processed in a different pathway and optic flow vergence may become dominant in daily vergence control in patients with binocular disparity processing damage. CR: D. Yang, None; E.S. Hald, None; R.W. Hertle, None; Z. Tai, None. Support: NIH grant EY015797, RPB and CMRF of University of Pittsburgh Purpose: A moving observer experiences optic flow stimulus during fore/aft movements. It is known that optic flow induced vergence eye movements to stabilize gaze (Yang et al 1999). However, disparity stimuli are also available to the moving observer in the real world and their effect on optic flow vergence is not clear. To study the effect of disparity on vergence induced by optic flow motion in the gound plane, we tested subjects with a modified grating pattern used to induce optic flow vegence (Yang et al 2007 and Zhu et al 2008). Methods: By interpolating sinusoidal grating stripes with reversed polarity on a sinusoidal grating pattern, a checkboard-like pattern was generated. The motion of the checkboard pattern or a sinusoidal grating pattern was displayed on a computer monitor in the ground plane and binocular movements were recorded with a videobased eye tracking system (EyeLink 1000 desktop). Three normal subjects looked at the center of the pattern for 8 seconds in each trial and they were instructed to press a gamepad button when they perceived a 3 dimensional (3D)layer in the pattern. All experimental conditions including various velocities, two patterns, and two directions were randomized. Vergence amplitudes, velocities, and latencies were quantitively analyzed. Results: Horizontal vergence in a form of optokintic nystagmus was induced by each pattern. In addition, a clear 3D layer was perceived by all 3 subjects when the checkboard pattern was used. The 3D perception occured 1.5-5 seconds after the initiation of the motion and it was usually associated with an brief increase in vergence. The latency and velocity of the initial open-loop responses were the same for the two different stimulus patterns. The velocity of closed-loop vergence was significantly increased by 20-30% when checkboard pattern was used. There was no increase in vergence with monocular viewing of checkboard pattern. Conclusion: A 3D perception was induced by disparity from motion in the groundplane. Vergence induced by optic flow motion was enhanced by disparity from motion. The results suggest that optic flow and disparity work together during fore/ aft motion to stabilize gaze. CR: Z. Tai, None; R.W. Hertle, None; E.S. Hald, None; D. Yang, None. Support: NIH EY015797,RPB,and CRMF of University of Pittsburgh 2891 - A76 Vergence Dynamics in Traumatic Brain Injury 2892 - A77 Accommodative Training to Reduce NITM and Improve Accommodative Accuracy in Asymptomatic Myopic Young-Adults D.G. Szymanowicz, P. Thiagarajan, W. Green, K.J. Ciuffreda, D. Ludlam. State College of Optometry, State University of New York, New York, NY. Purpose: Recent retrospective studies have found abnormalities of static clinical vergence parameters in traumatic brain injury (TBI) patients. The purpose of the present study was to investigate the first-order symmetric vergence dynamics in TBI. Methods: Non-strabismic TBI patients (n=10, mean age 30.2±5.01years) with near vision symptoms, and asymptomatic visually-normal (non-TBI) subjects (n=10, mean age 25.2±0.91years), were tested. Binocular horizontal position of the eyes was recorded objectively and continuously using the Power Refractor II, based on infra-red video photorefraction, with a sampling rate of 12.5Hz and resolution of < =0.5 degrees. The stimulus amplitude was 6.5º for both convergence and divergence. Targets comprised the red fixation LED located on the measuring head of the power refractor at 1m and a white LED placed at 0.3m, both aligned along the midline. Subjects altered bifixation between the targets every 3-4 seconds upon command for one minute. Three convergence and 3 divergence responses were obtained for analysis from the eye position traces for each subject. An exponential decay function was fit to the traces, and the response amplitudes and time constants of convergence and divergence were obtained. The peak velocities were derived from first-order differentiation of the exponential equation. The mean amplitude, time constant, and the peak velocity of the responses of the TBI and normal groups were compared. Results: Mean convergence response amplitude of the TBI group (6.4±0.3°) and the normal group (6.2±0.2°) was not significantly different (p=0.65). Similarly, mean divergence response amplitude of the TBI group (6.4±0.2°) and the normal group (6.5±0.2°) was not significantly different (p=0.77). However, there were significantly reduced (p<0.01) mean peak velocities and increased time constants for both convergence (15.5±0.94°/sec; 432.4±31ms) and divergence (15.6±0.96°/sec; 448.8±39.5ms) in the TBI group when compared to convergence (28.7±1.2°/sec; 221±9.6ms) and divergence (24.8±1.2°/sec; 273.4±19.1ms) in the visually-normal group, respectively. Conclusions: The TBI group demonstrated significantly slowed dynamic vergence responses. Since the neural control for vergence involves numerous motor and premotor areas, it appears that multiple axonal pathways are susceptible to diffuse axonal injury from the TBI, resulting in slowed vergence responsivity. More specifically, we speculate it may compromise the firing rate of vergence burst cells that are related to vergence velocity. However, the similar response amplitudes in both groups suggest unaffected activity of vergence tonic cells related to vergence angle. CR: D.G. Szymanowicz, None; P. Thiagarajan, None; W. Green, None; K.J. Ciuffreda, None; D. Ludlam, None. Support: None K.J. Ciuffreda, B. Vasudevan, D. Ludlam. Vision Sciences, SUNY College of Optometry, New York, NY. Purpose: To assess objectively changes in the NITM (nearwork-induced transient myopia) parameters of initial magnitude and its decay duration, as well as accuracy of the near accommodative steady-state response and clinically-based accommodative facility, following 6 weeks of home-based monocular and binocular accommodative vision training (i.e., oculomotor learning) in asymptomatic myopes. Methods: 10 young-adult myopes with a mean age of 23.6 (±2.2) participated. The experimental paradigm consisted of a baseline session and two follow-up sessions at the end of the 3rd and 6th weeks of training. At the first session, baseline refractive state and the selected static and dynamic accommodative functions were assessed objectively. Measurements were repeated at the two follow-up sessions. Conventional home-based vision training emphasizing dynamic aspects using step inputs included lens flippers (±2D) at near (40cm), Hart chart at distance (6m) and near (40cm), and prism flipper (6pd) training at near (40cm), all of which were performed for 20 minutes a day 5 days a week for 6 weeks (10hrs total). Thus, both blur and vergence-driven accommodation, and their interactions, were involved. Results: The dynamic accommodative response functions improved significantly with training, whereas the steady-state (static) response functions were only slightly improved. Dynamic: NITM decay duration decreased significantly with training from 101secs to 74secs. Lens flipper rate increased significantly from 11 to 16cpm in the OD, 11 to 19cpm in the OS, and 8 to 11cpm in the OU. Hart chart rate increased significantly from 22 to 33cpm in the OD. Static: Initial NITM magnitude decreased slightly from 0.53D to 0.47D, whereas the steady-state accommodative response increased slightly from 2.64D to 2.72D, following training. Conclusions: Training of the accommodative system resulted primarily in improved dynamics in both the laboratory and clinical measures. The results suggest the presence of rapid motor learning involving both the parasympathetic and sympathetic systems. Faster dynamics would result in decreased time-integrated retinal defocus, a potential myopigenic factor. In addition, the results suggest improved blur processing with training. CR: K.J. Ciuffreda, None; B. Vasudevan, None; D. Ludlam, None. Support: COVD Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 2889-2892 Tuesday, May 5, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 2873 - 2896 / A58 - A81 325. Eye Movements, Stereopsis and Visuomotor Organization Organizing Section: EY 2893 - A78 Nitm Following Marked Sustained Accommodation at Near 2894 - A79 The Effect of Induced Anisometropia on Accommodation and Vergence During Development M. Arunthavaraja, K.J. Ciuffreda, B. Vasudevan. State College of Optometry, State University of New York, New York, NY. T.R. Candy, S.R. Bharadwaj. Optometry, Indiana University, Bloomington, IN. Purpose: It has been speculated that NITM (accommodatively-based nearworkinduced transient myopia) is myopigenic in nature. Thus, the purpose of the present investigation was to determine objectively the initial magnitude of NITM, and its potential additivity, following successive but interrupted periods of marked, sustained accommodation at near in asymptomatic young adult myopic subjects. Methods: Fifteen visually normal, asymptomatic young adults (ages 18 - 28 years) were tested with full distance refractive correction. They included 9 early-onset (EOM) and 6 late-onset (LOM) myopic subjects. Accommodation was assessed objectively with a Canon R-1, open-field infrared auto-refractor under monocular viewing conditions (RE). The distance refractive state was measured immediately before and after each of the 3 ten minute periods of focusing upon a moderate contrast (50%), near target (12 cm; 8D) subtending 6 degrees. The task was repeated twice with a 5-minute inter-task rest period of imposed far viewing. NITM was defined as the post-task minus pre-task change in distance refractive state immediately following each task. Results: Significant amounts of NITM were generated following each trial. These ranged from 0.11 to 0.71D, with a mean of 0.31D. The group mean NITM was 0.32, 0.29, and 0.31D for trials 1, 2, and 3, respectively. For the EOMs subgroup, NITM was 0.28, 0.30, and 0.34D, while for the LOMs subgroup, it was 0.38, 0.29, and 0.26D, for for trials 1, 2, and 3, respectively. However, additivity of NITM was not found following the sequence of interrupted near tasks. Conclusions: There was no evidence of NITM additivity following a marked and sustained, but interrupted, near task. Although NITM has been reported to be additive following long periods of sustained reading (Vasudevan & Ciuffreda, 2008), providing rest periods between near task trials appears to prevent a cumulative effect. These findings support the idea of far viewing being protective in nature from myopia development. CR: M. Arunthavaraja, None; K.J. Ciuffreda, None; B. Vasudevan, None. Support: None Purpose: Anisometropia is associated with abnormal visual development but does not result in routine presentation for an eye examination as it has no obvious signs and symptoms. Little is known about its influence on visual function during infancy and the pre-school years. Here, we optically induce anisometropia in typically developing infants and children for brief periods of time to determine the effect on accommodation and vergence - two functions that help maintain clear and single vision. Methods: Accommodative and vergence responses were recorded simultaneously using a PowerRefractor (25Hz). Twenty subjects (3.7 months to 29.8 years) watched a high contrast cartoon movie (1/f amplitude spectrum) on an LCD screen that moved between 80cms (1.25D) and 33cms (3.0D) at 0.50D/s, with a stable period of 4s at each viewing distance. This protocol was performed under four viewing conditions: i) habitual binocular viewing, ii and iii) with a +2D or +4D lens over one eye (induced anisometropia conditions) and iv) with one eye occluded using an IR filter. Accommodative and vergence gains were calculated for the 1.75D or MA stimulus for each viewing condition. Results: Binocular accommodative gains (Mean +/- SEM: 0.99 +/- 0.08) were significantly different (p=0.001) from monocular accommodative gains (0.47 +/- 0.09) for all ages (main effect: p=0.55). Accommodative gains with 2D (0.77 +/- 0.08) and 4D (0.76 +/- 0.08) of induced anisometropia were not significantly different from each other (p=0.99) or the binocular (p= 0.27 & 0.26, respectively) and monocular (p=0.07 & 0.06, respectively) conditions. The vergence gains were also significantly different for binocular (0.91 +/- 0.04) and monocular conditions (0.30 +/- 0.05) (p<0.001). The vergence gains with 2D (0.85 +/- 0.04) and 4D (0.69 +/- 0.04) of anisometropia fell between the two values. Both were significantly different from monocular conditions (p<0.001), but only the 4D was significantly different from binocular conditions (p=0.01). Subject’s age only had a marginal effect on the vergence gain (main effect: p=0.04). Conclusion: Accommodative and vergence performance of the typically developing visual system deteriorates in the presence of transiently induced anisometropia. However, some binocular cues appear to remain with induced anisometropia of 2D and 4D, as indicated by the accommodative and vergence gains being somewhat higher than in monocular viewing. These results are consistent with the reduction in available disparity information for vergence and poorer retinal image quality for controlling accommodation. CR: T.R. Candy, None; S.R. Bharadwaj, None. Support: NIH Grant EY 014460 (TRC) Fight for Sight post-doctoral fellowship (SRB) 2895 - A80 Accommodative-Vergence and Vergence-Accommodation Cross-link Gains in Preschoolers 2896 - A81 Visuo-attentional Abilities in Healthy Children Compared to Children with Ophthalmologic Disorders D.F. Teel, S.R. Bharadwaj, T.R. Candy. Indiana University, Bloomington, IN. M. Vilayphonh1,2, C. Cavézian1, L. Laloum 3, L. Watier4, M. De Agostini4, S. Chokron1. 1 Laboratoire de Psychologie et de Neurocognition, CNRS, UMR 5105, Genoble, France; 2Service de neurologie, Fondation Ophtalmologique Rothschild, Paris, France; 3Service de médecine interne, Hôpital des Quinze-Vingts, Paris, France; 4 U780 ifr 69, INSERM, Villejuif, France. Purpose: Accommodation and vergence interact through neural cross-links such that accommodation can drive vergence (AC/A ratio) and vergence can drive accommodation (CA/C ratio) to provide clear and single vision. Inappropriate crosslink gains are believed to lead to binocular vision anomalies. While the two systems interact from early infancy, adult-like interactions between them may be inappropriate during development. Relative to adults, reduced head size and typically hyperopic refractive error result in reduced vergence demands and elevated accommodative demands during infancy and early childhood. This study aims to make the first within-subject measures of the gains of both response AC/A and response CA/C ratios in a group of 2-4 year olds to understand strategies used to overcome these dissimilar demands; an age at which accommodative esotropia commonly appears. Methods: Accommodation and vergence responses were measured in a group of 2-4 year olds (mean age=3.3 ± 0.5 years) and a group of adults (mean age=28.1 ± 5.4 years) using the PowerRefractor (25Hz). To measure the AC/A gain (MA/D), subjects watched a high contrast cartoon movie (1/f amplitude spectrum) monocularly (open-loop disparity driven vergence) while accommodation was stimulated using a -2D lens. To measure the CA/C gain (D/MA), subjects watched a blurred version of the same movie (filtered using a <0.2 cpd difference-of-gaussian) binocularly (open-loop blur driven accommodation) while their vergence was stimulated using a 2MA prism. Results: Response AC/A ratios were significantly higher (p=0.01) in adults (Mean + SD: 0.90 ± 0.15 MA/D) than in children (0.58 ± 0.21 MA/D) while the response CA/C ratios of adults (0.36 ± 0.2 D/MA) and preschoolers (0.45 ± 0.15 D/MA) were not significantly different (p=0.335). Conclusions: The response AC/A ratio (in MA/D) would be higher in 2-4 year olds than in adults if the angular rotation of the eyes generated by the accommodativevergence cross-link remained constant with age. Conversely, the response CA/C ratio (in D/MA) would be lower than in adults if the dioptric change in focus generated by the vergence-accommodation cross-link remained constant with age. These results do not follow these predictions, indicating a recalibration of both cross-link gains with age. CR: D.F. Teel, None; S.R. Bharadwaj, None; T.R. Candy, None. Support: NEI Grant EY014460(TRC) NEI K12 Grant EY15504(DFWT) Purpose: Previous studies suggest that peripheral visual alteration could modify visual cognition. One can assume that an early decrease in visual acuity (i.e., related to peripheral damage in childhood) could lead to visuospatial cognitive disorders. Moreover, it has been shown that these cognitive impairments could underlie specific learning disabilities such as difficulties in written language. The goal of the current study was to explore visuo-attentional skills (e.g., visual scanning strategies, visual memory and visual processing) in children with ophthalmologic disorders. Methods: 106 right-handed children (28 patients; 78 healthy controls), aged from 4 to 8, with normal or corrected-to-normal vision, performed six visuospatial tasks, including three cancellation tasks (Teddy Bear, Bell, and the Corkum tests), visuospatial working memory tasks (Borel-Maisonny symbol orientation task, shape and letter matching tasks), and a visual discrimination task (the Embedded Figures Test). The patients were diagnosed with either a simple strabismus or a strabismus associated with another ophthalmologic disorder. Results: Healthy controls performed better than patients in the Teddy bear, Triangle, T2 Corkum cancellation task, Embedded Figures Test. Age played an important role for the Triangle, T2 Corkum, Embedded Figures Test, and symbol orientation tasks where the oldest group showed better results than the youngest children. Conclusions: This study gives information regarding visuo-attentional development in a large sample of healthy children. Our results highlight that visuo-attentional abilities are not optimal at 4 years old but indeed improve at least until 8 years. Yet, in ophthalmologic children, despite having corrected-to-normal vision, a long-lasting impaired visuo-attentional skill is observed. These findings suggest that attention and spatial skills training could be proposed in young children with corrected vision before formal reading education. CR: M. Vilayphonh, None; C. Cavézian, None; L. Laloum, None; L. Watier, None; M. De Agostini, None; S. Chokron, None. Support: B and E Rothschild Fondation Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 2893-2896 Tuesday, May 5, 1:45 PM - 3:30 PM Palm A Paper Session Program Number Range: 3037 - 3043 343. Extraocular Muscles and Nystagmus Organizing Section: EY 3037 - 1:45PM Retinoic Acid Regulates Orbital Development and Extraocular Muscle Organization in Zebrafish 3038 - 2:00PM Nerve-Muscle Interplay in the EOMs: Effects of Progressive Denervation on Human and Transgenic Mice With Amyotrophic Lateral Sclerosis (ALS) A. Kahana1, F. Elsaeidi1, D. Demiri1, B.L. Bohnsack1, A.-A. Calinescu1, D. Goldman2. 1 Kellogg Eye Center, Univ of Michigan, Ann Arbor, MI; 2Biochemistry, Molecular and Behavioral Neuroscience Institute, Univ of Michigan, Ann Arbor, MI. F. Pedrosa Domellof 1A, T. Brännström1B, P. Andersen1C, S. Marklund1D, J.-X. Liu1E. A Clinical Sciences/Ophthalmology, BMedical Biosciences, Division of Pathology, C Clinical Neurosciences, DMedical Biosciences, Division of Clinical Chemistry, E Integrative Medical Biology, Anatomy, 1Umea University, Umea, Sweden. Purpose: Orbital disease can involve reactivation of embryogenic pathways. We aim to utilize a novel zebrafish model of orbital development to evaluate the role of the neural crest in orbital organization. Methods: Zebrafish transgenic strains were used for real-time fluorescence and confocal microscopy to assess orbital development following experimental perturbations to the retinoic acid signaling system, including inhibition of RA synthesis with DEAB. In situ hybridization and immunohistochemistry experiments were used to complement the live microscopy experiments and identify potential targets. Results: Retinoic acid (RA) is a key morphogen during embryogenesis and a powerful teratogen, and its synthesis is tightly regulated both spatially and temporally. RA is also a key regulator of neural crest development. Evidence from mouse molecular genetics revealed a key role for RA signaling in the regulation of orbital development, although the exact mechanism and key intercellular interactions remain to be discovered. We developed a zebrafish model for studying orbital development utilizing transgenic strains for realtime assessment of extraocular muscles (EOM) and cranial neural crest development, along with ISH and IHC experiments. Using this model, we inhibit retinoic acid synthesis with DEAB beginning at 24hpf and show that EOM differentiate appropriate, but the exact anatomic localization of EOMs around the eye is disrupted (figure). Conclusions: Zebrafish orbital development reveals a dependence on RA signaling that is very similar to data from existing mammalian models. The zebrafish model allows us to further characterize the key cellular interactions and signaling pathways using live microscopy techniques where cellular microenvironments around the eye can be observed intact. This is a powerful model that has great promise to further our understanding of orbital and extraocular muscle development and disease. CR: A. Kahana, None; F. Elsaeidi, None; D. Demiri, None; B.L. Bohnsack, None; A.-A. Calinescu, None; D. Goldman, None. Support: NIH Grants K08EY018689 to AK; 5R01EY018132 to DG; 5P30EY007003 to the Kellogg Eye Center; and 5P30CA46592 to the University of Michigan’s Cancer Center. 3039 - 2:15PM The Effect of Recession Surgery on Rabbit Extraocular Muscle Myosin Expression and Satellite Cell Activity R.S. Antunes-Foschini1, B. Limmer2A, S.P. Christiansen2A, L.K. McLoon2B. 1 Ophthalmology, HC- FMRP - University of Sao Paulo, Ribeirao Preto, Brazil; A Ophthalmology and Pediatrics, BOphthalmology and Neuroscience, 2University of Minnesota, Minneapolis, MN. Purpose: Surgical recession of extraocular muscles (EOM) is a common treatment for strabismus and other motility disorders. Recession involves the removal of the muscle from its scleral insertion and reattaching the muscle at a point posterior to the original site of insertion. The purpose is to reduce the force of an overacting muscle and restore normal eye position. We examined the effect of this procedure on the activity of satellite cells and myosin heavy chain isoform expression in the recessed extraocular muscle of adult rabbits compared to normal control muscles. Methods: The insertion of the superior rectus (SR) muscle was detached from the sclera and sutured 7 mm posterior to its original insertion site. After 7 days the animals were injected every 2 hours for 12 hours with bromodeoxyuridine (brdU), followed by a 24 hour brdU-free period. The superior rectus muscles were examined for brdU incorporation and neonatal and developmental myosin heavy chain (MyHC) isoform expression changes in the mid-region and tendon ends of the muscles and compared to control superior rectus muscles. Results: In the recessed muscle, the percentage of brdU positive satellite cells in the orbital layers was increased compared to normal control SR muscles, and particularly elevated in the tendon region of the treated muscle. The global layer showed little alteration in satellite cell rates of division, with only a small increase in the tendon end of the global layer. In the global layer of both the middle and tendon ends of the recessed muscles, neonatal and developmental MyHC expression was significantly decreased. Conclusions: Surgical recession of the superior rectus muscle resulted in an increase in satellite cell division at 7 days post-surgery. In contrast to surgical resection, recession surgery resulted in a marked decrease in expression of the immature myosin heavy chain isoforms. This demonstrates that the muscles respond to the reduction in length by remodeling both their myosins and satellite cell activity. It may be possible to improve the post-surgical effects of recession surgery by modulating these processes. CR: R.S. Antunes-Foschini, None; B. Limmer, None; S.P. Christiansen, None; L.K. McLoon, None. Support: Fapesp 2007/05260-0, NIH EY15313 and EY11375 Purpose: To explore extent and consequences of progressive denervation in the EOMs of ALS patients and of transgenic ALS mouse models. Methods: EOM samples obtained at autopsy from 7 ALS patients and from 4 elderly controls (72-86 y), 7 adult controls (26-56 y), as well as from transgenic mice with SOD1 mutations (D90A, G93A, G85R) paralleling familiar ALS, were processed for immunocytochemistry with antibodies against Schwann cell markers (S-100, p75, GFAP), gangliosides GD1b and GQ1b/GT1a, parvalbulmin, myosin heavy chains and laminin chains. Neuromuscular junctions (NMJs) were identified with alphabungarotoxin and acetylcholinesterase. Results: Differences in the expression of gangliosides GD1b and GQ1b/GT1a and Schwann cell marker S-100 at the NMJs and nerves were noted in the human EOMs of ALS patients compared to those of the elderly controls. Parvalbumin was absent or scarce in EOM nerve trunks of ALS patients, with few exceptions. Changes in the composition of the extracellular matrix observed in EOMs of human familial ALS with D90A mutation were also present in the corresponding transgenic mouse. Further characterization of the EOMs in the transgenic mice is ongoing. Conclusions: There are signs of denervation of the human EOMs in late stages of ALS although these muscles appear selectively spared at the muscle fiber level. The presence of high levels of parvalbumin have been proposed to be protective for oculomotor neurons in ALS but in advanced stages of the disease this difference in calcium-binding proteins is no longer apparent in most cases. The identification of similar endpoints in the EOMs of patients with D90A mutation and the ALS transgenic mice carrying the same mutation indicates that this is a useful model to study the temporal aspects of progressive denervation in the EOMs and to explore aspects of muscle-nerve interplay that protect the EOMs in motoneuron disease. Finally knowledge on the effects of denervation may give us insights on the spatial organisation of motor units and fascicle organisation in the EOMs. CR: F. Pedrosa Domellof, None; T. Brännström, None; P. Andersen, None; S. Marklund, None; J.-X. Liu, None. Support: Swedish Research Council (63x-20399), Synfrämjandets Forskningsfond, Stiftelsen Kronprinsessan Margaretas Arbetsnämnd för Synskadade KMA 3040 - 2:30PM A Comparison of Clinical and Eye Movement Characteristics Between Albinism and Idiopathic Infantile Nystagmus With and Without Mutations in the FRMD7 Gene A.A. Kumar, F.A. Proudlock, S. Thomas, I. Gottlob. Ophthalmology, University of Leicester, Leicester, United Kingdom. Purpose: No differences between nystagmus associated with albinism and idiopathic infantile nystagmus (IIN) have been described. Recently mutations in a novel gene called FRMD7 have been found which allow definitive identification of a homogenous group of idiopathic nystagmus patients. We have compared clinical and eye movement characteristics between albinism and IIN with and without mutations in the FMRD7 gene Methods: Visual acuities and eye movements (infrared pupil tracker) were recorded from 50 albino subjects, 83 subjects with the FRMD7 mutation and 45 subjects without the FRMD7 mutation Results: Mean visual was significantly worse in albinos compared to IIN patients (p<<0.0001). Although there was no significant differences between the groups (p>0.05) for nystagmus amplitude, the frequency of nystagmus was significantly slower in albinism (p<<0.0001). In addition, nystagmus associated with albinism was significantly more likely to be jerk nystagmus rather than pendular nystagmus compared to FRMD7 group (p<<0.0001). The most common waveform associated with albinism was pure jerk nystagmus, whereas non-FRMD7 was more likely to be associated with jerk with extended foveation Conclusions: Contrary to available literature, nystagmus associated with albinism shows distinct differences to IIN both with and without FRMD7 mutations. This suggests the possibility of different underlying mechanisms to albinism and IIN in generating eye oscillations although these are yet to be elucidated CR: A.A. Kumar, None; F.A. Proudlock, None; S. Thomas, None; I. Gottlob, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 3037-3040 Tuesday, May 5, 1:45 PM - 3:30 PM Palm A Paper Session Program Number Range: 3037 - 3043 343. Extraocular Muscles and Nystagmus Organizing Section: EY 3041 - 2:45PM Foveation and Acuity Deficits in Patients With Idiopathic Infantile Nystagmus Syndrome Across a Wide Age Range 3042 - 3:00PM Spectral Domain Optical Coherence Tomography in the Oculocutaneous Albino Population J. Felius1,2, D.R. Stager, Sr. 2, C.H. Vu1. 1Retina Foundation of the Southwest, Dallas, TX; 2Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX. T.H. Cronin1, R.W. Hertle1, H. Ishikawa1,2, J.S. Schuman1,2. 1UPMC Eye Center, Eye and Ear Institute, University of Pittsburgh School of Medicine, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, Pittsburgh, PA; 2 Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA. Purpose: Previously we introduced the Nystagmus Optimal Foveation Function (NOFF) (Felius et al, 2008 ARVO) as an objective ocular motor outcome measure for infants and young children in whom determining the Expanded Nystagmus Acuity Function (NAFX) may not be feasible. The NAFX (Dell’Osso et al, 2002 Doc Ophthalmol) is an established measure of foveation, predictive of visual acuity in patients with idiopathic infantile nystagmus syndrome (IINS). Both NAFX and NOFF are based on simultaneous position and velocity criteria that define ‘foveation’, but the NOFF allows for within-session positional changes. Here we validate the NOFF against the NAFX in older patients and study the relationship with visual acuity in IINS from infancy to adulthood. Methods: Calibrated horizontal eye movement data from 20 patients with IINS (age 6-27 years) were analyzed using both NOFF and NAFX algorithms, and the results compared to binocular visual acuity from the same visit. The NOFF and age-corrected visual acuity data were combined with data from 32 infants and young children (age 5 months-6 years) with IINS. Results: In the 6-27 year age group, the NOFF (mean±SD=-1.5±1.7 logits) correlated with the NAFX (0.43±0.24 logMAR) (r2=0.94; P<0.001). The acuity values predicted by the NAFX algorithm correlated with measured visual acuity (0.36±0.25 logMAR) (r2=0.37; P=0.004). For the combined group of 52 patients, age-corrected visual acuity was associated with the NOFF and fit by a exponential model as previously described, explaining 35% of the variance (P<0.001). Conclusions: The excellent correlation with the NAFX in older children and adults validates the NOFF as a measure of foveation. The strong relationship between NOFF and visual acuity in IINS explained a similar amount of variance as in the relationship between NAFX and visual acuity in older patients. These results confirm the association between foveation statistics and binocular visual acuity in IINS and extend it to a very young age range. The finding that only 1/3 of the variance in visual acuity is explained by either NOFF or NAFX may be due to noise, the somewhat limited range of this cohort, and/or it may indicate that factors other than foveation statistics play a role. CR: J. Felius, None; D.R. Stager, Sr., None; C.H. Vu, None. Support: Vision of Children Foundation Purpose: To evaluate the clinical utility of spectral domain optical coherence tomography (SDOCT) on macular imaging in eyes with oculocutaneous albinism (OCA) and to investigate the afferent and efferent system in this unique subset of nystagmus patients using SD-OCT. Methods: Three-dimensional macular cube scans (200x200x1024 samplings in a 6x6 mm region centered on fovea) were obtained 3 times on each eye of 9 OCA patients. The central macular thickness and horizontal eye movement frequency were recorded. The average horizontal eye movement frequency was compared to that obtained from eye movement recordings. Results: The age range of the 9 patients was 7-58 years (average 18 years). All patients had infantile nystagmus syndrome (INS) with 6 patients (67%) displaying aperiodicity. Macular images were successfully obtained in 8 patients (89%). Seven patients (88%) demonstrated “fovea plana” and one patient demonstrated a slight foveal depression. In agreement with prior studies, central macular thickness was found to be increased in the OCA population (284µm ± 56µm) compared to the general population. Eye movement frequency on SD-OCT (range 2-4 Hz, average 3.5 ± 0.8 Hz) was calculated and agreed with that of eye movement recordings (range 2-5 Hz, average 3.6 ± 0.6 Hz, paired student t-test, 95% CI [-0.7,0.5], p = 0.78). Conclusions: SD-OCT provides detailed structural imaging of the sensory system of OCA despite perpetual eye movement during scanning, revealing a major structural anomaly in the macula. In addition, SD-OCT offers an alternative method of studying the motor physiology of ocular oscillation in OCA. Figure 1. Frame from SD-OCT movie demonstrating fovea plana in oculocutaneous albino eye with infantile nystagmus syndrome at 3-5 Hz frequency. Figure 2. SD-OCT image of y-plane demonstrating horizontal nystagmus eye movements at 3-5 Hz frequency. CR: T.H. Cronin, None; R.W. Hertle, None; H. Ishikawa, Bioptigen, P; J.S. Schuman, Carl Zeiss Meditec, P; Bioptigen, P; Alcon, R; Allergan, R; Carl Zeiss Meditec, R; Heidelberg Engineering, R; Merck, R; Lumenis, R; Optovue, R; Pfizer, R. Support: NIH R01-EY013178-9, P30-EY008098; Eye and Ear Foundation (Pittsburgh, PA); Research to Prevent Blindness 3043 - 3:15PM Neural Circuit involved in Idiopathic Nystagmus Syndrome Based on fMRI L.E. Leguire, IV1A,2A, N.H. Kashou1B, N. Fogt2B, M. Smith1B, J.R. Lewis2A,2C, R. Kulwin1B, G. Rogers1A,2A. AOphthalmology, BRadiology, 1Nationwide Children’s Hospital, Columbus, OH; AOphthalmology, BCollege of Optometry, CBiomedical Engineering, 2 Ohio State University, Columbus, OH. Purpose: Idiopathic Nystagmus Syndrome (INS) is characterized by early onset alternating series of slow and rapid eye movements which can manifest in different waveforms and genetic lines. The neural circuitry of INS is not known. Methods: A novel fMRI method was utilized to identify the neural circuitry for INS in humans by use of a GE 3T MRI scanner utilizing FEAT-FSL and FILM time series analysis with a cluster significance threshold of P=.01. The null point, a gaze position with minimal nystagmus, was utilized as the “off” condition and a gaze position with robust nystagmus was utilized as the “on” condition. Standard on-off fMRI sequence was employed whereby a fixation point alternated between the null and robust nystagmus positions. Eye movements were recorded with an fMRI compatible eye tracker (ASL) and observed in real time to ensure subject compliance and to quantify oculomotor function in “on” and “off” states. INS subjects (N= 4) included three family members (mother and two daughters) with autosomal dominant INS as well as age and gender matched normal controls (N=3). Results: Three of four INS subjects demonstrated significant increased activation of the Declive of the Cerebellum while no normal subjects, under identical conditions, showed activation of the Declive. Both groups showed significant activation in the occipital lobe (Brodmann Areas 17, 18, 19, Cuneus). Conclusions: A novel fMRI method demonstrated that the Declive of the Cerebellum is actively involved in INS. These are the first results to identify the Cerebellum, and specifically the Declive, as a possible site for the oculomotor dysfunction associated with INS. CR: L.E. Leguire, IV, None; N.H. Kashou, None; N. Fogt, None; M. Smith, None; J.R. Lewis, None; R. Kulwin, None; G. Rogers, None. Support: Ohio LIONS Eye Research Foundation, Fight for Sight, Inc (GA03023) Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 3041-3043 Tuesday, May 5, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 3189 - 3200 / D718 - D729 356. Optic Nerve Injury and Regeneration Organizing Section: EY Contributing Section: RE 3189 - D718 In Vitro Characterization of Novel Neuroprotective Phosphine-Borane Complexes 3190 - D719 Identification of Protein Targets of Novel Neuroprotective Sulfhydryl Reducing Drugs N.J. Niemuth1, C.J. Lieven1, L.A. Levin1,2. 1Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI; 2Ophthalmology, University of Montreal, Montreal, QC, Canada. A.L. Kloosterboer1, J.R. Ribich1, L.A. Levin1,2. 1Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, WI; 2Ophthalmology, University of Montreal, Montreal, QC, Canada. Purpose: Phosphine-borane (PB) complexes bis (3-propionic acid methyl ester) phenylphosphine borane complex (PB1) and (3-propionic acid methyl ester) diphenylphosphine borane complex (PB2) are novel neuroprotective compounds. We previously demonstrated that they have a positive, dose-dependent effect on the viability of RGCs after axonal injury (Schlieve et al., Exp Eye Res 83:1252, 2006), which we hypothesize results from their ability to chemically reduce critical disulfides formed as a result of oxidation by reactive oxygen species. We performed in vitro testing of the effectiveness of these complexes and their utility as drugs, focusing on their reducing power, solubility, blood-brain barrier permeability, and accelerated stability. Methods: Relative reducing power was tested using Ellman’s reagent (DTNB), which turns yellow when its disulfide linkage is reduced. Reaction of various concentrations of dithiothreitol, tris (carboxyethyl) phosphine, PB1, or PB2 with 30 mM DTNB in methanol was carried out in buffer at pH 5, 7, and 9. Octanol/water partitioning was carried out on PB1 and PB2 to determine their solubility in aqueous solution. A modified PAMPA assay was used to determine blood-brain barrier permeability of PB1. An artificial membrane was created on a filter plate using porcine polar brain lipids dissolved in hexanes. PB1 in PBS was placed in the donor well above the membrane, and PBS placed in the acceptor well below the membrane. Concentration of PB1 in each well after 18 hours was calculated by comparison to a standard curve of PB1 in PBS. Accelerated stability was determined by incubating 4 mg of pure PB1 and PB2 in sand baths at 40°C and 60°C for 37 days, followed by HPLC. Results: There was a linear relation between concentration and reducing power for each compound. PB1 and PB2 had maximal reducing capability at pH 7. log Poct/wat for PB1 was 0.65 (somewhat soluble) and for PB2 was 1.1 (minimally soluble). log Pe for PB1 was -5.86 (Pe = 1.38x10 -6), a low BBB permeability similar to that of caffeine and aldosterone. Peak areas for PB1 at 40°C and 60°C were 80% and 72% of control respectively at 37 days. PB2 peak areas were 100% of control for both conditions at 37 days. Conclusions: Both PB complexes are effective reducers of disulfides. PB2, while highly lipophilic, is more stable than its water-soluble counterpart. CR: N.J. Niemuth, None; C.J. Lieven, None; L.A. Levin, Assigned to Wisconsin Alumni Research Foundation, P. Support: NIH R21EY017970, P30EY016665 and an unrestricted departmental grant from Research to Prevent Blindness, Inc. Purpose: Previous work in our laboratory has shown elevated intracellular superoxide is a critical event in the death of retinal ganglion cells (RGCs) after axotomy. The sulfhydryl-reducing compounds tris(2-carboxyethyl) phosphine (TCEP) and bis(3propionic acid methyl ester) phenylphosphine borane complex (PB1) rescue RGCs from apoptosis. We used a novel two-dimensional gel electophoresis method to detect changes in oxidation state of protein sulfyhydryls after treatment with PB1 in a transformed retinal ganglion cell-like cell line (RGC-5). Methods: Cultured RGC-5 cells were treated with 10 μM PB1 for 8 hours following which cellular and mitochondrial proteins were separated on a 4-20% polyacrylamide gradient gel. The lane was excised, reduced with 25 mM dithiothreitol, rinsed, and alkylated with 100 mM iodoacetamide. The excised slice was placed horizontally on a second gel, electrophoresed into the second dimension, and stained with Pierce® color silver stain or Sypro® Ruby. Results: Several proteins were found in consistent locations below the diagonal when prepared from control cells, but not cells treated with PB1, indicating that they contained disulfides that were reduced by PB1. Conclusions: A relatively small number of cellular and mitochondrial proteins are targets for the novel reducing agent PB1, and one or more may be critical for its activity as a neuroprotective agent. CR: A.L. Kloosterboer, None; J.R. Ribich, None; L.A. Levin, Wisconsin Alumni Research Foundation, P. Support: NIH R21EY017970 and P30EY016665 and an unrestricted departmental grant from Research to Prevent Blindness, Inc. 3191 - D720 Neurotrophic Effect of a Novel TrkB Agonist on Retinal Ganglion Cells 3192 - D721 Sequence of Apoptosis Signaling Induced by Serum Deprivation in Differentiated RGC-5 Cells Y. Hu1, S. Cho2, J.L. Goldberg1. 1Bascom Palmer Eye Institute, University of Miami Miller School of Med, Miami, FL; 2Neuroscience Discovery Research, Wyeth Research, Princeton, NJ. Purpose: Retinal ganglion cells (RGCs) die in glaucoma and a number of other optic neuropathies. Recently, novel TrkB monoclonal antibodies have been shown to be able to activate TrkB receptors and exert neuroprotective and neurotrophic effects (Qian et al., 2006). In previous study, we examined the ability of one of these, 29D7, on RGC survival in culture. In the present study, we examined the ability of 29D7 on RGC survival and neurite growth both in culture and in vivo. Methods: RGCs from postnatal day (P)3-4 Sprague-Dawley rats were isolated to over 99% homogeneity by sequential immunopanning using a monoclonal antibody to Thy1. RGCs were cultured in 96 well plates pre-coated with poly-D-lysine and laminin at a density of 2x103 cells/well, in serum-free defined medium. RGC viability was assessed after 1-3 days by an MTT assay. The activation of TrkB downstream signals was confirmed by immunofluorescence and Western blot. Intravitreal injections of 29D7 were performed after ON axotomy, RGC survival was quantified using ß-III tubulin immunostaining. Regeneration was assessed using retrograde flurogold (FG) tracing in ON-peripheral nerve (PN) graft model. Results: Similar to brain-derived neurotrophic factor (BDNF), the 29D7 antibody strongly promoted RGC survival and neurite growth in vitro compared with medium alone or control IgG at 24 hours in culture. Forskolin, which weakly supported RGC survival on its own, potentiated the effect of 29D7. Intravitreal injection of 29D7 enhanced RGC survival but not regeneration in vivo 2 weeks after injury. Conclusion: These findings demonstrate the potential for antibody-mediated TrkB agonism as a potential therapeutic reagent to enhance RGC survival after injury or in degenerative disease. Further studies are needed to elucidate the mechanistic differences between TrkB agonist and BDNF. CR: Y. Hu, None; S. Cho, Wyeth conflict of interest, I; J.L. Goldberg, None. Support: NEI R21 EY017971 (JLG), The Glaucoma Foundation (JLG), NEI P30 EY014801 (UM), and an unrestricted grant from Research to Prevent Blindness C.J. Lieven1, K.M. Thurber1, E.J. Levin1, L.A. Levin1,2. 1Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, WI; 2Ophthalmology, University of Montreal, Montreal, QC. Purpose: Serum deprivation induces apoptosis in many cell types, but can be prevented by drugs that scavenge or inactivate reactive oxygen species, implicating the latter in apoptosis signaling. Previous work in our laboratory showed that superoxide was an intracellular signal for cell death in primary retinal ganglion cells after axotomy, a condition causing both axonal injury and deprivation of tectum-derived growth factors. We studied superoxide signaling of serum deprivation-induced apoptosis in a transformed retinal ganglion cell line (RGC-5), in order to elucidate whether it was acting as an upstream or downstream signal. Methods: We correlated superoxide levels with the time course of cytochrome c release after serum deprivation. RGC-5 cells were cultured for 24 hrs and differentiated to a neuronal phenotype with staurosporine. Four hours after differentiation, cells were either left undisturbed, switched to a serum-free medium, or treated with etoposide, a known inducer of apoptosis. Untreated and etoposide-treated cells were stained with hydroethidium and fixed after 1 and 24 hours in culture. Serum-deprived and untreated cells were similarly stained and fixed at 24 and 72 hrs post-treatment. Cytochrome c was localized by immunofluorescence. Cells were photographed for quantitative and qualitative analysis. Tests for significance were with Student’s t or chi-square. Results: Serum deprivation led to a significant increase in superoxide levels in differentiated RGC-5 cells compared to control cells at 72 hrs (1.73 ± 0.14 vs 1.00 ± 0.02; p<0.001). Analysis of cytochrome c localization along with superoxide levels showed that the rise in superoxide preceded the release of cytochrome c from the mitochondrion. Superoxide levels return to basal levels after cytochrome c release, indicating superoxide’s role as an upstream signaling molecule in the apoptotic cascade. Conclusions: Superoxide production in serum-deprived RGC-5 cells is an early signal in triggering apoptosis. Work is being performed in our laboratory now to determine the sites of action of superoxide, and ways of preventing or reversing its effects before caspase activation can occur and cells become committed to an apoptotic fate. CR: C.J. Lieven, None; K.M. Thurber, None; E.J. Levin, None; L.A. Levin, US 7,303,915, P. Support: NIH R21EY017970, P30EY016665 and an unrestricted departmental grant from Research to Prevent Blindness, Inc. Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 3189-3192 Tuesday, May 5, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 3189 - 3200 / D718 - D729 356. Optic Nerve Injury and Regeneration Organizing Section: EY Contributing Section: RE 3193 - D722 Qualitative and Quantitative Analysis of Brn3a Expression in Naïve, Optic Nerve Transected and Optic Nerve Crushed Adult Rat Retinas 3194 - D723 The Involvement of p53, p63 and p73 in Retinal Ganglion Cell Death After Axonal, Ischemic and Elevated Intraocular Pressure Injury F. Nadal-Nicolas, M. Jimenez-Lopez, P. Sobrado-Calvo, L. Nieto-Lopez, I. CanovasMartinez, M. Salinas-Navarro, M. Vidal-Sanz, M. Agudo. Ophthalmology, University of Murcia, Murcia, Spain. E.M. Jokinen1A,1B, O. Renko1A,1B, K. Tuppurainen1B, U. Lönngren2, N. Turunen1A,1B, M. Lafuente3, M. Vidal-Sanz3, F. Hallböök 2, U. Napankangas1A,1B. ADepartment of Ophthalmology, BDepartment of Pathology, 1Oulu University, Oulu, Finland; 2 Department of Developmental Neuroscience, Uppsala University, Uppsala, Sweden; 3Department of Ophthalmology, University of Murcia, Murcia, Spain. Purpose: To characterize Brn3a expression in adult albino rat retina and to quantify the population of RGCs expressing Brn3a in naïve as well as its temporal loss induced by intraorbital optic nerve transection (IONT) or crush (IONC). Methods: Brn3a expression was characterized using morphometric methods. RGCs were doubly labelled with the regrotrade neuronal tracer Fluorogold applied to both superior colliculi (SCi), and with antibodies to POU-domain protein Brn3a. Eyes were extracted at increasing survival intervals (2, 5, 9, or 14 days) after axotomy, and the retinas were analyzed to determine the population of RGCs positive for Brn3a and FG. Results: Brn3a expression was limited to the ganglion cell layer. The percentage of RGCs positive for FG and Brn3a in naïve retinas was 92,2%. Quantification of the whole RGC population showed that in naïve retinas there were a mean of 80,251±2210 RGCs-FG+ and 83,449±4541 RGCs-Brn3a+ per retina (mean ±SD; n=14). The temporal course of RGC-Brn3a+ and RGCs-FG+ loss induced by IONC or IONT followed a similar trend, however the loss of RGCs-Brn3a+ was significant earlier than the loss of FG-labelled RGCs. Conclusions: The great majority of the RGCs-FG+ were also Brn3a+, thus Brn3a can be used as a reliable and efficient immunocytochemical marker for RGCs in control and optic nerve injured adult rat retinas. Axotomy induced RGC loss was detected earlier with Brn3a than with FG. CR: F. Nadal-Nicolas, None; M. Jimenez-Lopez, None; P. Sobrado-Calvo, None; L. Nieto-Lopez, None; I. Canovas-Martinez, None; M. Salinas-Navarro, None; M. Vidal-Sanz, None; M. Agudo, None. Support: ISCII: CP003/00119, ISCIII PI070225, ISCIII RD07/0062/0001, Fundación Séneca: 04446/GERM/07 and MECSAF-2005-04812. Purpose: p53, p63 and p73 are members of the p53 gene family involved in development, differentiation and cell response to stress. This study was undertaken to determine their possible involvement in retinal ganglion cell death after experimental injury. We studied the expression of p53, p63 and p73 mRNA in normal adult rat retina after optic nerve transection (ONT), selective ligature of ophthalmic vessels (SLOV) and acute increase in intraocular pressure (IIOP). Methods: Tissue samples of rat retina were collected 3, 7 and 14 days after ONT and IIOP, and 24h, 7 and 14 days after SLOV. Total RNA was extracted using Trizol, and cDNA was synthesized. The expression of target genes was evaluated with quantitative real-time PCR with SYBR Green assay. Normal, untreated rat retina samples were used as controls and the relative mRNA expression levels were calculated. Results: p53, p63 and p73 mRNA was detected in normal adult rat retina. After ONT the relative level of p53 was increased 1.5-fold at day 7 and p63 mRNA at day 3. p73 mRNA level was increased in all time points, 2-fold at days 3 and 7 and 1.5-fold at day 14. After SLOV the relative level of p53 mRNA showed 2.5-fold increase at 3 and 7 d and returned to normal by day 14. p63 expression increased 1.5-fold at day 3 and returned back to normal by day 7. p73 mRNA expression was increased at all time points. IIOP caused a transient decrease in p53 mRNA level at 24h whereas the relative level of both p63 and p73 mRNA was found to increase after IIOP. Conclusions: p63 and p73 expression can be detected from normal adult rat retina. The alterations in the relative mRNA levels of p53, p63 and p73 suggest that these genes are involved in retinal ganglion cell death after ONT, SLOV and IIOP. CR: E.M. Jokinen, None; O. Renko, None; K. Tuppurainen, None; U. Lönngren, None; N. Turunen, None; M. Lafuente, None; M. Vidal-Sanz, None; F. Hallböök, None; U. Napankangas, None. Support: Eye Foundation, Nissi Foundation, Finnish Medical Foundation 3195 - D724 Expression of Matrix Metalloproteinase-7 in Murine Optic Nerve Following Transection Injury 3196 - D725 Analysis of Cellular and Molecular Associated With Optic Nerve Degeneration and Regeneration j. shi, C.-W. Wu, S. Jain, J.-H. Chang, D.T. Azar. Department of Ophthalmology and Visual Sciences, The university of illinois at Chicago, Chicago, IL. A.S. Solomon1, S. Rosenzweig2A, A. Nitzan1, A. Barzilai2B. 1Goldschleger Eye Research, Tel-Aviv University, Tel-Hashomer, Israel; ANeurobiochemistry, BNeurobiology, 2 Tel-Aviv University, Faculty of Life Science, Israel. Purpose: To determine the expression of matrix metalloproteinases (MMPs) following murine optic nerve injury. Methods: Meningeal sparing optic nerve transection were performed in WT mice. Mice were sacrificed at week one and two, optic nerves were sectioned and confocal immolocalization was performed for MMP-2, -3, -7 and -14, myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP). Optic nerve regeneration was examined in wild type and MMP-7 knock-out mice using DiI tracing. Results: Immunostaining revealed that MMP-2, MMP-3, and MMP-14 were localized in the meningeal layers of mouse optic nerve, while MMP-7 was localized within the optic nerve. MMP-7 expression was increased following optic nerve injury. Double labeling indicated that MMP-7 is not expressed in oligodendrocytes, but may be expressed in astrocytes. DiI tracing revealed regeneration of some retinal ganglion cell axons. Conclusions: MMP-7 expression is increased after optic nerve transection suggesting a role for MMPs in scar formation and/or axonal regeneration following optic nerve injury. CR: J. shi, None; C.-W. Wu, None; S. Jain, None; J.-H. Chang, None; D.T. Azar, None. Support: Research to Prevent Blindness (RPB) Purpose: To elucidate the regenerative potential of injured optic nerve (ON). We present the results of a study on the regenerative potential of central nervous system (CNS) mammalian axons using our unique rat optic nerve model. We analyzed the cellular and molecular events that control the degenerative and regenerative processes in lower vertebrates such as goldfish, and mammals, following trauma to optic nerve. Material and methods: The right optic nerve of adult rats was completely transected while sparing the vasculature and the meninges. Hyaluronic acid (HA)-based hydro gel containing supportive factors or self-assembling peptides (SAP) were implanted in the gap generated by the surgery. Surgery and follow-up were performed according to the ARVO Rules for Treatment and Care of Animals. Two weeks and one month following the surgical procedure the animals underwent MRI evaluation of the visual pathway. Non-injured optic nerve served as positive control and axotomized optic nerve with no treatment served as negative control.In a parallel set of experiments, the right optic nerve of adult goldfish was crushed or cut (equal number of fish in each group) under deep anesthesia. Two weeks and one month following injury, marker associated with degenerative and regenerative processes were studied in the optic nerve and retina. We injected intra ocular Semaphorin class 3 to goldfish, which the optic nerve was injured, to examine whether the degenerative process could be interrupted. Results: The regenerative process was traced in vivo using Mn2+ enhancing signal. The signal in non-injured optic nerve was detected in the retina, optic nerve, optic tract, lateral geniculate body and visual cortex. The signal in the injured optic nerve was detected only in the vicinity of the retina and a short proximal stump of optic nerve. Axotomized ONs that were treated with either HA or SAPs exhibited marked regeneration of ON. In vitro confocal imaging evaluation confirmed the MRI findings. Collectively, these results demonstrate the potential of bio-materials scaffolds to enhance axonal regeneration. We found that administration of Semaphorin class 3 to injured optic nerve of gold fish disrupted the regenerative process of the injured optic nerve. Conclusion: The optic nerve of lower vertebrates, such as goldfish, is capable of regeneration and regain of function while higher mammals, such as rat, require special modulation of the neuronal environment to enable partial regeneration. CR: A.S. Solomon, None; S. Rosenzweig, None; A. Nitzan, None; A. Barzilai, None. Support: Bi Natural Grant from EC Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 3193-3196 Tuesday, May 5, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 3189 - 3200 / D718 - D729 356. Optic Nerve Injury and Regeneration Organizing Section: EY Contributing Section: RE 3197 - D726 Combination of Transferring CNTF Gene to Retinal Ganglion Cells in vivo and Transplanting Schwann Cells Grafts Conduct to Enhance the Optic Nerve Regeneration in Adult Rats Y. Fang1,2, X. Mo2, W. Guo2, J. Tian2, Y. Wang2, X. Rong2, M. Zhang2, X. Sun2. 1Schepens Eye Research Institute, Boston, MA; 2Eye & ENT Hospital of Fudan University, Shanghai, China. 3198 - D727 Characterization of a Novel Photochemically Induced Ischemic Optic Neuropathy Model J.L. Goldberg1A, Y. Duan1A, W. Kong1A, M. Benny1A, B. Watson1B. ABascom Palmer Eye Inst, BNeurology, 1University of Miami, Miami, FL. Purpose: To promote the injured optic nerve regeneration effectively in the adult mammalian , transplantation of Schwann cells (SCs) in an artificial grafts combining with transferring ciliary neurotrophic factor (CNTF) gene to retinal ganglion cells (RGCs) was tried. Methods: To provide a suitable axonal growth environment, the tissue engineering nerve conduct consisting of SCs cultured in poly-lacticco-glycolic acid (PLGA) conduct was constructed and transplanted to the transected optic nerve stump in adult rats. Meanwhile, transferring CNTF gene into RGCs in vivo by electroporation was used to increase the injured RGCs survival and growth capability. Besides that, SCs was gene-modified in vitro by electroportation to increase their neurotrophic effect. After 4 weeks of transplantation, the effect of axonal regeneration was evaluated by DiI labeling and GAP43 staining of graft sections. Results: By electroporation, CNTF gene was transferred to SCs effectively in vitro which was proven by RT-PCR and immunocytochemistry. The tissue engineering nerve conduct was good biocompatible and held abundant of SCs. Transplantation of CNTF gene modified SCs grafts promoted more axons to regenerate than SC grafts. And With the combinational therapy of transferring CNTF into RGCs in vivo by electroporation, transplantation of CNTF gene modified SCs grafts can reach the best effect. Conclusions: The combinational use of genetically modified tissue engineering nerve conduct to bridge tissue defects and transferring neurotrophic factor gene to RGCs to enhance its intrinsic survival and regenerative capacity may provide new therapeutic strategies for the treatment of optic nerve injuries. CR: Y. Fang, None; X. Mo, None; W. Guo, None; J. Tian, None; Y. Wang, None; X. Rong, None; M. Zhang, None; X. Sun, None. Support: National Natural Science Fund of China Grant NSFC30300379, Natural Science Fund of Shanghai Grant 034119807 Purpose: The mechanisms that lead to neuronal death after axonal injury are poorly understood partly due to the lack of clinically relevant animal models. Here we are using a novel photochemically induced ischemic optic neuropathy (PCI-ION) model to better understand optic nerve stroke. Methods: The left optic nerve from Sprague-Dawley (SD) adult rats was exposed to 532 nm Nd:YAG laser irradiation delivered as high-intensity pulses for 90 seconds immediately after the photosensitizing dye Erythrosin B (ErB) was injected through the femoral vein. Evans blue was used to characterize the vessel leakage and thrombus formation in the optic nerve and DiA was used to check the integrity of retinal circulation. The histological changes after PCI-ION was examined by both H&E staining and immunohistochemistry. RGC survival was quantified by counting the number of retrogradely labeled flurogold-positive cells in the flat mounted retina. Results: PCI-ION led to vessel leakage indicated by Evans blue distribution outside of the vessels in the nerve without interfering the circulation of retina by DiA perfusion. One week after PCI-ion at 200mw intensity, H&E staining of the optic nerve cross sections demonstrated that the optic nerve structure was disrupted and cells were aggregated at the treated area (~700μm in length, 2/3 in depth). Immunohistochemistry revealed that PCI-ION led to glial cell activation. PCI-ION led to retrograde cell death in the corresponding retinal quadrant. Conclusions: We have successfully generated a rodent model of ischemic optic neuropathy. With this model, we can explore in depth the mechanisms leading to neuronal death after axonal injury, and eventually test new therapeutic strategies to enhance survival. CR: J.L. Goldberg, None; Y. Duan, None; W. Kong, None; M. Benny, None; B. Watson, None. Support: American Heart Association (JLG), James and Esther King Foundation (JLG), NEI P30 EY014801 (UM), and an unrestricted grant from Research to Prevent Blindness. 3199 - D728 In vivo Imaging of Retinal Ganglion Cell Axons Within the Nerve Fiber Layer 3200 - D729 Relevance of 24S-Hydroxycholesterol as a Biomarker of Optic Neuropathies A. Kanamori, M.-M. Catrinescu, M. Traistaru, R. Beaubien, L.A. Levin. Ophthalmology, University of Montreal, Montreal, QC, Canada. L. Bretillon1, L. Martine1, B. Pasquis1, C. Fourgeux1, C. Schnebelen1, N. Acar1, I. Björkhem2, A.M. Bron1,3, C.P. Creuzot-Garcher1,3. 1INRA, University of Burgundy, Eye & Nutrition Research Group, Dijon, France; 2Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; 3University Hospital, Department of Ophthalmology, Dijon, France. Purpose: Optic nerve injury causes the loss of retinal ganglion cells (RGCs) and their axons. The reduction in RGC counts over time in axonal injury is well studied, but the correlation with the time course of anterograde and retrograde axonal degeneration is less clear. We longitudinally observed retinal nerve fiber bundles (RNFB) stained with a chloromethyl derivative of fluorescein diacetate (CMFDA) in the living rat after optic nerve injury. Methods: The right optic nerves of Long-Evans rats were transected within the meninges by a transconjunctival approach, sparing the retinal circulation. Three days after transection CMFDA was intravitreously injected to a vitreous concentration of 60 µM. Confocal scanning laser imaging was performed daily with a Heidelberg Retina Angiograph 2 (HRA2) using the fluorescein channel and images exported to ImageJ. Mean fluorescence intensity and number of CMFDA bundles were calculated. A separate group of animals underwent retrograde RGC labeling by overlaying the superior colliculi with Alexa Fluor 488-dextran. Results: RNFB lost 87 ± 15% of their fluorescence by 7 days after injection and 10 days after optic nerve transection, compared with 42 ± 26 % in untransected eyes (p = 0.005, n = 6). Similarly, the number of labeled RNFB decreased by 86 ± 13 % after optic nerve transection, vs. 49 ± 22 % in untransected eyes (p = 0.004; n = 6). To distinguish increased leakage of CMFDA as a result of injury from decreased number of CMFDA-positive axons, another group of animals were injected with CMFDA at 2 and 3 weeks after transection. There were far fewer axon bundles labeled, compared to the number labeled at three days after transection, consistent with a decrease in the number of axons and not just CMFDA leakage. The number of retrograde labeled RGC bodies and CMFDA bundles on HRA2 decreased rapidly between 5 and 7 days after transection. Conclusions: Intravitreal CMFDA can be used to longitudinally monitor RGC axons within the retinal nerve fiber layer in vivo. CR: A. Kanamori, None; M.-M. Catrinescu, None; M. Traistaru, None; R. Beaubien, None; L.A. Levin, None. Support: Canada Institutes for Health Research, Canada Foundation for Innovation, Canada Research Chairs program, Fonds de recherche en ophtalmologie de l’Université de Montréal Purpose: 24S-Hydroxycholesterol is formed by enzymatic oxidation of cholesterol via cholesterol-24S-hydroxylase (CYP46A1) activity in neurons, including retinal ganglion cells and neurons from the inner retina. We investigated whether neurodegeneration could be associated with the release of 24S-hydroxycholesterol in acute neuropathies, and therefore 24S-hydroxycholesterol could be considered as a biomarker of retinal cell degeneration in the course of optic neuropathies. Methods: Retinal neurodegeneration was induced in rats by severe elevation of intraocular pressure. For that purpose, rats were submitted to 532nm-laser photocoagulation of the episcleral veins, limbus and trabecular meshwork. Intra-ocular pressure was monitored in a time course study at 1, 3, 7, 14, 21, 30 and 60 days post laser injury using Tonolab®. Rat retinal and plasma 24S-hydroxycholesterol levels were quantified by gas-chromatography mass spectrometry using deuterated internal standard at the same time points. Plasma levels of 24S-hydroxycholesterol were similarly monitored in patients suffering from anterior ischemic optic neuropathy. Results: Intra-ocular pressure was significantly raised by a factor of five in the laser treated-eyes of the rats compared to fellow eyes, during the first two weeks after photocoagulation, and returned to baseline afterwards. The levels of 24S-hydroxycholesterol were lowered in the first three days in the retina injured by laser, compared to fellow eye. Meanwhile, plasma levels of 24S-hydroxycholesterol were raised by a factor of three. Patients suffering from anterior ischemic optic neuropathy showed increased plasma levels of 24S-hydroxycholesterol, compared to age-matched normal subjects (H=6.86, P=0.009 by Kruskal-Wallis test). Conclusions: Increased plasma levels of 24S-hydroxycholesterol were associated with acute phases of optic neuropathies, suggesting its relevance as a biomarker of retinal neurodegeneration. CR: L. Bretillon, None; L. Martine, None; B. Pasquis, None; C. Fourgeux, None; C. Schnebelen, None; N. Acar, None; I. Björkhem, None; A.M. Bron, None; C.P. CreuzotGarcher, None. Support: PHRC inter-régional Dijon-Nancy Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 3197-3200 Tuesday, May 5, 3:45 PM - 5:30 PM Palm A Paper Session Program Number Range: 3463 - 3469 368. Retinal Ganglion Cell Injury and Regeneration Organizing Section: EY 3463 - 3:45PM Eary Changes in Experimental Anterior Ischemic Optic Neuropathy and Treatment with α-B Crystallin 3464 - 4:00PM In vivo Confocal Scanning Laser Imaging of Retinal Ganglion Cell Superoxide After Optic Nerve Transection Y.J. Liao1A, K. Kaur1A, S. Ousman2, L. Steinman1B, S. Pangratz-Fuehrer1A. A Ophthalmology, BNeurology, 1Stanford, Stanford, CA; 2Clinical Neurosciences, University of Calgary, Calgary, AB, Canada. M.-M. Catrinescu1, A. Kanamori1, K.A. Mears1, R. Beaubien1, L.A. Levin1,2. 1 Ophthalmology, Maisonneuve Rosemont Hospital Research Center, University of Montreal, Montreal, QC, Canada; 2Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI. Purpose: Anterior ischemic optic neuropathy (AION) is due to ischemia of the optic nerve head, leading to significant vision loss. Our goal was to study the early changes following optic nerve head ischemia and to test the efficacy of a potential therapy in experimental AION. Methods: We used a photochemical thrombosis model of AION in mouse, with laserdirected optic nerve head ischemia in the presence of rose bengal. Intracranial flash visual evoked potential (fVEP) recordings and histological methods were utilized. Results: Within days after experimental AION, there was significant optic nerve head swelling, vascular leakage, and selective loss of the peri-papillary microvasculature. Consistent with these ischemic changes, there was functional impairment as demonstrated by a decrease in the amplitude of fVEP responses. Coincident with these histological and functional deteriorations, there were signs of inflammatory cellular reactions, with up-regulation of macro- and microglia. Interestingly, the expression of α-B crystallin (αBC), a small heat shock protein abundant in the lens of the eye, was significantly increased in the optic nerve head and retina at day one following experimental AION. This led us to test αBC as a potential treatment in experimental AION. Injected daily for 3 days following optic nerve head ischemia, αBC did not dampen post-ischemic macro- and microglial responses in wild-type or in αBC knock-out mice. Since significant retinal ganglion cell loss occurs within the first 3 weeks following experimental AION, leading to irreversible vision loss, we tested the effects of a 3-week course of αBC, with weekly fVEP measurements to monitor visual function. After 3 weeks of αBC treatment, there was a significant improvement of the fVEP latencies in the αBC-treated group but not in the salinetreated group, without an improvement in the fVEP amplitudes or the number of surviving retinal ganglion cells. Conclusions: αBC, an important chaperone and key molecule in inflammation and neurodegeneration, was acutely up-regulated in experimental AION. Short-term αBC treatment immediately following optic nerve head ischemia did not have significant effects, while a 3-week course of αBC injections led to a dramatic improvement of the visual pathway signal transmission, consistent with a mechanism of axonal protection. CR: Y.J. Liao, None; K. Kaur, None; S. Ousman, P, P; L. Steinman, P, P; S. PangratzFuehrer, None. Support: Career Award in Biomedical Sciences from the Burroughs Wellcome Foundation, NIH Grant K08 NS044268 Purpose: We previously used in vitro and ex vivo imaging to demonstrate generation of superoxide within axotomized retinal ganglion cells (RGCs). We now describe the use of longitudinal in vivo imaging to study superoxide within retinal ganglion cells after optic nerve transection. Methods: The right optic nerves of Long-Evans rats were transected within the meninges by a transconjunctival approach, sparing the retinal circulation. Both eyes were intravitreously injected with hydroethidine (HEt), which reacts with superoxide to form a fluorophore with a distinct emission profile, to a final concentration of 100 µM. Retinal ganglion cells (RGCs) were identified with retrograde labeling by overlaying the superior colliculi with DiR (20 mg/ml). Confocal scanning laser imaging was performed with a Heidelberg Retina Angiograph 2 (HRA2) using the fluorescein channel for HEt and the indocyanine green channel for DiR. Results were confirmed by immunohistofluorescence. Results: HEt-positive cells could be imaged in vivo within the ganglion cell layer 1 day after optic nerve transection. The number of HEt-positive cells increased to a maximal level 4 days after transection. HEt-positive cells were not present in eyes untransected eyes. HEt-positivity co-localized with RGCs retrograde labeled with DiR. Intravitreal pegylated superoxide dismutase significantly reduced the number of HEt-positive cells (40.6 ± 18.5 vs. 4.8 ± 6.3; p < 0.001). Conclusions: An increase in RGC superoxide can be identified by confocal scanning laser ophthalmoscopy at an early stage after axonal injury. CR: M.-M. Catrinescu, None; A. Kanamori, None; K.A. Mears, None; R. Beaubien, None; L.A. Levin, None. Support: Canadian Institutes for Health Research, Canadian Foundation for Innovation, Canadian Research Chairs program, Fonds de recherche en ophtalmologie de l’Université de Montréal 3465 - 4:15PM Manipulation of Intrinsic Growth Control Pathways to Promote CNS Axon Regeneration-Involvement of PTEN/mTOR Pathway 3466 - 4:30PM Enhanced Retinal Axonal Sprouting Following Optic Nerve Crush in Adult CCL2 Deficient Mice K.S. park, K. Liu, Y. Hu, P. Smith, C. Wang, B. Cai, B. Xu, I. Kramvis, M. Sahin, Z. He. Neurology, Children’s Hospital Boston, Boston, MA. K.-S. Cho, D.-F. Chen. Schepens Eye Research Institute, Department of Ophthalmology and Program in Neuroscience, Harvard Medical School, Boston, MA. The failure of axons to regenerate is a major obstacle for functional recovery after central nervous system (CNS) injury. Removing extracellular inhibitory molecules results in limited axon regeneration in vivo. To test for the role of intrinsic impediments to axon-regrowth, we analyzed cell growth control genes using a virus-assisted in vivo conditional knockout approach. Deletion of PTEN (phosphatase and tensin homolog), a negative regulator of the mammalian target of rapamycin (mTOR) pathway, in adult retinal ganglion cells (RGCs) promotes robust axon regeneration after optic nerve injury. In wild-type adult mice, the mTOR activity was suppressed and new protein synthesis was impaired in axotomized RGCs, which may contribute to the regeneration failure. Reactivating this pathway either by conditional knockout of tuberous sclerosis complex 1 (TSC1), another negative regulator of the mTOR pathway or over-expression of Ras homologue enriched in brain 1 (Rheb1), a direct activator of mTOR pathway also leads to axon regeneration. Thus, our results suggest the manipulation of intrinsic growth control pathways as a therapeutic approach to promote axon regeneration following CNS injury. CR: K.S. park, None; K. Liu, None; Y. Hu, None; P. Smith, None; C. Wang, None; B. Cai, None; B. Xu, None; I. Kramvis, None; M. Sahin, None; Z. He, None. Support: Craig H Neilson Foundation Purpose: Injured CNS including optic nerve has been known of incapable to regenerate the injured axons in adult mammal. In addition to the known astrocyte- and myelinrelated growth inhibitors along CNS pathway, the infiltration of leucocytes may play a role to block optic nerve regeneration. It has been shown that upregulation of CCL2 would regulate infiltration of leucocytes into the lesion area. To test this hypothesis, we performed optic nerve crush in adult C57BL/6J and CCL2 knockout mice and compare the axonal regrowth after injury. Methods: Optic nerve crush was performed in adult CCL2 knockout and C57BL/6J (background-matched control) mice. On day 11 post-injury, 2 μl of an anterograde axon tracer, cholera toxin B subunit (CTB), was injected into the vitreous of the operated eye. On day 14 post-injury, mice were sacrificed and optic nerves were collected and processed for cryosections. To determine axonal regrowth, the sections were incubated with goat anti-CTB antibody, followed by secondary antibody of biotinylated antigoat IgG, and were visualized by Alexa Fluor 546. To determine retinal ganglion cell survival, retinal sections were incubated with primary antibody against beta-IIItubulin and 4’, 6-diamidino-2-phenylindole (DAPI). Number of CTB-positive axons that regenerated past the lesion site was counted at steps of 250 μm away from the crushed site in optic nerve sections. Numbers of beta-III-tubulin- and DAPI-positive cells in the ganglion cell layer were counted in 5 random and non-overlapping areas in each retinal section under 400x magnifications. Results: Little axonal regeneration was observed in wild-type mice. However, absence of CCL2 significantly improved axonal regrowth after optic nerve injury in CCL2 knockout mice as compared to wild-type mice, and the number of regenerating axons counted from CCL2 knockout mice was ten times more than was observed in wild-type mice. Conclusions: Absence of CCL2 provides a permissive environment for axonal sprouting, likely through the suppression of injury-induced activation of microglia and macrophages. CR: K.-S. Cho, None; D.-F. Chen, None. Support: NIH/NEI R01EY017641, Department of Defense W81XWH-04-2-0008, the American Health Foundation, P30 EY003790 (Core grant to the Schepens Eye Research Institute). Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 3463-3466 Tuesday, May 5, 3:45 PM - 5:30 PM Palm A Paper Session Program Number Range: 3463 - 3469 368. Retinal Ganglion Cell Injury and Regeneration Organizing Section: EY 3467 - 4:45PM Tnfr1 Death-Signalling Pathway Is Regulated in the Retina Both After Optic Nerve Transection and Optic Nerve Crush 3468 - 5:00PM Genome-Wide Transcription Profile in Leukocytes of LHON Patients With the 11778 Mutation M. Agudo, F. Nadal-Nicolas, M. Perez-Marin, P. Sobrado-Calvo, L. Nieto-Lopez, M. Salinas-Navarro, M. Vidal-Sanz. Oftalmologia, Universidad de Murcia, Murcia, Spain. T.M. Bosley1,2, K.K. Abu-Amero1. 1Ophthalmology, King Saud University, Riyadh, Saudi Arabia; 2Medicine, Cooper University Hospital, Camden, NJ. Purpose: We have previously demonstrated that TNFR1 and TRADD are up-regulated in optic nerve injured retinas and expressed by axotomized retinal ganglion cells (RGCs) (Agudo et al, Mol Vision 2008, 14:1050-63). Here we further analyse the temporal regulation of FADD and Caspase 8, adaptor and effectors downstream the TNFR1 death signalling pathway, in retinas undergoing intraorbital optic nerve transection (IONT) or crush (IONC) Methods: In control adult albino rats and in ON injured retinas analyzed at 12h, 48h or 7d after IONT or IONC (n=4, per treatment and time point), retinas were either freshly dissected for protein extraction and western blotting, or perfused, frozen and cut on the cryostat on 15µm thick radial sections. RGCs were identified with Fluorogold (FG) applied to both superior colliculi (SCi) one week before ON injury. Sections and westerns were incubated with primary antibodies against FADD and Caspase 8, and revealed with secondary antibodies conjugated to alexa-568 and HRP, respectively. Results: Western blotting assays revealed that Caspase 8 precursor and active forms, and FADD were up-regulated as soon as 12h post-IONT and IONC This upregulation is maintained up to 7dpl. This up-regulation is maintained up to 7dpl. Immunohistofluorescence to radial sections of control and injured retinas showed that both proteins were expressed by RGCs as seen by their co-localization with FG, among other cells of the ganglion cell later. Western blotting assays revealed that Caspase 8 precursor and active forms, and FADD were up-regulated as soon as 12h post-IONT and IONC. Conclusions: The up-regulation of FADD and Caspase 8 after optic nerve injury further implies an active role for the extrinsic apoptotic pathway triggered by TNFR1 in signalling axotomy induced RGC death. CR: M. Agudo, None; F. Nadal-Nicolas, None; M. Perez-Marin, None; P. SobradoCalvo, None; L. Nieto-Lopez, None; M. Salinas-Navarro, None; M. Vidal-Sanz, None. Support: ISCII: CP003/00119, ISCIII PI070225, ISCIII RD07/0062/0001, Fundación Séneca: 04446/GERM/07 and MECSAF-2005-04812 Purpose: We evaluated gene expression in leukocytes of four patients with the 11778 mitochondrial DNA mutation and bilateral optic neuropathy consistent with Leber hereditary optic neuropathy (LHON) and three age, sex, and ethnicity matched controls in order to examine the altered expression of mitochondrial and nuclear genes associated directly or indirectly with mitochondria or the oxidative phosphorylation machinery and to see if a unique gene expression profile could be obtained for LHON. Methods: RNA was extracted from leukocytes and cDNA reverse transcribed and hybridized to Affymetrix Gene Chips. Principle component analysis and the Rate Monotonic Algorithm were performed and further analysis applied to genes with a 2-fold expression difference and p < 0.005 between patients and controls. Results: The gene expression profile of patients with the 11778 mtDNA mutation was significantly different from controls. With the aid of the Gene Ontology Database, the most commonly up-regulated genes (n = 137) were found to be related to the cellular transport (13.8%; 19/137) and transcription (12.4%; 17/137). Similarly, the most commonly down-regulated genes (n = 152) were also related to the cellular transport (17.8%; 27/152) and transcription (18.4%; 28/152). Surprisingly, none of the 13 mitochondrial coded genes and no structural mitochondrial nuclear-encoded genes were differentially expressed. The OPA1 gene was down-regulated, but no other nonstructural nuclear-encoded mitochondrial gene was differentially expressed. Conclusions: The presence of the 11778 mtDNA mutation resulted in a unique gene expression profile compared to controls together with changes in transcription of specific genes that may provide information about LHON disease mechanisms. In particular, down-regulation of OPA1 could be integral to the mitochondriainduced apoptosis that is likely the pathologic process in LHON. CR: T.M. Bosley, None; K.K. Abu-Amero, None. Support: None 3469 - 5:15PM Axonal mtDNA Copy Number Correlates With the Neurodegenerative Pattern in Optic Nerve Cross-Sections of Leber’s Hereditary Optic Neuropathy Patients V. Carelli1, F.N. Ross-Cisneros2, M. Sebastiani 3, C. Travaglini 3, S.S. Salomao 4, A. Berezowski4, M. Moraes5, M.F. Moraes5, A.A. Sadun2, C. Giordano3. 1Neurological Sciences, University of Bologna, Bologna, Italy; 2Doheny Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, CA; 3Experimental Medicine, University La Sapienza, Rome, Italy; 4Ophthalmology, Federal University Sao Paolo, Sao Paolo, Brazil; 5Ophthalmology, Instituto de Olhos de Colatina, Colatina, Espirito Santo, Brazil. Purpose: To describe the correlation between axonal mtDNA amount and pattern of neurodegeneration in optic nerve cross-sections from control and Leber’s hereditary optic neuropathy (LHON) individuals. LHON, a blinding disorder due to mtDNA point mutations affecting complex I, is characterized by selective neurodegeneration of retinal ganglion cells (RGCs). Increased mitochondrial biogenesis is described as a compensatory mechanism in LHON and mtDNA copy number may be relevant for RGCs loss. Methods: We investigated 12 eyes from six controls and 4 eyes from two LHON/11778 patients, collected at autopsy. Retrobulbar optic nerve 5 μm thick cross-sections were stained with Luxol Fast Blue and nerve bundles from temporal, superior, nasal, inferior, and central regions were microdissected by laser capturing. Microdissected areas were measured (μm 2) and subjected to histomorphometric analyses (Metamorph 6.0) to count glial cells. Total DNA was extracted and mtDNA amount was quantified by Real-TimePCR. The number of mtDNA molecules were normalized as mtDNA copy/μm3 (area x 5 μm) or as mtDNA copy/nucleus (glial cells). Pattern of degeneration was evaluated in the LHON optic nerves by immunostaining with antibodies against myelin basic protein and by paraphenylenediamine staining. Results: Content of mtDNA per μ3 in temporal and central regions was significantly lower (p<0.05) than the superior, nasal and inferior regions. Similar results were observed for mtDNA/nucleus ratio. These results fit the profile of neurodegeneration seen in optic nerve cross-section from the LHON patients, where a “butterfly-like” pattern of axonal loss affects first the temporal quadrant, eventually expanding into the superior/inferior quadrants and leaving the nasal the most spared. Conclusions: This study demonstrates that the papillomacular bundle axons of the temporal quadrant are the most vulnerable having the lowest amount of mtDNA. These observations support the proposal that mtDNA copy number is relevant to neurodegeneration of RGCs and increase of mitochondrial biogenesis may be a successful compensatory mechanism. CR: V. Carelli, None; F.N. Ross-Cisneros, None; M. Sebastiani, None; C. Travaglini, None; S.S. Salomao, None; A. Berezowski, None; M. Moraes, None; M.F. Moraes, None; A.A. Sadun, None; C. Giordano, None. Support: Telethon Grant GGP06233 to VC Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 3467-3469 Wednesday, May 6, 8:30 AM - 10:15 AM Palm A Symposia Program Number Range: 3862 - 3865 402. Suppression in Strabismus and Amblyopia - Minisymposium Organizing Section: EY Contributing Section: VI 3862 - 8:30AM A Million Neurones Can Be Wrong. 3863 - 8:40AM The Measurement And Treatment Of Suppression R.A. Harrad. Ophthalmology, Bristol Eye Hospital, Bristol, United Kingdom. R.F. Hess. Ophthalmology, McGill University, Montreal, QC, Canada. In amblyopia much of the visual input of the amblyopic eye, amounting to about one million ganglion cell axons, is suppressed during binocular viewing. I shall introduce this symposium by outlining some of the physiological processes that are thought to be instrumental in bringing about this powerful effect and briefly summarise some of the experimental evidence that has been gathered in over 100 years of activity in this field of research. CR: R.A. Harrad, None. It has been established that in amblyopia, information from the amblyopic eye (AME) is not combined with that from the fellow fixing eye (FFE) under conditions of binocular viewing. However, recent evidence suggests that mechanisms that combine information between the eyes are intact in amblyopia. The lack of binocular function is most likely due to the imbalanced inputs from the two eyes under binocular conditions (Baker, Meese, Mansouri & Hess, 2007b). We have measured the extent to which the information presented to each eye needs to differ for binocular combination to occur and in doing so we quantify the influence of interocular suppression. We quantify these suppressive effects for suprathreshold processing of global stimuli for both motion and spatial tasks. The results confirm the general importance of these suppressive effects in rendering the structurally binocular visual system of a strabismic amblyope, functionally monocular. CR: R.F. Hess, None. 3864 - 9:10AM Neural correlates of suppression 3865 - 9:40AM Mapping of Visual Field Suppression in Strabismus A.M. Norcia. Smith-Kettlewell Eye Res Inst, San Francisco, CA. J.C. Horton. Ophthalmology, Univ California - San Francisco, San Francisco, CA. Due to the misalignment of their eyes during early development, most strabismic observers have no functional stereopsis. Nevertheless, they do have binocular interactions, primarily of a suppressive or inhibitory kind. We have used the Visual Evoked Potential to explore the electrophysiological characteristics of suppression in strabismic patients with and without anisometropia. We find evidence consistent with strabismic suppression being a component of an aberrant stereo network that when operative, prevents diplopia in the absence of stereopsis. We have also found a special case where suppression fails in a disparity-dependent fashion. CR: A.M. Norcia, None. We mapped regional patterns of perceptual suppression by testing the visual fields dichoptically in 9 strabismic humans with no history of diplopia (3 esotropes and 6 exotropes). Subjects wore red/blue dichroic filter goggles to allow dichoptic stimulation. They fixated a monocularly seen (red or blue) central target rear-projected onto a translucent tangent screen. Without breaking fixation, subjects were asked to identify the apparent color of a peripheral stimulus flashed briefly (200 ms) on the screen. The peripheral stimulus was purple; its reported color (“red” or “blue”) revealed which eye’s image was perceived at that locus. The position of each eye was monitored continuously with infrared video eye trackers to insure accurate fixation on the central target and to monitor the location of the deviated eye. Using this perimetric technique, we generated a perceptual map for each eye under conditions of binocular stimulation. Normal control subjects, rendered diplopic with a prism, reported two stimuli (red and blue) at all retinal locations except at their blind spots. In contrast, the strabismic subjects reported a single stimulus (either red or blue) at the majority of field locations. Their binocular maps showed regional perceptual suppression and dominance for each eye. CR: J.C. Horton, None. Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 3862-3865 Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204 415. Neuro-Ophthalmology Organizing Section: EY 4017 - A179 An Analysis of Patient Clinical and Laboratory Characteristics in Relation to Temporal Artery Biopsy Results 4018 - A180 Biopsy Positive Temporal (Giant-cell) Arteritis - Is a Higher Inflammatory Response Associated With Visual Loss? M.R. Melson, L.A. Mawn. Ophthalmology, Vanderbilt Eye Institute, Nashville, TN. S. Trikha, A. Lockwood, J. Kirwan. Ophthalmology Department, Portsmouth, UK, Portsmouth Hospitals’ NHS Trust, Portsmouth, United Kingdom. Purpose: Clinical signs, symptoms and elevated serum inflammatory markers may support the diagnosis of giant cell arteritis (GCA), but a positive temporal artery biopsy (TAB) is often considered paramount in confirming it. Physicians must ultimately use clinical judgment in choosing patients on whom to perform TAB, but laboratory and other objective data may help support this decision. We examined our institutional experience over the past 10 years to help determine what patient characteristics were most associated with a positive TAB. Methods: After institutional review board approval, we obtained the list of all patients at our institution that had undergone TAB from 1997-2008. Data on demographics, indications for TAB, relevant laboratory values, surgical service, biopsy specimen length, and biopsy results were collected from the patients’ charts. Data were analyzed to determine if there were significant differences in the clinical and laboratory characteristics of patients with different biopsy results. Results: Two hundred patients underwent TAB or ligation in the study period. Twentyfour patients were excluded for insufficient data or because the procedure was not performed to evaluate for GCA. Of the 176 biopsies included, 26 (15%) were positive and 154 (85%) were negative. The mean age of patients with a positive TAB was 74 and of those with negative biopsies, it was 68 (p=0.004). Among patients with positive TAB, 69% were female and 31% were male while the distribution for patients with a negative biopsy was 73% and 27%, respectively. The mean erythrocyte sedimentation rate (ESR) for patients with a positive biopsy was 82 mm/hr and that for patients with a negative biopsy was 60 mm/hr (p=0.0005). The average length of positive biopsy specimens was 2.8 cm and that for negative specimens was 3.3 cm (p=0.19). Conclusions: Older age and higher sedimentation rates are correlated with a greater likelihood of a positive TAB in patients suspected of having GCA. Though more women undergo TAB, the proportion of men and women with positive biopsies is not significantly different. Longer TAB specimens were not correlated with a higher likelihood of a positive pathologic diagnosis. CR: M.R. Melson, None; L.A. Mawn, None. Support: Research to Prevent Blindness unrestricted departmental grant 4019 - A181 Six-Year Results of a Protocol for the Early Diagnosis of Temporal Arteritis in an Ophthalmological Setting E. Heron, A. Affortit-Demoge, I. Rossignol, N. Sedira, S. Feldman-Billard. Service de Medecine Interne, CHNO des Quinze-Vingts, Paris, France. Purpose: Preventing ocular complications remain the main goal of the treatment of temporal arteritis (TA). We reviewed our last 6-year experience of TA-related ocular manifestations at a national eye center, and of our diagnostic strategy for TA. Methods: Retrospective study of medical records: since august 2001, all patients with ischemic ocular manifestations potentially related to TA had C-reactive protein and erythrocyte sedimentation rate measured in emergency, their ocular and general manifestations were recorded by an internist. Patients older than 55 years with acute anterior ischemic optic neuropathy (AAION) systematically had temporal artery biopsy, whereas those with other ocular manifestations qualified for a biopsy in the presence of systemic signs and/or laboratory abnormalities. The diagnosis of TA was based on histological signs, or in presence of a high level of clinical and/or biological suspicion. Results: Between august 2001 and september 2007, a temporal artery biopsy was done in 305 patients, 265 of them (87%) with AAION. A diagnosis of TA was made in 82 patients (27%), biopsy-proven in 59 of them (72%) and despite a negative biopsy in 23 (28%). Among these 82 patients, 71 (86%) had a definitive vision loss due to AAION in 67 (82%) and to central retinal artery occlusion in 4 (5%), whereas 11 (13%) had only transient ocular manifestations (6 had diplopia and 5 had transient monocular blindness) which didn’t progress to a definitive vision loss after steroid treatment (pulse methylprednisolone). Among patients with AAION, a positive biopsy was obtained in 47 cases, of whom 11 (23%) had occult TA (no systemic sign or symptom) and 3 (6%) had normal laboratory parameters before steroid treatment. Conclusion: Making an early diagnosis of TA in patients older than 55 years in front of transient ocular ischemic manifestations, or by systematic temporal artery biopsy in those with AAION, is not a rare opportunity and is efficient to prevent further vision loss. CR: E. Heron, None; A. Affortit-Demoge, None; I. Rossignol, None; N. Sedira, None; S. Feldman-Billard, None. Support: None Purpose: To investigate the correlation with inflammatory markers of patients with biopsy proven Temporal Arteritis. Secondary outcomes were to assess socioeconomic status and overall incidence Methods: All patients referred for Temporal Artery biopsy at a single centre over a three year period were included. Inflammatory markers Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP) and serum platelet count were compared between biopsy positive and negative samples, along with visual loss and no visual loss groups. Index of deprivation scores from the national database were compared to a cataract surgery group (control) to determine socioeconomic status. Results: Biopsy positive age adjusted incidence was 29.3/100000. 111 Temporal Artery biopsies were performed; 33 were positive cases (B+ve) and 78 negative for GCA(B-ve). Mean age at biopsy was 74.5 years. 93% of cases referred for biopsy were subsequently diagnosed with GCA on clinical grounds. Mean CRP was 50.75 in the B-ve group versus 98.0 in the B+ve group (p<0.001), and mean ESR was 53.9 (B-ve) versus 69.9 (B+ve) (p<0.018). Mean platelet count was 359.7 (B-ve) compared to 438.8 (B+ve) (p<0.001). A higher inflammatory response was not observed in B+ve visual loss group versus B+ve no visual loss (p <0.847, Mann Whitney U test). Statistically insignificant differences in socioeconomic status were found in biopsy positive group compared to controls (p=0.112) Conclusions: Biopsy positive GCA was associated with significant elevations in serum platelet count, ESR and CRP levels compared to biopsy negative GCA, although visual loss in positive samples did not appear to correlate with inflammatory marker levels. GCA appears unrelated to socioeconomic status in this cohort. A large proportion of biopsies were negative or inconclusive - warranting strict criteria for biopsy referral. CR: S. Trikha, None; A. Lockwood, None; J. Kirwan, None. Support: None 4020 - A182 Asymptomatic Papilledema in Morbidly Obese Patients: A Prospective Study D.G. Chu, W. Smith, C.M. Krispel, M.R. Ali, J.L. Keltner. Ophthalmology, UC Davis Medical Center, Sacramento, CA. Purpose: Idiopathic Intracranial Hypertension (IIH) is associated with obesity, however when asymptomatic, IIH is difficult to diagnose in a primary care setting because its sentinel finding is papilledema. Asymptomatic IIH has been estimated in some populations to be as high as 5%-24%. It is unknown if previously proposed screening for asymptomatic IIH based on previously published rates of asymptomatic IIH can be validated by a similarly high incidence of asymptomatic IIH in morbidly obese patients. The purpose of this study was to determine the rate of asymptomatic papilledema found on non-mydriatic fundus imaging of morbidly obese patients in a bariatric surgery clinic. Methods: This was a prospective study. All morbidly obese patients (BMI >35) seeking bariatric surgery who consented to the study and had no visual opacity preventing a high quality fundus photo were included. Non-mydriatic fundus images were taken by trained clinic personnel. Images were reviewed by an ophthalmologist, and optic nerves were evaluated for papilledema. Patients suspected of having an optic nerve abnormality had a subsequent clinical exam by a neuro-ophthalmologist. Results: 140 patients met the inclusion criteria for the study, 83.8% were female, with a mean age of 44.9 years. The mean BMI was 47.8. Ocular abnormalities were noted in 6 patients. Only one patient had subtle bilateral optic disc edema and referred for full neurological IIH work-up. Other findings included optic nerve hyaloid remnant, optic nerve drusen, epiretinal membrane, congenital macular scar, and proliferative diabetic retinopathy. The rate of ocular pathology found in our study was 4.3% (6 of 140 patients). The rate of asymptomatic papilledema in our study was 0.7% (1 of 140 patients). Conclusions: The non-mydriatic camera can be used successfully in the primary care setting to detect even subtle optic disc edema. Many undiagnosed ocular findings were found in our study. Given the low rate of asymptomatic papilledema in this obese population, further studies are needed to determine if previously published rates of asymptomatic IIH and the association between obesity and IIH can be validated. CR: D.G. Chu, None; W. Smith, None; C.M. Krispel, None; M.R. Ali, None; J.L. Keltner, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4017-4020 Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204 415. Neuro-Ophthalmology Organizing Section: EY 4021 - A183 The Diagnostic Yield of Optic Nerve Ultrasonography for Differentiating Papilledema From Pseudopapilledema in Eyes With Swollen Optic Discs 4022 - A184 Evaluation of Optic Nerve Head Drusen Using Spectral-domain OCT (Spectralis) M. Neudorfer, M. Siegman Ben-Chaim, C. Stolovitch, G. Dotan, A. Kesler. Department of Ophthalmology, Tel-Aviv Medical Center, Tel Aviv, Israel. L. Storm, R. Keshavamurthy, V. Brar, K.V. Chalam, S. Grover. Ophthalmology, University of Florida, Jacksonville, FL. Purpose: Swollen discs may be a sign of a life-threatening condition due to increased intracranial hypertension (papilledema), or a sign of benign conditions (pseudopapilledema) like optic nerve head drusen It is not uncommon to have difficulty in differentiating between those conditions. The goal of this study was to show that optic nerve ultrasonography is a reliable, accurate, readily available and low-cost tool to differentiate papilledema from pseudopapilledema. Methods: Forty-four patients with bilateral swollen discs were prospectively evaluated. They all underwent comprehensive medical and ophthalmological examinations, imaging (brain and orbit CT/MRI) and a lumbar puncture, as well as optic nerve ultrasonography for detecting pathological widening of the nerve. We compared the optic nerve ultrasonographic findings to the final diagnosis that had been reached after the workup and follow-up, and calculated the sensitivity and specificity of optic nerve ultrasonography for differentiating papilledema from pseudopapilledema. Results: Twenty-three males and 21 females aged 12±6.5 y (2.5-30.5) participated. The average follow up was 1.5 y. The calculated sensitivity of the examination was 95%, with a specificity of 58%, a positive predictive value of 66%, a negative predictive value of 93% and a correlation coefficient of +0.56 (p<0.001). Conclusions: According to our results evaluation of optic nerve head by ultrasonography had high sensitivity and specificity. Since this was a historic prospective study and not a case-control study, it was possible to calculate the positive and negative predictive values of the procedure for detecting papilledema. This information gives a statistical basis for decision-making when determining the etiology of bilateral swollen discs. According to our findings , optic nerve ultrasonography has significantly higher sensitivity than funduscopy. As such, a combination of a thorough clinical examination and optic nerve ultrasonography may be definitive and render further workup unnecessary in some cases. CR: M. Neudorfer, None; M. Siegman Ben-Chaim, None; C. Stolovitch, None; G. Dotan, None; A. Kesler, None. Support: None Purpose: Optic nerve head drusen (ONHD) are white calcareous deposits, seen either superficially on the optic nerve head or buried within it. Diagnosis of ONHD is made by one or more ways: clinical exam, autofluorescence, ultrasound of the optic nerve, CT scan and/or visual field examination. The present study describes features of ONHD based on another diagnostic modality, the spectral-domain OCT (Spectralis). Methods: This is an observational case series of 5 patients with bilateral ONHD with a best-corrected visual acuity of 20/20 and no other posterior segment pathology. All the patients underwent fundus photography, fundus autofluorescence, B-scan ultrasonography, Spectralis OCT and Humphrey 30-2 threshold visual fields. Results: All 5 patients had surface ONHD which were autofluorescent and echodense on B-scan ultrasonography. Spectralis OCT findings in the corresponding areas include ‘scattered spots with high reflectivity’ casting a shadow underneath. The reflectivity can be distinctly differentiated from the blood vessels on the optic nerve. Two thirds of the patients had an arcuate scotoma on the Humphrey visual fields. No correlation was found between the changes on Spectralis OCT with that of visual field. Conclusions: Spectralis OCT is another useful ancillary investigation in the diagnosis of ONHD and we describe the features in the present study. CR: L. Storm, None; R. Keshavamurthy, None; V. Brar, None; K.V. Chalam, None; S. Grover, None. Support: Foundation Fighting Blindness, Inc., Owings Mills, Maryland. 4023 - A185 Increased Risk in Patients With Optic Disk Drusen for an Acute Non Arteritic Anterior Ischemic Optic Neuropathy 4024 - A186 Assessment of Sleep Apnea in NAION Patients M. Schargus, E. Gramer. Department of Ophthalmology, University Wuerzburg, Wuerzburg, Germany. Purpose: To evaluate: 1. the prevalence of NAION in patients with ODD 2. risk factors compared to control groups. Methods: 120 patients with uni- or bilateral ultrasonographic confirmed ODD were prospectively, consecutively examined and standardized documented between 1987 and 2008. We evaluated whether there are any significant differences between three patient groups: 1. 14 patients with ODD and NAION, 2. 106 patients with ODD without NAION, 3. 420 patients from literature (1) with NAION without ODD in: age of the patient at diagnosis, gender, vascular risk factors (hypertension, heart attack, cardiopathy, hyperlipidemia), visual acuity (VA), mean stage of visual field loss (VFL) and topography of VFL. Unpaired t-test was used for statistics. Results: 1. 14 out of 120 patients with ODD presented at diagnosis an acute unilateral NAION (10.3%). 2. Mean age at diagnosis: Patients with ODD and NAION were significantly younger than patients with NAION without ODD (43,6±18,9 vs. 66,0±8,7 years)(p=0,06). Patients with ODD without NAION were not significant younger than patients with ODD and NAION (42,5±20,0 vs. 43,6±18,9 years) (p=0,8). Gender distribution showed a higher prevalence of females in all three groups and no significant difference between the three groups (females: 61,5% vs 61.3% vs 61,7%). Vascular risk factors were less frequent in the group with ODD and NAION (36%) compared to patients with NAION without ODD (57,9%). Visual acuity was significantly better in patients with ODD and NAION which had in 79% a visual acuity better than 20/64 than patients with NAION without ODD (35%). Patients with ODD without NAION had in 92,6% a VA better than 20/64. Topography of VFL was similar in all patients with NAION with or without ODD presenting most commonly VFL in the inferior hemifield (57% vs 46 %). Conclusion: In patients with ODD acute NAION is more prevalent in a younger age than in patients without ODD. In the group of 106 patients with ODD without NAION we found that the higher the age of the patients the higher the frequency of superficially visible ODD. Therefore we suggest that NAION may occur more often in eyes with buried or less visible ODD than in eyes with superficially visible ODD. Further studies are required. Every tenth referred patient with ODD showed an association with NAION. Therefore ODD patients are at increased risk for NAION. (1) Ischemic Optic Neuropathy Decompression Trial Study Group: Characteristics of patients with NAION eligible for the Ischemic Optic Neuropathy Decompression Trial, Arch Ophthalmol. 1996 Nov;114(11):1366-74. CR: M. Schargus, None; E. Gramer, None. Support: None D.T. Nguyen1A, Y. Emoto2, H. Emoto3, M. Wang1A, T. Zavora4, A. Avakian1A, D. Aggarwal1A, D.J. Levendowski4, J. Sebag5,1, A.A. Sadun1A. ANeuro-Ophthalmology, 1USC Doheny Eye Institute, Los Angeles, CA; 2Department of Neuro-Ophthalmology, Inouye Eye Hospital, Tokyo, Japan; 3Department of Ophthalmology, Tokyo Medical and Dental University, Tokyo, Japan; 4Advanced Brain Monitoring, Inc., Carlsbad, CA; 5VMR Institute, Huntington Beach, CA. Purpose: To measure and compare parameters of obstructive sleep apnea (OSA) in NAION patients and in controls (non-NAION) using in-home sleep studies. Method: 9 NAION patients (7 males, 2 females, mean age 59) and 4 controls (4 females, mean age 51) were recruited, given a history form and sleep log, instructed on the usage of the Apnea Risk Evaluation System Unicorder (Advanced Brain Monitoring, Inc, Carlsbad, CA), and sent home to acquire 2-3 nights of sleep study data. Each night, the Unicorder provided continuous 7 hour recordings of oxyhemoglobin saturation and pulse rate (reflectance pulse oximeter), snoring (microphone), head movement and position (accelerometers), nasal airflow (nasal pressure transducer), and respiratory effort by forehead venous pressure. Questionnaire and Unicorder data were masked and submitted for automated analysis with quality control review. An apnea hypopnea index with 4% desaturation (AHI-4%) and AHI with 1% desaturation (AHI-1%) were calculated. Results: Using AHI-4%, 4/9 NAION patients (44%) had AHI > 5 and 2/9 (22%) had AHI > 15. Using AHI-1%, all NAION patients (100%) had AHI > 5, and 6/9 (67%) had AHI > 15. Of the non-NAION controls, three had AHI-4% < 5 and 1 had AHI-4% = 6. Applying the AHI-1% criteria, three had AHI > 5, however none had AHI-1% > 15. Using either the 4% desaturation or 1% desaturation criteria, the distribution of AHI values were greater in the NAION patients as compared to the non-NAION controls. Conclusions: The results support previous reports of an increased prevalence of OSA in NAION patients. The Unicorder may be used in the home setting to measure parameters of OSA in NAION patients. CR: D.T. Nguyen, None; Y. Emoto, None; H. Emoto, None; M. Wang, None; T. Zavora, Advanced Brain Monitoring, Inc, E; A. Avakian, None; D. Aggarwal, None; D.J. Levendowski, Advanced Brain Monitoring, Inc., I; J. Sebag, None; A.A. Sadun, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4021-4024 Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204 415. Neuro-Ophthalmology Organizing Section: EY 4025 - A187 Ethambutol Toxicity Presenting as Reversible Bitemporal Hemianopia in Patients Being Treated for Mycobacterium Avium Complex 4026 - A188 Magnetic Resonance Imaging Distinguishes Optic Perineuritis From Typical Optic Neuritis T.A. Mendel1, D.A. Chesnutt2. 1University of Virginia, Charlottesville, VA; 2 Ophthalmology, University of North Carolina, Chapel Hill, NC. A. Gupta1, M.J. Kupersmith1,2, D. Meltzer3. 1Ophthalmology, New York Eye and Ear Infirmary, New York, NY; 2Institue for Neurology and Neurosurgery, Roosevelt Hospital, New York, NY; 3Radiology, St. Luke’s/Roosevelt Hospital Center, New York, NY. Purpose: Reported visual toxicities from ethambutol are variable in presentation and degree of reversibility. Methods: Case series of patients with ethambutol visual toxicity. Results: Four patients presented with a bitemporal hemianopia. The visual fields of one patient are featured in the attached figures. Three of the four patients were followed and the visual loss was reversible over approximately one year after discontinuation of the ethambutol. The fourth patient is being followed. A fifth patient presented with bilateral cecocentral defects and was referred back to the local ophthalmologist for follow up. Conclusions: In patients being treated with ethambutol for Mycobacterium avium complex, reversible bitemporal hemianopia seems to be the most common presentation of ethambutol toxicity. It is possible that infection with Mycobacterium avium complex predisposes the optic chiasm rather than the optic nerves to uptake of ethambutol and that the optic chiasm may be more resistant to permanent damage than the optic nerves. Previous reports of severe permanent optic neuropathy in patients being treated for Mycobacterium tuberculosis may be the result of synergistic damage to the anterior visual pathways by the combination of ethambutol and infection with Mycobacterium tuberculosis. CR: T.A. Mendel, None; D.A. Chesnutt, None. Support: None 4027 - A189 The Rate of Visual Loss From Stretch Optic Neuropathy Purpose: The clinical presentations and features of several disorders that are due to presumed inflammation of the optic nerve sheath (perineuritis) are similar to optic neuritis, but perineuritis is not associated with development of MS and may require systemic investigation. We hypothesized that MRI features can differentiate between the two disorders. Method: During the period from 2004-2008, we diagnosed 10 patients with optic perineuritis and 170 patients with typical optic neuritis (18-50 yrs). We reviewed the records for presenting symptoms (including pain on eye movement), clinical signs, age, gender, visual acuity, mean deviation for 24-2 Humphrey (MD in db), and optic disc features. We evaluated fat suppressed gadolinium enhanced T1-weighted and short tau inversion recovery (STIR) orbital MRI in all patients for presence of abnormal enhancement of the optic nerve or of the optic nerve sheath alone, and abnormal signal in the optic nerve. Results: For perineuritis patients, the average age was 34 yrs (range: 12-48 yrs); 9 were females; at presentation 8 had visual acuity > 20/40; 5 had optic disc swelling; 9 had pain on eye movement, and MD ranged from -1.3 to -31 db. Treatment with intravenous methylprednisolone or high dose oral prednisone, followed by a gradual withdrawal, normalized the visual acuity and visual field in 5/7 patients. The visual acuity, but not the field, improved in 1; and 1 had progressive vision loss despite high dose steroid therapy. In 3 patients without vision loss, pain resolved with oral nonsteroidal antiinflammatory agents. All perineuritis eyes (none unaffected eyes) showed abnormal enhancement of the optic nerve sheath but not of the optic nerve. Abnormal optic nerve signal on STIR occurred in 2. No perineuritis patients had abnormal signal of brain white matter. No optic neuritis patients had abnormal enhancement of the optic nerve sheath alone. Conclusion: MRI performed in patients suspected of acute optic neuritis should include orbital views with T1 fat suppression and gadolinium and STIR sequences in order to differentiate perineuritis. This will allow proper counseling, workup and treatment implementation. CR: A. Gupta, None; M.J. Kupersmith, None; D. Meltzer, None. Support: None 4028 - A190 Immunohistochemical Evaluation of S100A12 (Calgranulin C) in Alzheimer Disease Optic Nerves L.N. Johnson, C.R. Soni. Ophthal-Sch of Med, University of Missouri, Columbia, MO. Purpose: An important, though not well recognized, cause of thyroid related optic neuropathy is stretch optic neuropathy. Of the few reported cases, none has documented the rate of vision loss due to continuous stretching of the optic nerve. Animal models have provided information on the tensile strength of the optic nerve, but to our knowledge no in vivo studies of the tensile strength of the human optic nerve have been reported. We present 3 cases of stretch optic neuropathy, one of which provided a unique opportunity to quantify and estimate the rate of vision loss from progressive stretching of the optic nerve. Methods: Retrospective chart review of 3 cases of stretch optic neuropathy. Results: All cases presented with blurry or spotty vision. Best corrected visual acuity ranged from 20/20 to 20/40. Automated perimetry showed arcuate scotoma visual field defects. The range of proptosis was 24 to 27 mm on Hertel exophthalmometry. Ocular motility was normal. Two cases had dot hemorrhages in the fundus simulating venous stasis retinopathy. Computed tomography showed thin extraocular muscles and expanded orbital fat volume. Orbital decompression improved the visual function. One case had progressive visual field loss over a 9-month period, providing a unique opportunity to quantify and estimate the rate of vision loss from progressive stretching of the optic nerve to complete blindness to be 775 days from onset of visual symptoms. Conclusions: Stretch optic neuropathy is an infrequent, but potentially reversible, cause of visual loss and blindness from thyroid associated optic neuropathy. CR: L.N. Johnson, None; C.R. Soni, None. Support: Research to Prevent Blindness, Inc. N.V. Hunter, D. Aggarwal, F.N. Ross- Cisneros, A.A. Sadun. Neuro-Ophthalmology, USC/Doheny Eye Institute, Los Angeles, CA. Purpose: S100A12 belongs to the S100 family of calcium-binding proteins. Of this S100 family, S100A2 which can be released by brain macrophages, microglia, and neutrophils in microvasculature , and can act as a ligand to the receptor for advanced glycation end products (RAGE). S100A12 has been shown to be involved with inflammation, the initiation of amyloidosis, and high-molecular-weight insoluble protein aggregates, in the brains of Alzheimer’s disease (AD) patients. Therefore, the aim of this study was to investigate the presence of S100A12 (Calgranulin C) in AD optic nerves for its possible role in optic neuropathy. Methods: Optic nerve specimens were obtained at autopsy from twelve patients with AD and compared to six normal age-matched control tissues. AD tissues were supplied by our Alzheimer’s Disease Research Center (ADRC) and controls were purchased through local eye banks. Tissues were immersion fixed in neutral buffered formalin, dissected into cross-sectional profiles just proximal to the globe, then processed and embedded into paraffin blocks. Sections were cut at 5 µm and immunostained, using an indirect method with horseradish peroxidase and diaminobenzidine as the substratechromogen, with a mouse anti-human S100A12 monoclonal antibody at a dilution of 1:50. Light microscopic images were viewed on a Zeiss Axioskop microscope and captured by a digital camera and saved to a computer. Results: Immunoreactivity for S100A12 in AD optic nerves appeared as circular plaquelike structures of various sizes often possessing an eccentrically placed large vacuole, “punctate” staining in the cytoplasm of glial cells, and axonal elements. The brains of the same patients demonstrated similar plaque-like structures staining positive for S100A12. In contrast, age matched controls demonstrated very little staining for S100A12 (Calgranulin C) protein in optic nerves and brains. Conclusions: S100A12 was identified immunohistochemically in the optic nerves of AD patients. The pattern of staining suggests that S100A12 is associated with a plaque-like structure similar to lesions found in the brains of the same patients. Thus, our findings suggest that S100A12 may play a role in activation of the RAGE pathway toward inflammation, protein aggregate, and plaque formation associated with AD optic neuropathy. CR: N.V. Hunter, None; D. Aggarwal, None; F.N. Ross- Cisneros, None; A.A. Sadun, None. Support: Research to Prevent Blindness, Oakley Alzheimer’s Research Foundation, NIH Grant EY03040 Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4025-4028 Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204 415. Neuro-Ophthalmology Organizing Section: EY 4029 - A191 Anterior Ischemic Optic Neuropathy and Retinal Artery Occlusion: Check-Up Interest During Hospitalization 4030 - A192 Ocular, Neurological and Endocrine Abnormalities in Children With Unilateral Optic Nerve Hypoplasia A. Feldman, P.-L. Cornut, M. De Bats, C. Burillon, P. Denis. Pavillon C - E Herriot Hospital, Lyon, France. L.L. Cooper, W.F. Astle, K.G. Romanchuk. Department of Surgery, University of Calgary, Calgary, AB, Canada. Purpose: To evaluate a standard check-up during hospitalization for patients presenting anterior ischemic optic neuropathy (AION) or retinal artery occlusion (RAO). Methods: It was a prospective study. The standard check-up was the following one: ESR, CRP, CBC (on emergency), PT, aPTT, fibrinogen, antiphospholipid antibodies, serum protein electrophoresis, homocysteinemia, fasting blood sugar, HbA1c, cholesterol, triglycerides, ambulatory blood pressure monitoring, carotid doppler ultrasound, echocardiography, ECG, cardiologic visit, brain MRI or CT, visual field, fluorescein angiography and temporal artery biopsy at the slightest clinical sign of giant cell arteritis. Results: 46 patients were included. Mean age was 73 years (47-92). CRAO occured in 19 patients (41.3%), BRAO in 6 (13%) and AION in 21 (45.7%). Mean hospitalization duration was 8 days (2-22). AION was bilateral in 2 cases. 6 patients had no atherosclerotic risk factor. Risk factors were already balanced in 11 cases of 46 (23.9%). In 13 cases, a therapic modification has been made to balance risk factors. Corticotherapy has been started in 8 cases (6 AION, 2 RAO); giant cell arteritis was proved in 2 cases (2 AION) and highly suspected in 6 cases. In 8 cases (17.4%), the patient had to be transfered in another specialized service while he was hospitalized (internal medicine, cardiovascular, resuscitation). In 63% of the cases, standard check-up realized during hospitalization led to a change of treatment. Underlying disease was potentially serious and needed an urgent care in a great number of cases. Conclusions: Standard check-up during hospitalization allowed in this study a rapid multidisciplinary care adapted to RAO and AION. A therapeutic change has been established in 2 cases out of 3 and almost 1 patient out of 5 has been transfered in a specialized service. CR: A. Feldman, None; P.-L. Cornut, None; M. De Bats, None; C. Burillon, None; P. Denis, None. Support: None Purpose: Children with bilateral optic nerve hypoplasia usually present with bilateral nystagmus and require investigation for neurological and endocrine abnormalities. Fewer children present with unilateral optic nerve hypoplasia and less has been reported on this disorder. The aim of this study is to examine the ocular features as well as the neurological and endocrine abnormalities of children with unilateral optic nerve hypoplasia. Methods: A retrospective chart review was performed and data was obtained on ocular, neurological and endocrine function Results: Of the 9 patients (7 girls; 2 boys) with unilateral optic nerve hypoplasia, 5 had right optic nerve hypoplasia and 4 had left optic nerve hypoplasia.Two patients had bilateral nystagmus, 1 patient had nystagmus in the affected eye and the remainder of the patients did not have nystagmus. Vision in the eye with optic nerve hypoplasia varied from 20/40 to no light perception. Four patients attempted occlusion therapy and improvement in vision was seen in 1 patient. Strabismus was present in 8 patients (5 esotropia; 3 exotropia). Strabismus surgery was performed in 4 patients and all patients had improvement in eye alignment. One patient had a metabolic abormality in glucose management and 1 patient had neurological abnormalities. Conclusions: Children with unilateral optic nerve hypoplasia have different ocular presentation than children with bilateral optic nerve hypoplasia. Children with unilateral optic nerve hypoplasia have a lower frequency of neurological and endocrinological abnormalities. These finds may suggest a different mechanism for the development of unilateral optic nerve hypoplasia than bilateral optic nerve hypoplasia. CR: L.L. Cooper, None; W.F. Astle, None; K.G. Romanchuk, None. Support: None 4031 - A193 Perinatal Onset Static Encephalopathy: An Underrecognized Cause of Optic Nerve Head Cupping in Children 4032 - A194 A Comparison of Multifocal ERG and Frequency Domain OCT Changes in Patients With Abnormalities of the Outer Retina S. kedar1A, D. Ghate1B, V. Vedanarayanan1C, N. Mungan1B, J.J. Corbett1A, C.J. Chen1B. A Neurology, BOphthalmology, CPediatric Neurology, 1University of Mississippi Medical Center, Jackson, MS. E.A. Dale1A, K.Y. Kay1A, J.G. Odel1B, V. Greenstein1B, D.C. Hood1C. APsychology, B Ophthalmology, CPsychology, Ophthalmology, 1Columbia University, New York, NY. Introduction: To evaluate optic nerve head (ONH) pallor and cupping in children with perinatal onset static encephalopathy (POSE) and its association with age of onset, type of cerebral palsy (CP), ambulation and neuro-radiologic abnormalities. Methods: 42 consecutive children with POSE (without lasered retinas or intraocular disease) were included. ONH was evaluated independently by 2 ophthalmologists by dilated indirect ophthalmoscopy. A child’s ONH were labeled as large cup (cup/disc ratio ≥ 0.5) and pale only if both observers agreed. ONH imaging was offered to all children but was physically difficult for most. The pediatric neurologist (VV) determined age of onset of POSE clinically and reviewed the available neuroimaging. Results: 43% of the children with POSE had large cups and 33% had pallor. Large cups were seen in 55% of children with neurologic insult (POSE onset) ≤ 28 weeks of gestation (n=11) and 39% with onset > 28 weeks (n=31) (p=0.4). In children with hemiplegic (n=11), diplegic (n=7), quadriplegic (n=21) and miscellaneous (n=3) CP, large cups were found in 18%, 57%, 52% and 33% respectively (p=0.2) and ONH pallor in 9%, 14%, 52% and 33% respectively (p=0.06). In children who were ambulatory (n=24), and non-ambulatory (n=18), large cups were found in 29% and 61% respectively (p=0.04) and ONH pallor in 13% and 61% respectively (p=0.001). Brain CT/MRI was reviewed in 20/42 children. All children with large cups and/or pallor had white matter changes in the posterior periventricular region at the level of the atrium. Conclusions: ONH cupping and pallor is common in POSE. ONH cupping and pallor in POSE is not associated with age of onset as previously hypothesized, but is associated with more severe forms of CP (diplegic and quadriplegic), more severe motor disability (non-ambulatory status) and changes on neuroimaging in the posterior periventricular region. ONH changes in POSE may reflect global CNS pathology manifested by major motor disability and seen as white matter changes on neuroimaging. Diagnosis of CP and determination of the severity of disability is difficult in infancy; children with large cups and/or disc pallor without glaucoma should be referred to pediatric neurologists for evaluation and neuro-imaging. CR: S. kedar, None; D. Ghate, None; V. Vedanarayanan, None; N. Mungan, None; J.J. Corbett, None; C.J. Chen, None. Support: None Purpose: To compare the ability of the multifocal electroretinogram (mfERG) and frequencydomain optical coherence tomography (fdOCT) to detect retinal abnormalities. Methods: Between Oct. 2007 and Nov. 2008, 61 patients (9 to 79 years of age) were referred for mfERG and fdOCT testing to rule out or confirm a retinal etiology of visual loss. Patients were evaluated with mfERG (103 scaled hexagons, VERIS, EDI) and fdOCT (optic disc circular, macula 3D and horizontal line scans, 3DOCT-1000, Topcon). Amplitude and latency changes of the mfERG responses, known to indicate outer retinal abnormalities, were analyzed. The fdOCT scans were examined for changes in the outer retina (RPE, receptor and/or inner nuclear layers). Local regions of abnormal mfERG or fdOCT were compared to local regions of visual field sensitivity loss measured with static automated perimetry (24-2 Humphrey, Zeiss). The mfERG results were categorized as: 1. Normal (normal amplitude and latency); 2. Abnormal (abnormal amplitude and latency consistent with the visual field defect); or 3. Inconclusive (subtle changes or local changes that did not topographically agree with the visual field defect). The fdOCT results were categorized as: 1. Normal (normal outer retina); 2. Abnormal (abnormal outer retina consistent with the visual field defect); or 3. Inconclusive (see above). Results: A total of 35 eyes (24 patients) were categorized as having an abnormal outer retina based upon either the mfERG or fdOCT. Eighteen of these 35 eyes (13 patients) were abnormal on both mfERG and fdOCT. Twelve eyes (8 patients) had an abnormal mfERG, but a normal fdOCT scan. Five eyes (5 patients) had an abnormal fdOCT scan, but a normal (2 eyes/2 patients) or inconclusive (3 eyes/3 patients) mfERG. The group of 16 patients with abnormal mfERG and normal fdOCT included cone-rod dystrophy, AZOOR, vascular damage, agerelated macular degeneration and acute idiopathic blind spot enlargement, while the group of 5 patients with abnormal fdOCT and normal mfERG included local foveal problems (4 patients) and local vascular damage (1). Further, a retinal etiology could not be confirmed in the remaining 37 patients due to normal mfERG and fdOCT results and/or results that did not agree with visual field defects. Conclusions: Although the mfERG and fdOCT results typically agree, some retinal abnormalities are more easily detected in the mfERG, while others may be more apparent on fdOCT. Examination of the cases in which there were clear mfERG changes, but subtle fdOCT changes, improved our ability to detect abnormalities with fdOCT scans. CR: E.A. Dale, None; K.Y. Kay, None; J.G. Odel, None; V. Greenstein, None; D.C. Hood, Topcon, Inc, C. Support: NIH Grant RO1-EY02115, NIH Grant R01-EY-09076 Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4029-4032 Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204 415. Neuro-Ophthalmology Organizing Section: EY 4033 - A195 Comparison of Histologic Change in Lacrimal and Salivary Glands to 67GaCitrate Scintigraphy and T1 Gadolinium Enhanced MRI Findings in Sarcoid Suspects 4034 - A196 Referrals for Suspicion of Optic Neuropathy: Analysis of Diagnostic Pitfalls and Costs Incurred B.J. Frankfort, N.R. Miller. Ophthalmology, Wilmer Eye Institute, Baltimore, MD. H.J. Kim1A, D. Chu1A, L. Frohman1A, N. Mirani1B, R.E. Turbin1A. AOphthalmology, B Pathology, 1UMDNJ-New Jersey Med School, Newark, NJ. Purpose: To correlate lacrimal gland (LGB) and oral (labial) minor salivary gland (SGB) biopsy findings in patients who have gallium or gadolinium uptake of the lacrimal glands (LG) and parotid glands (PG)performed to rule out sarcoid. Methods: Retrospective chart review of consecutive patients (1/2003-11/2008) undergoing LGB and SGB. Inclusion criteria: available preoperative 67Ga-citrate scintigraphy (gallium) scan and/or MRI, and biopsy of LG and/or SG biopsy. Gallium uptake (LG, PG) and MRI (LG, PG) size were each graded into 4 categories. Histology was graded into 4 categories based on degree of inflammation, with the highest grade being granulomatous inflammation. Results: Forty-six patients (31 women, 15 men, average age 39) had both gallium and MRI scans in 25 cases, gallium alone in 19, and MRI alone in 2. Gallium scans showed increased LG uptake in 42, parotid uptake in 35, and submandibular uptake in 4. MRI showed abnormal LG in 8 cases and abnormal parotid in 7 cases. Granulomatous inflammation was seen in 11 cases (4 in both LG and SG, 5 in LG only, 2 in SG only). 8 granulomatous LGs had associated gallium scans that showed intense uptake in 4, moderate in 3, and mild uptake in 1. 12 of 13 patients with severe grade gallium abnormality (LG or PG) had no higher than mild grade biopsy results (SGB or LGB), and 1 had moderate grade inflammation (SGB or LGB). MRI findings in granulomatous LGs were moderate in 1 case, mild in 2, and normal in 1. Granulomatous inflammation in SG had intense PG gallium uptake in 3, moderate uptake in 1 and mild in 1, and had severe abnormalities on MRI in 1, and normal MRI in 2. Conclusions: 67Ga-citrate scintigraphy (gallium) scan and MRI are sensitive in identifying inflammatory reaction but less specific for identifying granulomatous change in LG and in SG. Surgeons may consider SG biopsy in conjunction with LG biopsy as SG may have diagnostic value even when the imaging and LG biopsy are unremarkable. Ultimately, sarcoidosis is a clinical diagnosis and LG and SG biopsies remain a useful confirmatory test. CR: H.J. Kim, None; D. Chu, None; L. Frohman, None; N. Mirani, None; R.E. Turbin, None. Support: Research to Prevent Blindness, Inc, NY; Lions Eye Research Foundation of NJ Purpose: a. Identify ophthalmologic conditions commonly misdiagnosed as an optic neuropathy and the confusing clinical features that may lead to incorrect suspicion. b. Characterize the extent of the clinical workup typically performed for these patients. c. Quantify the financial costs of evaluation for optic neuropathy. Methods: Large consecutive case series, single examiner. Results: Optic Neuropathy is a potentially devastating disorder that may occur in isolation or as a manifestation of a systemic disease. When a diagnosis of optic neuropathy is made or suspicion is considerable, prompt neuro-ophthalmologic evaluation is often warranted. However, the diagnosis of optic neuropathy can be complex, which may lead to referral even in situations where the diagnosis of optic neuropathy is suspect. As the workup for optic neuropathy can be extensive, referral for optic neuropathy often is accompanied by a significant financial burden. Furthermore, the implications of neurologic ocular involvement can be emotionally devastating to a patient. Therefore, it is in our best interest to ensure that referral for optic neuropathy occurs primarily in settings of the highest suspicion. To achieve this, diagnoses commonly mistaken for optic neuropathy should be identified. We have performed a retrospective analysis of 102 consecutive patients seen by a single neuro-ophthalmologist at the Wilmer Eye Institute from 20022008 who were referred for suspicion of optic neuropathy but did not, in fact, have the disease. Patients had an average age of 60.8 (SD = 15.9), were mostly female (71%), and were predominantly Caucasian (87%). Referral sources included general ophthalmologists, ophthalmic subspecialists, optometrists, internists, neurologists and neurosurgeons. Visual acuity, presence of a relative afferent pupillary defect, color vision, and optic nerve findings were highly variable. The vast majority of patients (>80%) had undergone prior visual field testing, and most patients had undergone prior neuroimaging (MRI or CT). Anterior segment pathology (including refractive error) and retinal pathology each accounted for 28% of referrals. Glaucoma accounted for an additional 18% of referrals. Surprisingly, 21% of patients had a normal eye examination. Incurred diagnostic costs were substantial. Conclusions: Common ophthalmic diseases are frequently mistaken for an optic neuropathy. Such diagnostic errors by the referring physician suggest either a lack of understanding of the characteristics of an optic neuropathy or a concern that the physician is “missing something” and may lead to both unnecessary emotional burden for the patient and a significant cost to the health care system. CR: B.J. Frankfort, None; N.R. Miller, None. Support: None 4035 - A197 Clinical Polymorphism of Myasthenia Gravis Beginning With Isolated Ocular Symptoms 4036 - A198 NMR-Based Metabolomic Analysis of Cerebrospinal Fluid and Serum in Neuro-Ophthalmological and Neurological Diseases - A Diagnostic Tool? J. Boumendil1, C. Vignal-Clermont2, J. Allali1, J.-L. Dufier1, S. Morax2. 1Necker, paris, France; 2Rothschild’s ophthalmologic foundation, paris, France. A.J. Sinclair1A,1B, M.R. Viant1C, G.R. Wallace1A, A.K. Ball1D, M.A. Burdon1A, E.A. Walker1B, P.M. Stewart1B, S.P. Young1E, S. Rauz1A. AAcademic Unit of Ophthalmology, School of Immunity, Infection and Inflammation, BEndocrinology, School of Experimental Medicine, CSchool of Biosciences, DNeurology, School of Experimental Medicine, E Rheumatology, School of Immunity, Infection and Inflammation, 1University of Birmingham, Birmingham, United Kingdom. Purpose: the aim of this study is to highlight the clinical diversity of myasthenia gravis beginning with isolated ocular symptoms. Methods: we present a 15 patients series that we have been taking care of at Rothschild’s Ophthalmologic Foundation from 2002 to 2007. Every patients have been examinated by the same ophthalmologist for isolated ocular symptoms. An acetylcholin-receptor antibodies research, a cerebral RMI and a chest tomography have been systematically realized. Results: When the disease was diagnosed, 11 patients out of 15 had a ptosis with a diplopia, 2 had an isolated ptosis and 2 had an isolated diplopia. After investigations, we discovered that three patients had a malignant thymoma and one had a thymic hyperplasia. An autoimmune disease association has been found with 2 patients: the first one had a Hashimoto’s thyroiditis and the second one has developed an optical neuro-myelitis few years after his myasthenia gravis. Only three patients secondarily developed a generalized myasthenia gravis. This could be explained by the early attending of these patients, and the common prescription of an immunosuppressive therapy reducing the risk of secondarily generalised myasthenia gravis according to some studies. Conclusions: Despite the small number of patients, this study well underlines the clinical polymorphism of ocular myasthenia gravis, the risks it may cause, and the important role of the ophthalmologists in the diagnosis of this disease. Close collaboration between ophthalmologists and neurologists is needed to ensure a well taking care of these patients. CR: J. Boumendil, None; C. Vignal-Clermont, None; J. Allali, None; J.-L. Dufier, None; S. Morax, None. Support: None Purpose: Establishing biomarkers for conditions affecting the central nervous system have to date proven to be problematic. Processes such as gene transcription, and environmental factors, can affect the metabolic fingerprint of tissues. The recent innovation of metabolomic analysis of biofluids has the capacity to integrate these bio-influences into a single biomarker profile. We therefore sought to define whether metabolomic biomarker profiling of cerebrospinal fluid (CSF) and serum could potentially distinguish between idiopathic intracranial hypertension (IIH), multiple sclerosis (MS) and cerebrovascular disease (CVD) from patients with mixed neurological diseases. Methods: Spectra of CSF (n=87) and serum (n=72) were acquired using 1H NMR spectroscopy. Multivariate pattern recognition analysis was used to identify disease specific metabolite biomarker profiles. The metabolite profiles were then used to predict the diagnosis of a prospectively collected cohort of patients (n=25). Results: CSF metabolite profiles were able to predict diagnosis with a sensitivity and specificity of 80% for both IIH and for MS. The CVD serum metabolite profile was 75% sensitive and specific. On analysing the second prospective patient cohort, the established metabolite biomarker profiles generated from the first cohort showed moderate ability to segregate patients with IIH and MS (sensitivity: specificity of 63%:75% and 67%:75%, respectively). Conclusions: These findings suggest that NMR spectroscopic metabolic profiling of CSF and serum can identify differences between IIH, MS, CVD and mixed neurological diseases. Metabolomics may, therefore, have the potential to be developed into a clinically useful diagnostic tool. The identification of disease-unique metabolites may also impart information on disease pathology. CR: A.J. Sinclair, None; M.R. Viant, None; G.R. Wallace, None; A.K. Ball, None; M.A. Burdon, None; E.A. Walker, None; P.M. Stewart, None; S.P. Young, None; S. Rauz, None. Support: Alex Sinclair is a Medical Research Council Clinical Research Training Fellow (UK) and the Academic Unit of Ophthalmology is supported by the Birmingham Eye Foundation (Registered (UK) Charity 257549) Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4033-4036 Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204 415. Neuro-Ophthalmology Organizing Section: EY 4037 - A199 Dry Eye, Blinking, and Hemifacial Spasm 4038 - A200 Inter-Observer Variability of Hertel Exophthalmometry Stratified by Training Experience I.S. Kassem1, C. Evinger2, H. Pomeranz1. 1Department of Ophthalmology, North Shore-Long Island Jewish, Great Neck, NY; 2Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY. B.A. Karwoski, F.A. Killian, C. Rosenberg, Y.P. Glavas. Ophthalmology, New York University, New York, NY. Purpose: Hemifacial spasm (HFS) is a disorder characterized by involuntary facial muscle spasms that begin in one eyelid and progress to the ipsilateral lower facial muscles. Eyelid spasms result from closely spaced bursts of orbicularis oculi (OO) muscle activity that resemble blink oscillations with an extremely short interblink interval. The primary cause of HFS is unilateral pulsatile arterial compression of the facial nerve at the root entry zone. This pressure causes facial nerve weakness, resulting in poor tear film production that initiates an adaptive increase in the blink reflex. We investigated the effect of increased cornea afferent activity on the eyeblink and the incidence of eye irritation in HFS patients. Methods: To investigate the effect of reduced tear production, four male spraguedawley rats had surgical implantation SO nerve stimulation electrodes and OO electromyogram (EMG) recording electrodes. Rats were tested for several days prior to surgical removal of the exorbital lacrimal gland. We reduced cornea afferent activity in two dry eye model rats by anesthetizing the cornea with tetracaine. We also recorded OOEMG activity of two normal human subjects and increased cornea afferent activity using a simultaneous air puff and reflex blink stimulus. To investigate if eye irritation is more prevalent in HFS patients, we performed a retrospective chart review of 36 HFS patients and compared the incidence of their eye complaints with age-matched controls. Results: Lacrimal gland removal in rats resulted in blink oscillations accompanying innocuous reflex blink stimuli without any change in reflex blink threshold, blink amplitude, or trigeminal excitability. Reducing cornea afferent activity in these rats with corneal anesthetic reduced the probability of oscillations evoked by reflex blinks. In normal human subjects, increasing cornea afferent activity by pairing the reflex stimulus with an air puff increased the probability of blink oscillations. HFS patients also had more complaints of eye irritation compared to control patients. Conclusions: Cornea irritation initiates the production of multiple blinks to a normally single blink-evoking cutaneous trigeminal stimulus. These blink oscillations may occur because of coincident cutaneous and elevated cornea afferent activity. The spasms of lid closure in HFS might be an exaggeration of these multiple blinks closely spaced together in time. Together, these studies show that eyelid spasm disorders such as HFS may be due in part to a disruption in the adaptation to cornea drying and irritation. CR: I.S. Kassem, None; C. Evinger, None; H. Pomeranz, None. Support: EY07391 (CE) and NS4467301 (IK). Purpose: To investigate the inter-observer variability and accuracy of Hertel exophthalmometry and analyze whether it is a learned clinical skill improved through repetition and experience. Methods: In this comparative study, simultaneous bilateral Hertel exophthalmometry was performed on four different patients in consecutive fashion by 36 ophthalmologists stratified by training level experience (residents, oculoplastics fellows, and neuro-ophthalmology and oculoplastics attendings). The patients had no history of orbital disease and were of different genders and ethnic backgrounds. Each observer was blinded and three measurements were taken for each patient using a Marco Prism Exophthalmometer (Marco Instrument Co, Jacksonville, Florida, USA). Additionally, each resident completed a brief survey evaluating their formal education and exposure to exophthalmometry. Results: The PGY-2 residents demonstrated the greatest variation for globe position and intercanthal distance, respectively (PGY-2: 6mm and 20mm; PGY-3: 5mm and 13mm; PGY-4: 3.5mm and 8mm). The subspecialty attendings (gold standard) showed the least variation for globe position at 2mm. There was no statistical difference for accuracy of measurements for globe position between each level of training (ANOVA analysis p = 0.336). The difference in accuracy for intercanthal distance between the PGY-2 residents and all other groups was statistically significant (PGY-3: p = 0.032; PGY-4: p = 0.008; Attg: p = 0.011). The difference in accuracies for intercanthal distance between PGY-3 and PGY-4 and each with the attendings were not statistically significant. Finally, 59% of residents had formal clinical training, 6% had didactic training and 76% felt it was a useful clinical skill. Conclusion: The inter-observer variability for axial globe positioning and intercanthal distance is inversely correlated with training experience. The accuracy for globe positioning in exophthalmometry did not correlate with training level. However, the accuracy for intercanthal distance did correlate with training level. It appears that more senior residents improve the placement of the exophthalmometer footplates over the temporal margin of the lateral orbital rim. Secondly, the survey showed that almost half the residents felt they did not have adequate clinical training on how to perform exophthalmometry but support its clinical utility. In summary, evaluating the anteroposterior position of the globe within the orbit is not a learned skill but is felt to be clinically relevant and valuable. New emphasis on exophthalmometry training may be warranted to improve our evaluation and management of orbital disease. CR: B.A. Karwoski, None; F.A. Killian, None; C. Rosenberg, None; Y.P. Glavas, None. Support: None 4039 - A201 Prognosis and Riskprofile of Patients With Aniridia 4040 - A202 Choroidal Effusion: An Important Hallmark in Carotid-cavernous Fistula. Report on 2 Cases E. Gramer1, C. Reiter1, G. Gramer2. 1Department of Ophthalmology, University Wuerzburg, Wuerzburg, Germany; 2Hospital for Pediatric and Adolescent Medicine, University Heidelberg, Heidelberg, Germany. M.G. Todorova, A.M. Palmowski-Wolfe, J. Messerli, P. Meyer. Ophthalmology, University of Basel Eye Clinic, Basel, Switzerland. Aniridia is a panocular eye malformation caused by heterozygous mutations within PAX6 gene, a paired-box transcription factor, or cytogenetic deletions of chromosome 11p13 that encompass PAX6. PAX6 has a wide expression in the developing eye, in the neuroectoderm and the surface ectoderm and therefore in their derivates, lens, cornea and retina. Purpose: To evaluate in patients with aniridia: 1)Frequency of congenital cataract, lens dislocation, nystagmus, corneal opacification, poor foveal development, family history of aniridia. 2)Frequency of glaucoma (GL) or ocular hypertension (OH) and maximum intraocular pressure (IOP max). 3)Visual acuity prognosis. Methods: Retrospective analysis of ophthalmologic, paediatric and internal findings in 30 consecutively examined patients with aniridia and photo documentation. Age of the patient at first clinical examination, family history and IOP max were requested. Results: 1)Mean age at first clinical examination in 30 patients with bilateral aniridia (17 male, 13 female)was 28±19,3 years (range 2 month-62 years). Age distribution at first clinical examination: up to 9 years: 23,3%, 10-19: 13,3%, 20-29: 13,3%, 30-39: 10%, 40-49: 26,7%, 50-59: 3,3%, 60-69: 6,7%. Congenital cataract had 76,7% (23 of 30 patients), in 20 patients bilateral, in 3 unilateral. 5 patients (16,7%) had bilateral dislocation of the crystalline lens upwards. 8 had corneal opacifications, 3 unilateral, 5 bilateral. One patient had poor foveal development, one patient (3,3%) had a Wilms´ Tumor. 2 patients (6,7%)had optic nerve hypoplasia. 53,3% presented nystagmus. Family history of aniridia was found in 10 patients (33,3%) with 1-4 relatives. 2) Frequency of glaucoma was 66,7% (20 patients), 10% unilateral, 90% bilateral. Mean IOP max of 20 glaucoma patients was 35,9 mmHg in the right and 32,6 mmHg in the left eye. 3)A decreased visual acuity in the better eye of 20/100 or less was found in 60% of all patients. Conclusions: Inspite of pseudophakia patients with aniridia had severely decreased visual acuity related to nystagmus, glaucomatous damage and as a result of the other associated various ocular abnormalities. Elevated IOP occurs very infrequently in childhood. Buphthalmus was only found in one patient. Most commonly IOP starts to increase not before adolescence. Schlemm´s canal may be absent in many patients. Due to a highly variable expression of aniridia in relatives a thorough examination of family members is required to provide early diagnosis, amblyopia prophylaxis and a correct genetic counceiling. CR: E. Gramer, None; C. Reiter, None; G. Gramer, None. Support: None Purpose: Indirect fistulas are usually low-flow fistulas with a reduced arterial blood flow. Retrograde venous drainage through the cavernous sinus into to the superior ophthalmic vein (SOV) is less pronounced than in high-flow fistulas. As a consequence, there is less bruit on auscultation, which makes the diagnosis difficult. Associated findings such as choroidal effusion, which may lead to a shallow anterior chamber and an elevated IOP, are considered to be rare complications. Methods: We report on two patients, where the ultrasound biomicroscopic (UBM) demonstration of choroidal effusion was paramount in diagnosing an indirect carotidcavernous fistula (CCF). The patients underwent ophthalmological examination including a 50 Hz UBM (Paradigm Medical Industries, Inc, P60TM) to examine the choroidea, the anterior chamber depth and the anterior chamber angle. Results: The 1st patient, a 56-year-old man, presented with chemosis, episcleral injection and proptosis of the right eye (4mm). A diagnostic MRI had been read as consistant with SOV thrombosis, EOP or pseudotumor orbitae. A follow up examination revealed a new shallow anterior chamber OD with a normal IOP of 17mmHg. UBM confirmed the reduced anterior chamber depth of 2.5mm (norm: 2.7mm) and demonstrated annular cilio-choroidal effusion with edema of the ciliary body. An angle closure was suggested by an anterior chamber angle of <20° in all four quadrants, namely 13.8° @12h, 12.2° @3h, 12.7° @6h, 19.3° @9h. This effusion lead to the suspected diagnosis of an indirect CFF which could be confirmed on MRA.The 2nd patient, a 62-year-old man, presented with episcleral injection and proptosis of the right eye (3.5mm). Doppler sonography showed a prominent SOV. Neuroimaging revealed an indirect CCF from an AV-malformation in the cavernous sinus. A followup one week after therapeutic embolisation of the fistula revealed a shallow anterior chamber OD, IOP: 21mm. UBM confirmed worsening of the clinical situation with a chamber depth of 1.86 mm, a closed chamber angle of 7.33° @3h, 7.17° @9h, 0 @12h & 6h, secondary to annular cilio-choroidal effusion, which lead to a pseudo-plateau configuration of the iris. Conclusions: Angle-closure secondary to annular cilio-choroidal effusion was found in both patients with indirect CCFs. UBS seems to be an useful non-invasive diagnostic tool to aid in diagnosis and follow-up of patients with indirect CCF. We suggest, that more widespread use of UBM might reveal choroidal effusion in more patients with low flow fistulas and thus help in early diagnosis of this disorder. CR: M.G. Todorova, None; A.M. Palmowski-Wolfe, None; J. Messerli, None; P. Meyer, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4037-4040 Wednesday, May 6, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 4017 - 4042 / A179 - A204 415. Neuro-Ophthalmology Organizing Section: EY 4041 - A203 Dizziness: Simple Clinical Test Battery To Evaluate Hyperstimulation Syndromes J. Ilson1, K.J. Ciuffreda2. 1Ophthalmology, E S Harkness Eye Institute, New York, NY; 2 Vision Sciences, SUNY College of Optometry, New York, NY. Purpose: It is well known that some individuals without apparent neurological disease are hypersensitive to motion, especially in the peripheral visual fields. Furthermore, many patients with head trauma, stroke, and even migraine exhibit a similar but more exaggerated heightened response. We sought to develop simple, inexpensive procedures to reproduce these phenomena in a clinical setting Methods: We examined 20 symptomatic patients/subjects and 15 asymptomatic subjects using a rapidly moving OKN drum, repeated convergence to near-point, proprioceptive neck vibration, with a total test time of less than five minutes. Results: All previously symptomatic subjects experienced their stereotypic hypersensitivity to all of the above whereas asymptomatic controls did not exhibit a similar response. The stereotypic hypersensitivity response included disorientation, panic, nausea, a variety of visual phenomena (diplopia, visual tilt, visual avoidance of complex patterns), dizziness and/or gait ataxia sometimes lasting several hours. Conclusion: Using this simple test battery with patients, we were able to reproduce consistently their real-life symptoms. This even applies to those with unremarkable neurological, ophthalmological, and vestibular examinations and in some cases with normal neuro-imaging. Our findings may have diagnostic and therapeutic as well as medical-legal ramifications. CR: J. Ilson, None; K.J. Ciuffreda, None. Support: None 4042 - A204 Migrainous Visual Aura Due to Focal Cerebral Lesions. Can the Diagnosis Be Made on the Semiology of Attacks? Nine Case Reports and Review of the Literature P.N. Shams1,2, G.T. Plant1,2. 1Ophthalmology, Moorfields Eye Hospital, London, United Kingdom; 2Neuro-ophthalmology, The National Hospital for Neurology and Neurosurgery, London, United Kingdom. Purpose: To identify clinical features which could differentiate between the visual auras of idiopathic migraine and those due to structural cortical lesions which also fulfill the diagnostic criteria for idiopathic migraine with visual aura, as defined by The International Classification of Headache Disorders. Methods: Prospective observational study including nine cases of migraine-like visual aura due to focal cerebral lesions seen in the practice of one neuro-ophthalmologist at Moorfields Eye Hospital and The National Hospital for Neurology and Neurosurgery London between 1986 and 2008. A further 31 cases from the literature were identified by searches of PubMed from 1966 until March 2008. Results: Five key clinical features are outlined in detail to help to identify which patients with migraine-like visual auras require further investigation; 1) Onset of visual aura for the first time in fourth or fifth decade of life; 2) Duration of the visual aura less than 5 minutes; 3) Increase in frequency or change in the pattern of longstanding visual auras; 4) Visual auras recurring in the same location in the visual field; 5) Unexplained visual field defect (VFD) and/or persistent VFD following a typical visual aura. Conclusions: Photopsia and the slow propagation of scintillating scotoma across the visual field are strongly associated with the visual aura of idiopathic migraine. Our cases support the observation that visual auras fulfilling the diagnostic criteria for idiopathic migraine, can arise from acquired cortical lesions. Despite the considerable overlap in the characteristics of visual aura caused by migraine, epilepsy and structural cerebral lesions, certain features can help to differentiate between these conditions in order to identify patients who require further investigation. We hypothesize that the co-morbidity and overlap in clinical features of these chronic neurological disorders is due to a common underlying pathophysiology; namely a state of neuronal hyperexcitability. Whether due to genetic predisposition or acquired through brain injury, neuronal hyperexcitability increases an individuals’ susceptibility to the generation of cortical spreading depression, the electrophysiological correlate of the visual aura in migraine. CR: P.N. Shams, None; G.T. Plant, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4041-4042 Wednesday, May 6, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 4696 - 4712 / D962 - D978 460. Amblyopia I Organizing Section: EY 4696 - D962 Post-Operative Grating Acuity Outcomes in Children With Down Syndrome and Bilateral Cataracts 4697 - D963 How Does One Define Success in Amblyopia Treatment? G.E. Quinn1, B.M. Melia2, Pediatric Eye Disease Investigator Group. 1Pediatric Ophthalmology, Childrens Hospital of Philadelphia, Philadelphia, PA; 2Jaeb Center for Health Research Foundation, Tampa, FL. S.R. Salomao, A. Berezovsky, P.Y. Sacai, J.M. Pereira, N.N. Cavascan, M.B. Tartarella. Dept of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil. Purpose: Down syndrome is the most commonly identified genetic form of developmental disability with an estimated incidence of 1:600 live births in Brazil. Cataract occurs in 1.5-20% of Down syndrome cases, mainly bilaterally, leading to severe visual impairment if not treated. The purpose of this study is to investigate grating acuity outcomes in children with Down Syndrome undergoing cataract extraction. Methods: Best-corrected grating acuity (BCGA) was measured electrophysiologically by sweep visual evoked potential (sweep-VEP) technique from each eye in 13 patients with Down Syndrome (age 6 months - 10 years; 6 females) who had been operated for bilateral cataracts (11 aphakic - 22 eyes, 2 pseudophakic - 3 eyes). An additional group of 10 patients with Down Syndrome and absence of cataract in each eye was also tested (age 2 months - 12 yrs; 3 females). Acuity deficits from mean normal were calculated based on age norms from our own lab. Amblyopia was diagnosed when interocular acuity difference > 0.1 logMAR was detected. Results: Age at surgery ranged from 1.5 to 60 months of age (mean=13.4±12.9; median=9). BCGA was measured within 3 months - 8 years after surgery (mean=24.3±33.6 mos.; median=7.2 mos). In cataract-operated patients, BCGA deficits were present in all eyes (0.13 - 1.36 logMAR; mean=0.61±0.31; median=0.50), with amblyopia in 7 (53.8%) patients. Patients with Down Syndrome without cataract showed BCGA deficit in 13(65.0%) eyes (0.08 - 0.79 logMAR; mean=0.37±0.25; median=0.27) and none had amblyopia. Greater acuity deficits were found in cataract-operated eyes compared with eyes from patients with Down Syndrome and no cataract (Mann-Whitney rank sum test, P=0.023). Conclusions: Post-operative grating acuity outcomes in Down syndrome patients with bilateral cataracts disclosed substantial deficits as well as high frequency of amblyopia. Better acuity outcomes could probably be achieved with earlier diagnosis and surgical treatment, providing improved visual function and quality of life for these patients. CR: S.R. Salomao, None; A. Berezovsky, None; P.Y. Sacai, None; J.M. Pereira, None; N.N. Cavascan, None; M.B. Tartarella, None. Support: None Purpose: To compare definitions used to determine outcome in studies of amblyopia treatment Methods: Using data from completed amblyopia clinical trials conducted by the Pediatric Eye Disease Investigator Group to develop a statistical model, we simulated visual acuity data for clinical trials of treatment for moderate amblyopia over a range of ages and treatment effects and compared type I and II error rates for 8 different definitions of treatment success that have been used or proposed as outcome measures for treatment studies of amblyopia. Results: Of the continuous outcome measures considered (lines improved, proportion of deficit corrected (PDC), and intraocular difference (IOD)), lines improved had good statistical properties across the range of scenarios studied. Both PDC and IOD had high chance of type I error when the treatment could adversely affect sound eye acuity. Of the dichotomous outcomes considered (better than 20/25, better than 20/32, improved 2 or more lines, equal vision in both eyes, and better than 20/32 or improved 3 or more lines), improved 2 or more lines generally had the best statistical power. Like PDC and IOD, the equal visual acuity outcome had high type I error when the treatment could adversely affect sound eye visual acuity. In general, given a fixed sample size, continuous outcomes had greater power to detect treatment differences than the dichotomous outcomes. Conclusions: Choice of an outcome should be based on biological plausibility, clinical relevance, and safety, as well as statistical properties that maximize the chances of detecting a treatment difference and minimize chances of coming to an erroneous conclusion. Either continuous or dichotomous outcome measures may be reasonable choices for a primary outcome measure for clinical trials of amblyopia treatment. The outcomes of lines improved and improvement of 2 or more lines of visual acuity had good statistical properties across a wide range of conditions likely to be encountered in studies of amblyopia treatment, although other choices of outcome may perform well under specific circumstances. IOD and equal visual acuity had poor statistical properties in most circumstances and should not generally be used as primary outcome measures. CR: G.E. Quinn, None; B.M. Melia, None. Support: National Eye Institute EY011751 4698 - D964 Macular Thickness and Retinal Nerve Fiber Layer Thickness Measurements in Amblyopic and Normal Eyes of Children Using Spectral Domain OCT 4699 - D965 Macular Thickness in Amblyopic Eyes With Myopic Anisometropia P.H. Kok1A, Y.C. Besselink1B, R. De Kinkelder1C,2, J. Kalkman1C, M.E.J. Van Velthoven1A, F.D. Verbraak1A. AOphthalmology, BOrthoptics, CBiomedical Engineering and Physics, 1Academic Med Ctr Amsterdam, Amsterdam, Netherlands; 2Topcon Europe Medical BV, Capelle a/d IJssel, Netherlands. Purpose: The purpose of this study was to investigate the macular thickness and retinal nerve fiber layer (RNFL) thickness, in relation to the axial length (AL) in amblyopic and normal eyes of children, using spectral domain OCT (SD-OCT). Methods: Included amblyopic and healthy children underwent full ophthalmic and orthoptic examination, volume scanning of the macula and optic disc with SD-OCT (32 b-scans consisting of 512 a-scans, 3D OCT-1000,Topcon) and recording of AL using the IOL master (Zeiss Meditec). The foveal and pericentral retinal thicknesses (RT) and peripapillary RNFL thickness were then calculated using a custom built Matlab (The MathWorks, Inc.) based program. Results: Twenty-four amblyopic patients (14 boys and 10 girls, mean age 7.7 ± 1.9) and 25 healthy children (11 boys and 14 girls, mean age 8.1 ± 1.5) were enrolled in this study. Except for four amblyopic children, a negative correlation was found between the AL and RT (r=0.44 p<.05). After excluding these four patients, in the remaining group of 20 children both the amblyopic and fellow eyes were significant shorter and had thicker pericentral RT compared to control eyes (see Table). No differences were found in the other parameters between the three groups. AL was a significant covariate (p<.01), whereas age and gender were not. After correcting for AL, no significant differences were found between the three groups for all parameters. Using paired testing amblyopic eyes were 0.3 ± 0.4 mm shorter than their fellow eyes, however they did not have significantly different RT and RNFL thickness measurements. Conclusions: In 20 amblyopic children in our study, the thicker pericentral RT as compared to healthy controls seems to be explained by the shorter AL. However, in four amblyopic children an inverse correlation between AL and RT was found. Further research will focus on this finding. CR: P.H. Kok, None; Y.C. Besselink, None; R. De Kinkelder, Topcon Europe Medical BV, E; J. Kalkman, None; M.E.J. Van Velthoven, None; F.D. Verbraak, None. Support: None Y. Pang, G. Goodfellow, C. Allison, S. Block, K.A. Frantz. Illinois Coll of Optom, Chicago, IL. Purpose: To compare macular thickness of the sound eye to that of the amblyopic eye using optical coherence tomography (OCT) in patients with myopic anisometropia. The associations between macular thickness, axial length and refractive error in the amblyopic eyes were also investigated. Methods: 24 subjects (17 females and 7 males) with a mean age of 10.6 yrs (5 to 25 yrs) were recruited. Macular thickness, A-scan, visual acuity, and cycloplegic refraction were measured on the amblyopic and sound eye. Macular thickness of both eyes was compared (paired t-test). Partial correlations were used to test the relationships among macular thickness, axial length and refractive error in amblyopic eyes while controlling for age and sex. Results: Mean ± SD spherical equivalent in amblyopic eyes was -11.33 ± 3.16 diopters (D) with a range of -5.25 to -17.50 D and -2.10 ± 3.12 D in sound eyes. The mean magnitude of anisometropia was 9.23 ± 3.71 D, ranging from 3.63 to 17.50 D. Mean axial length was 26.87 ± 1.68 mm in amblyopic eyes and 23.46 ± 1.40 mm in sound eyes. Macular thickness is shown in Table 1. A significant difference in macular thickness was found between amblyopic and sound eyes. No correlation was found between macular thickness and axial length or macular thickness and refractive error in amblyopic eyes. Conclusions: Histopathological studies have shown retinal thinning with myopia. Retinal involvement in amblyopia is controversial with some studies reporting a thicker macula in the amblyopic eye. We believe this is the first study to measure macular thickness in amblyopic eyes associated with myopia. Amblyopic eyes with high myopia had significantly thicker minimum and average foveas but thinner inner and outer maculae compared to sound eyes. Macular thickness in the amblyopic eyes was not related to axial length or refractive error. CR: Y. Pang, None; G. Goodfellow, None; C. Allison, None; S. Block, None; K.A. Frantz, None. Support: Illinois Society for the Prevention of Blindness, CIBA Vision, and Illinois College of Optometry Faculty Research Fund Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4696-4699 Wednesday, May 6, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 4696 - 4712 / D962 - D978 460. Amblyopia I Organizing Section: EY 4700 - D966 The Pupil in Suppression and Amblyopia E.P. Herlihy1, S.M. Archer2. 1Pediatric Ophthalmology, Seattle Children’s Hospital, Seattle, WA; 2Pediatric Ophthalmology, University of Michigan Kellogg Eye Center, Ann Arbor, MI. 4701 - D967 The Prevalence of Amblyopia and it Relationship With the Child’s Diagnosis and Age: The Iowa KidSight Vision Screening Experience A. Leon, S.Q. Longmuir, R.J. Olson, W. Pfeifer, B. Zimmerman, W.E. Scott. Dept of Ophthalmology, University of Iowa, Iowa City, IA. Purpose: To test the hypothesis that the apparent afferent pupillary defect that has been reported in amblyopic eyes is due to lack of fixation by the eye with poorer vision, and to determine if there is a magnitude of pupillary asymmetry that cannot be attributed to lack of fixation in amblyopia. Methods: Ten volunteers with equal best corrected visual acuity in each eye and a normal eye exam were recruited. A twenty prism diopter base down prism was placed over the right eye, and the subject was instructed to fixate on a distant target and suppress the displaced image. Pupillary reactions were assessed with the swinging flashlight test. Asymmetric responses were quantified using neutral density filters. Results: Asymmetric pupillary responses were observed in seven of the ten subjects (70%) with equal visual acuity and normal eye exams when the subjects were instructed to maintain fixation with the eye without the prism [video clip]. Pupillary reactions equalized with a 0.3 log unit neutral density filter held over the eye without the prism in six of the seven subjects (86%). The pupillary asymmetry reversed in one of the seven subjects (14%) with the 0.3 log unit filter. Conclusions: Lack of fixation caused an apparent afferent papillary defect in seven of ten normal subjects without amblyopia. Thus, there is no need to postulate a failure of development of retinal ganglion cells in amblyopes. However, no pupillary asymmetry resulting from lack of fixation measured greater than 0.3 log units in our study. Any larger asymmetric response warrants further investigation for optic nerve disease. CR: E.P. Herlihy, None; S.M. Archer, None. Support: None Purpose: Vision screening programs allow early detection of children with or at risk for amblyopia. We analyzed the effect of child’s diagnosis and age on the prevalence of amblyopia in children screened by Iowa KidSight Vision Screening Program. Methods: Database from Iowa KidSight Vision Screening Program was used to identify children referred to an eye specialist. The diagnosis from eye specialist, presence of amblyopia, and child’s age were recorded and analyzed with logistic regression analysis. Results: From May 1, 2000 to April 30, 2007, 2680 children were referred for an eye specialist evaluation. Follow-up information was available for 1981 children. Of these, 731 children were found to have amblyopia. After performing our statistical analysis we found significant interaction between diagnosis and age (p=0.02). We analyzed the effect of age on all diagnosis types and found only statistically significant increase of prevalence in amblyopia in the children with anisometropia (p=0.002) with increased age. Conclusions: Among the different diagnosis groups, anisometropia was the only diagnosis group in which the prevalence of amblyopia increased significantly with age. Vision screening technologies have allowed earlier detection of this condition. Strategies for early treatment for anisometropic children could lead to prevention or early treatment of amblyopia. Continued efforts in early detection of this condition could lead to better outcomes. CR: A. Leon, None; S.Q. Longmuir, None; R.J. Olson, None; W. Pfeifer, None; B. Zimmerman, None; W.E. Scott, None. Support: RPB, Lions Clubs of Iowa, Lions Club International Foundation 4702 - D968 Naso-Temporal Asymmetry of Retinal Function in Children With Strabismic Amblyopia 4703 - D969 Experience-Dependent Plasticity of Form and Motion Mechanisms in Human Amblyopia F. Campagna1, B. Falsini2, G. Carnovale Scalzo1, V. Scorcia1, G. Scorcia1, C. Russo1, M. Rechichi1, A. Paola1, G. Scorcia1, D. Bruzzichessi1. 1Ophthalmology, Magna Graecia University, Catanzaro, Italy; 2Institut of Ophthalmology, Catholic University, Rome, Italy. S.I. Chen1,2, A. Chandna 3, M.W. Pettet4, A.M. Norcia4. 1Ophthalmology, The Galway Clinic, Galway, Ireland; 2Ophthalmology, University of Liverpool, Liverpool, United Kingdom; 3Ophthalmology, The Royal Liverpool Children’s Hospital, Liverpool, United Kingdom; 4Infant Vision Lab, The Smith-Kettlewell Eye Research Institute, San Francisco, CA. Purpose: Previous studies¹ have shown naso-temporal asymmetry of spatial interaction in strabismic amblyopia. The aim of this study was to compare nasotemporal hemiretinal function with pattern electroretinogram (PERG) in children with strabismic amblyopia. Methods: Ten children with a diagnosis of strabismic amblyopia (3 males, 7 females, mean age: 6 ± 1 years), with a visual acuity of 0.4-0.7 in the amblyopic and of 1.0 Snellen units in the fellow eye were analyzed. All patients had convergent strabismus ≥ 10 prismatic dioptres (D). All children were hyperopic and four were astigmatic > 1.5 D. Pattern electroretinogram (PERG) was recorded in response to transient stimuli generated on a 19” TV monitor (temporal frequency 2 Hz, check size 30’), presented to the central retinal region (22 x 22 degrees) and to nasal and temporal hemiretinal fields. Analysis was according to ISCEV guidelines. Results: In the amblyopic eyes, the central PERG was significantly reduced in mean amplitude (p < 0.01) compared to the fellow eyes. However, nasal hemiretinal amplitude losses were significantly greater than corresponding temporal losses ( - 23.2 ± 4 % versus - 4.5 ± 5.6 %, p < 0.01). Conclusions: Strabismic amblyopia shows a retinal dysfunction characterized by a naso-temporal asymmetry, suggesting a retinal genesis of the reduction of nasal hemiretinal input to the visual cortex. CR: F. Campagna, None; B. Falsini, None; G. Carnovale Scalzo, None; V. Scorcia, None; G. Scorcia, None; C. Russo, None; M. Rechichi, None; A. Paola, None; G. Scorcia, None; D. Bruzzichessi, None. Support: None Purpose: Deprivation of patterned visual input during early visual development leads to both anatomical and functional losses in the deprived eye. Disagreement exists (human literature) as to whether the non-deprived eye shows super-normal behavior. Here we use spectral analysis of Visual Evoked Potential (VEP) responses to isolate relative position and motion/transient responses in previously untreated children who experienced deprivation of high-spatial frequency input in one eye due to chronic optical defocus (anisometropia). Methods: Normal children (n=16) and previously untreated amblyopes (n=12) under eight years old were studied longitudinally during clinical treatment. VEP responses to a 3.76Hz Vernier displacement stimulus were subjected to spectral analysis. Positional responses (first harmonic) and motion/transient responses (second harmonic) were the main outcome measures compared before and after occlusion therapy. Results: Position-specific responses are super-normal in the non-deprived eye and markedly subnormal in the deprived eye prior to treatment. Motion/transient responses, on the other hand show no difference from normal in the non-deprived eye and milder losses in the deprived eye. After occlusion of the initially deprived eye, the position signal decreased in the initially non-deprived eye and increased in the initially deprived eye. No measurable effect of occlusion occurred for the motion/ transient response. Conclusions: These results suggest that position and motion/transient signals arise from separate mechanisms with very different sensitivity to optical deprivation and conversely, to reversal of the deprivation effect by occlusion therapy. CR: S.I. Chen, None; A. Chandna, None; M.W. Pettet, None; A.M. Norcia, None. Support: EY06579, OR2001-99a. CT: If Other, enter the registry site and corresponding number Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4700-4703 Wednesday, May 6, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 4696 - 4712 / D962 - D978 460. Amblyopia I Organizing Section: EY 4704 - D970 Comparison of the Accommodative Response in Amblyopic and NonAmblyopic Eyes 4705 - D971 The Role of Autorefraction in Addition to Visual Acuity Testing, Questionnaires and Inspection in Preschool Vision Screening at 3.5 Years in Japan C. Rook1, D. Oystreck1, S.E. Loudon2, D.G. Hunter1. 1Ophthalmology, Children’s Hospital, Boston, MA; 2Ophthalmology, Erasmus University, Rotterdam, Netherlands. Purpose: Accommodative dysfunction has previously been reported in amblyopic eyes. Most studies were performed in a non-clinical setting, using few subjects and no children. In this study, a prospective, case control design was used to assess the accommodative ability of amblyopic children. Methods: Two clinical tests of accommodation were used to compare the amblyopic eye with the sound eye and in age matched controls: 1) WAM 5500 binocular accommodation autorefractor, and 2) dynamic retinoscopy. The accommodative response to a 3 diopter stimulus was assessed under binocular and monocular viewing conditions. Results: To date, 37 amblyopic and 24 control subjects (mean age 7.8 years) have been tested. Accommodative response was normal in 49% of amblyopic eyes, 70% of sound eyes, and 76% of non-amblyopic control eyes under binocular viewing conditions. Accommodative response was normal in 51% of amblyopic eyes, 62% of sound eyes, and 70% of non-amblyopic control eyes under monocular viewing conditions. Dynamic retinoscopy was normal in 84% of amblyopic eyes, 92% of sound eyes, and 100% of non-amblyopic control eyes. Conclusions: When tested with an objective, quantitative method, amblyopic eyes appeared to have a reduced accommodative response under both binocular and monocular viewing conditions. Sound eyes in amblyopia patients performed as well as non-amblyopic eyes in controls. The reduced accommodative response in amblyopic eyes may have implications in the treatment of amblyopia as well as in amblyopia screening. Enrollment of more patients and controls will be needed to provide sufficient power for meaningful statistical analysis. CR: C. Rook, None; D. Oystreck, None; S.E. Loudon, None; D.G. Hunter, None. Support: Research to Prevent Blindness Walt and Lilly Disney Award 4706 - D972 Benefits of Electrodiagnostic Testing (EDT) in the Assessment of Amblyopia in Children With Congenital Ptosis and Its Correlation With Orthoptic Findings Y.H. Luo1A,2, A. Liasis2,3, B. Walters2, Y.A. Abou-Rayyah2,1B. AOphthalmology, BAdnexal Service, 1Moorfields Eye Hospital, London, United Kingdom; 2Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital, London, United Kingdom; 3The Ulverscroft Vision Research Group, Institute of Child Health, London, United Kingdom. Purpose: To determine the benefit of EDT in the management of congenital ptosis in children Methods: A retrospective comparative case series of 33 patients with congenital ptosis who attended a tertiary paediatric oculoplastics centre. Patients with other ocular / neurological conditions which compromised vision were excluded. As part of their investigations patients underwent both electrodiagnostic (EDT) and orthopitc testing. The results were compared to look for similarities and discrepancies on patient cooperation with each assessment modality, the outcomes of the assessments, and the management decisions based on the assessments. Results: In 41 out of 70 episodes (59%), both EDT and orthoptic were in agreement to the presence or absence of amblyopia and as a result management decision was based on both assessments. In a number of cases only either EDT or orthoptic testing could be achieved and as a result management was based on the successful modality (3 separate episodes each for EDT and orthopitic testing). Of interest the EDT and orthoptic findings were in disagreement in 23 patient episodes. In these cases management was based on orthoptic findings in 18 episodes while on EDT findings in the remaining 5 episodes. Conclusions: EDT was found to be beneficial in attaining monocular visual assessment in all the children patients. It did not alter clinical management in children able to carry out subjective recognition acuity tasks or in those older than 15 months of age, as subjective recognition acuity testing is considered the gold standard for monocular visual assessment on which management is based. In situations when EDT and orthoptic findings contradict each other, other clinical factors (e.g. extent of ptosis, compliance of occlusion therapy) should be taken into consideration in the decision making. In older patients who are able to perform subjective recognition visual acuity, orthoptic assessments alone may be adequate in monitoring their visual function. We recommend to perform both EDT and orthoptic assessments in patients under 15 months of age, to maximise the detection of amblyopia and allow early institution of appropriate treatment. CR: Y.H. Luo, None; A. Liasis, None; B. Walters, None; Y.A. Abou-Rayyah, None. Support: None C. Matsuo1, T. Matsuo2, K. Kio3, N. Ichiba 3, H. Matsuoka 3. 1Orthodontist, Kyoyama Dental Center, Okayama City, Japan; 2Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama City, Japan; 3Okayama City Government Health Care Office, Okayama City, Japan. Purpose: Children at 3.5 years in Japan undergo physical, mental and developmental checkup, based on Maternal and Childhood Health Law since 1961. Vision and hearing examinations were included since 1991. The vision-screening program consists of 3 steps: questionnaires and home visual acuity testing as 1st step, visual acuity testing by nurses and inspection by medical officers at regional Health Care Centers as 2nd step, and detailed examinations by ophthalmologists as 3rd step. In this study, we conducted hand-held autorefraction in addition to visual acuity testing and inspection at regional Heath Care Center to reveal whether autorefraction leads to better detection of eye problems. Methods: Hand-held autorefraction was done by a single well-trained examiner (C.M.) in 265 children at 3.5 years who visited at Okayama East Health Care Center in 6 consecutive sessions from Nov 2007 to Feb 2008. As the current standard, eyes were inspected by medical officers, and visual acuity tests using 0.1 and 0.5 Landolt-C cards at 5 m for each eye were done by nurses in children who failed or did not undergo visual acuity testing at home. Children were sent to 3rd step examinations by ophthalmologists, based on refractive error criteria: >3 diopters myopia, >2 diopters astigmatism, or >1 diopter hyperopia in either eye, in addition to the current criteria: 1) failure in either eye for 0.5 visual acuity, 2) eye-related symptoms raised by questionnaires, or 3) eye problems detected by medical officers. Results: Notice to visit ophthalmologists was issued for 64 children (24%), and 37 of those (58%) did so to make documents wiith final diagnoses sent back to Health Care Office. Of the 64 children, 12 was sent to ophthalmologists based on the current criteria only, 9 based on both the current criteria and the refractive error criteria, and 43 based on the refractive error criteria only. Eleven of 12 children visiting ophthalmologists by the current criteria had diagnoses such as amblyopia and strabismus. In contrast, 16 of 25 children visiting ophthalmologists by the refractive error criteria only had mainly diagnoses of refractive errors with no serious problems. Conclusions: Autorefraction in addition to visual acuity testing and inspection led to additional eye disease detection at 3.5 years. Autorefraction is not recommended as an additional test from the viewpoint of cost-effectiveness as far as the current system was conducted appropriately. CR: C. Matsuo, None; T. Matsuo, None; K. Kio, None; N. Ichiba, None; H. Matsuoka, None. Support: Special Budget Allocation for Community-Oriented Research from Okayama University in 2007 4707 - D973 Neural Correlates of Pattern Perception in Human Amblyopia: An MEG Study Z.A. Hirji1A, F. Cortese1A, H.C. Goltz1A, D.O. Cheyne1B, A.M. Wong1A. AOphthalmology and Vision Sciences, BDiagnostic Imaging, 1The Hospital for Sick Children, Toronto, ON, Canada. Purpose: The neural basis of amblyopia remains elusive: there is contradictory evidence on whether visual deficits result primarily from dysfunction of early visual cortex (V1/V2) or extrastriate cortex. In this study, we investigated the roles of early and late visual cortical areas and their interactions in human amblyopes by using magnetoencephalography (MEG). Methods: Prior to MEG recording, 2 adult amblyopes and 6 visually normal subjects performed a behavioural experiment in which subjects detected static Glass patterns (radial or rotational) monocularly. The signal strength (% of correlated dot-pairs) of the Glass patterns was varied to determine the level at which the subject perceived the pattern 80% of the time. During MEG recording, the signal strength of the Glass pattern was set at the previously measured 80% performance level so that the amblyopic and fellow eyes in patients with amblyopia and healthy eyes in normal controls were stimulated equally across subjects and stimulus conditions. Results: Behaviorally, Glass pattern perception by the amblyopic eyes produced slower response times and required higher signal strengths when compared to the fellow and healthy eyes. Using beamformer-based spatial filtering, brain activity maps revealed bilateral activation in early visual areas (V1/V2) shortly after visual presentation for both amblyopic and normal subjects. However, ~250 ms after visual presentation, stimulation of the amblyopic eye produced attenuated activity in the extrastriate lateral occipital complex (LOC) bilaterally, and different activity in the right inferior parietal area, when compared to the fellow and healthy eyes. In addition, time course analysis of the source waveforms at these brain locations revealed a different pattern of interaction between early and later visual areas when stimulating the amblyopic eye, than was observed for fellow and healthy eyes. Conclusions: The neural basis of amblyopia may be related to an abnormal interaction between early visual (V1/V2) and extrastriate cortices. CR: Z.A. Hirji, None; F. Cortese, None; H.C. Goltz, None; D.O. Cheyne, None; A.M. Wong, None. Support: Canadian Foundation for Innovation, Canadian National Institute for the Blind Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4704-4707 Wednesday, May 6, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 4696 - 4712 / D962 - D978 460. Amblyopia I Organizing Section: EY 4708 - D974 Patten Visual Evoked Potential (P-VEP) in Adult Monocular Amblyopia 4709 - D975 EPSC Changes After CSPG Degradation in Rat Visual Cortex During Visual Critical Period S.-K. Moon, K. Lim. Department of Ophthalmology, School of Medicine, Ewha Womans University, Mok-dong Hospital, Seoul, Republic of Korea. Z.Q. Yin, C. Wang. Southwest Eye Hospital, Southwest Hospital, Chongqing, China. Purpose: To investigate the clinical guideline of pattern visual evoked potential (P-VEP) parameters as the diagnostic criteria for adult monocular amblyopia Methods: From Jan 2000 to May 2008, medical charts of patients who visited for medical certificates for the military service were reviewed. Any suspicious malingering patients or bilateral amblyopic patients were excluded. Only patients who has definite causes of amblyopia or whose amblyopia has been confirmed on the childhood medical record were included in the study group. Normal subjects who have best-corrected visual acuity more than 20/20 were selected as the control group. The P100 latency and amplitude were compared between the amblyopic eye and the normal control group. The P100 latency and amplitude ratios were calculated from both eyes and were compared between the amblyopic group and the normal control group. Results: Eighty-two charts of patients were reviewed. Sixty-seven patients were included in this study. Forty-seven patients were monocular amblyopic group and 20 patients were normal control group. Of the 47 monocular amblyopic patients, 32 had anisometropic amblyopia, 4 had strabismic, 3 had visual deprivation, and 8 had idopathic amblyopia. The P100 latency of monocular amblyopic eye was 118.69±27.02msec, which was significantly delayed than that of normal subjects, 103.62±5.45msec. The P100 amplitude of monocular amblyopic eye was 5.89±3.23μV, which was significantly decreased than that of normal subjects, 8.84±4.57μV. The P100 latency ratio of monocular amblyopic group was 1.18±0.32, which was significantly higher than that of normal subjects, 1.03±0.02. The P100 amplitude ratio of monocular amblyopic group was 0.65±0.36, which was significantly lower than that of normal subjects, 0.77±0.15. All patients with P100 latency ratio more than 1.10 had monocular amblyopia. All patients with P100 amplitude ratio less than 0.47 had monocular amblyopia. 21(44.7%) out of 47 monocular amblyopic patients showed P100 latency ratio within 2 SD of the normal control group. 30(63.8%) out of 47 monocular amblyopic patients showed P100 amplitude ratio within 2 SD of the normal control group. Conclusions: The P100 latency ratio more than 1.10 or the P100 amplitude ratio less than 0.47 can be used as the diagnostic criteria of adult monocular amblyopia. Although some patients with monocular amblyopia showed normal P-VEP parameters, P-VEP could be employed usefully as a diagnostic tool for adult monocular amblyopia. The clinical correlation is mandatory to diagnose adult monocular amblyopia. CR: S.-K. Moon, None; K. Lim, None. Support: None Purpose: For the treatment of amblyopia is closely related with critical period of visual plasticity which terminative mechanism was unknown. The relationship between chondroitin sulphate proteoglycan (CSPG) and synaptic events during the critical period of the visual cortex was studied. CSPG, an extracellular matrix component condenses around neurons to form perineuronal nets (PNNs) encapsulating the cell, and may be a mechanism that ends the critical period of visual plasticity. Methods: Recordings from normal rat (Long Evens) visual cortex between postnatal week 3 (P3W) to P8W were compared with those from rats after chondroitinase ABC (chABC) injections to degrade CSPG. Whole-cell patch-clamping was used to record glutamatergic excitatory postsynaptic currents (Glu-EPSCs), and NMDA and AMPA receptor mediated EPSCs from layers II - IV in tissue slices of the visual cortex. Results: 1: EPSCs were recorded from 33/58 neurons in the normal visual cortex. There were no significant changes in NMDA-EPSCs amplitude (pA) (P > 0.05) between P3W to P8W. AMPA-EPSC amplitude steadily increased between P3W and P7W (P6W-P8W vs P3W, P < 0.05) coinciding with the closure of the rat’s visual critical period. NMDA/ Glu EPSC amplitude ratios gradually decreased between P3w - P6W, concomitant with an increase in AMPA/Glu EPSC amplitude ratios. 2: Neurons (31/51) were isolated and recorded after CSPG degradation following chABC injections 7 days before recording. There was a significant and steady increase in NMDA-EPSC amplitudes until P7W (P < 0.05 vs P3W). AMPA-EPSCs amplitudes similarly increased, albeit not as significantly. After chABC NMDA/Glu EPSC amplitude ratios were consistently higher than in normal animals, whereas the AMPA/Glu EPSC amplitude ratios were consistently lower. Conclusions: The PNNs formed with CSPG appear to be correlated with a decrease in of NMDA-EPSC amplitudes in rat visual cortex between P4W - P8W. CSPG may preferentially inhibit of NMDA transmission and synaptic plasticity as development proceeds by shifting the balance towards more AMPA/Glu receptor sites, thus, ending the visual critical period. CR: Z.Q. Yin, None; C. Wang, None. Support: Chinese NSFC grant # 30672280 4710 - D976 Effect of a Combined Patching and Atropine Treatment in Patients With Anisometropic Amblyopia With Microtropia for the Prevention of Amblyopia Recurrence 4711 - D977 How Dutch Orthoptists Handle Non-Compliance With Occlusion Therapy for Amblyopia F. Matsumoto1, A. Yamabe1, H. Yamamoto1, Y. Nakao1, A. Wakayama2, Y. Shimomura2. 1 Ophthalmology, Kinki Univ Sch of Medicine,Sakai-Hospital, Sakai, Japan; 2 Ophthalmology, Kinki Univ Sch of Medicine, Osaka-sayama, Japan. Purpose: We have previously reported that anisomertopic amblyopia with microtropia often recurs after a patching treatment. To prevent the recurrence, we investigated the effect of a combined patching and atropine occlusion treatment in patients with anisometropic amblyopia with microtropia. Methods: Eight patients (mean age, 69±10 months) with anisometropic amblyopia with microtropia were included. The mean refractive errors for the amblyopic and fellow eyes were +5.69±1.11D and +2.15±1.5D (spherical), respectively. Patient’s pretreatment visual acuity (VA) of the amblyopic eye ranged from 0.30-1.04 logMAR. The treatment protocol was as follows: (1) an initial patching time of eight hours or longer per day was set, (2) the patching time was reduced to 3-5 hours per day depending to the patient’s age when the VA ceiling of the amblyopic eye was reached, (3) if VA of the amblyopic eye remained stable, treatment of 1% atropine eye drops once per day was started on the fellow eye. During a follow-up period of 6-72 months, recurrence of amblyopia was determined based on the VA stability of the amblyopic eye. Results: Seven (87.5%) of the eight patients, had improved VA of 0 logMAR in the amblyopic eye after the patching treatment and were able to maintain their VA after the atropine occlusion treatment. The other patient (12.5%) had improved VA of 0.15 logMAR after the patching treatment and the VA was further improved after the atropine occlusion treatment. The overall treatment required 8-17 months; and the respective means were 5.14 months for the patching treatment of 8 hours or longer per day, 2 months for the patching treatment of 3-5 hours per day, and 3.14 months for the atropine occlusion treatment. None of the patients experienced amblyopia recurrence during the follow-up period. Conclusions: Because atropine occlusion promotes binocular rivalry under binocular condition, an atropine occlusion treatment following patching can effectively prevent recurrence of amblyopia. CR: F. Matsumoto, None; A. Yamabe, None; H. Yamamoto, None; Y. Nakao, None; A. Wakayama, None; Y. Shimomura, None. Support: None A.M. Tjiam1A, E. Vukovic1A, W.L. Asjes-Tydeman1B, M.M. Sinoo2, S.E. Loudon1A, H.J. Simonsz1A, J.R. Polling1A. AOphthalmology, BPublic Health, 1Erasmus Medical Center, Rotterdam, Netherlands; 2Orthoptics, Utrecht University, Utrecht, Netherlands. Purpose Non-compliance causes treatment failure in occlusion therapy for amblyopia. Predictors of low compliance are low initial visual acuity, a low parental fluency in Dutch, a low level of education, and country of origin (IOVS 2006; 47: 4393-400). We examined how Dutch orthoptists handle non-compliance with occlusion therapy in general and sought for differences related to the risk factors. Methods A structured questionnaire was sent to all Dutch orthoptists. Nine orthoptists in low-SES areas (group A) and 23 orthoptists dispersed over the Netherlands (group B) were studied in more detail with a semi-structured interview, structured questionnaires and direct, non-participated observations. Patients’ demographic characteristics, organizational structure of the clinic, attendance-rates, concept of non-compliance, awareness of non-compliance, attitude towards non-compliance, approach towards non-compliance and communication with parent and child were evaluated. In children living in low-SES areas compliance was measured electronically. Results Mean age of patients of B-orthoptists was 4.2 ± 1.1 years and A-orthoptists 4.6 ± 1.2 years. Patients of B-orthoptists had less than moderate fluency in Dutch in 4.6% and A-orthoptists in 36.9%. Patients of A-orthoptists were Dutch in 33.9%, Surinamese in 7.5%, Moroccan in 21.8% and Turkish in 13.2%. The electronic measurements of the compliance showed that approx. 48% of the children occluded less than 50% of the prescribed occlusion time; 16.7% did not occlude at all. One-hundred-and-seventy-four of all Dutch orthoptists (58%), who answered the structured questionnaire, estimated their patients’ compliance to be 72.7%, on average. The A and B-orthoptists estimated their patient’ compliance to be 66% and 75.5%, respectively. Patients of A-orthoptists did not show up at appointments in 9.6% and B-orthoptists in 6%. None of the B-orthoptists and four of the nine A-orthoptists found themselves inadequate in dealing with non-compliance. A-orthoptists gave 2’30” explanation about diagnosis and treatment to parents and B-orthoptists 4’21”. All orthoptists did not communicate with the child during their explanation. Conclusion Orthoptists underestimated the size of poor compliance with occlusion therapy. Despite differences in fluency in Dutch, explanation of A-orthoptists is shorter, which is caused by a shorter allotted time for a patients’ first visit (21’ versus 27’24”). CR: A.M. Tjiam, None; E. Vukovic, None; W.L. Asjes-Tydeman, None; M.M. Sinoo, None; S.E. Loudon, None; H.J. Simonsz, None; J.R. Polling, None. Support: ZonMw The Netherlands organisation for health research and development #6320.0008 CT: www.trialregister.nl/trialreg/index.asp Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4708-4711 Wednesday, May 6, 1:45 PM - 3:30 PM Hall B/C Poster Session Program Number/Board # Range: 4696 - 4712 / D962 - D978 460. Amblyopia I Organizing Section: EY 4712 - D978 Can Orthoptically Trained Personnel Carry Out Preschool Screening in the Absence of an Orthoptist? L. North, M.F.P. Griffiths, G. Menon. Frimley Park Hospital Foundation Trust, Frimley, United Kingdom. Purpose: To determine the number of false positive and false negative referrals made to a Hospital Eye Service from a Community Vision Screening service carried out by Health Visitors Methods: A retrospective cross sectional study was carried out from January 2000- January 2002. Data was obtained from patient records of 126 children referred to the Princess Mary’s Hospital, MOD Cyprus, who were booked to see either the Ophthalmologist &/or the Orthoptist. Health visitors under went training in 2001 with the visiting orthoptist in order to carry out a pre-school visual screening service. Standards of testing and referral guidelines were issued for them to follow and further data was collected to determine the number and % of children referred that were true and false positives, source of referral, age of the child at referral, time lapse between referral and ophthalmic appointment, reason for referral, whether standards of testing were followed. A convenience sample was then taken from the children that had been previously tested by the health visitor during 2001 and re tested by the orthoptist to determine the number of false negative results. Factors that were also examined included, method of assessment, assessment outcome, general logistics for examination, equipment used and age of child at testing. Results: Prior to the introduction of the new direct referral system to the ophthalmic service at The Princess Mary’s Hospital, MOD, Cyprus 41% were false positive. This shows a high percentage of the total referrals made were unnecesssary.Following the training of health visitors in pre-school visual assessment, 54% of the direct referrals made by the health visitor proved to be false positive. In spite of this high false postive referral rate, 8 out of 34 children that had been classified as normal were found to be false negative on retest by the orthoptist. 4 children were found to have bilateral reduced vision, 2 had manifest squints, 1 child was found to have a significant esophoria and a further child failed the 20 dioptre prism test. All required referral to the ophthalmologist. Conclusions: This study provides considerable support to the recommendations that orthoptists should carry out pre-school visual screening services.Despite training and a higher false positive referral rate, the number of false negatives is a concern and could be indicative of an even higher number prior to training.The effectiveness of orthoptists in the detection of visual defects remains to be the most acceptable method of assessment of pre-school children but further evaluation needs to carried out in order to provide a service when there is not a permanent orthoptist. Is some screening better than none? CR: L. North, None; M.F.P. Griffiths, None; G. Menon, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4712 Wednesday, May 6, 3:45 PM - 5:30 PM Palm A Paper Session Program Number Range: 4749 - 4755 463. Amblyopia II Organizing Section: EY 4749 - 3:45PM Amblyopia in Children with Cranial Nerve Palsies Secondary to Brain Tumors M.E. Hoehn1A, M.L. Bratton1B, N.C. Kerr1A. AOphthalmology, BCollege of Medicine, 1 Univ of Tennessee Health Sci Ctr, Memphis, TN. Purpose: Early onset visual pathology tends to be more amblyogenic. We evaluated the relationship between age of onset for cranial nerve palsies (CNP) and the development of amblyopia. Methods: We performed a retrospective chart review of 73 children diagnosed with a CNP (III, IV, or VI) associated with a brain tumor who did not have any other ophthalmic diagnoses which would impact visual acuity. Results: Twenty children developed amblyopia (Group A) and had a mean age of 2.8 years at time of CNP diagnosis (range = 0.42 - 9.75 years, SD 2.3). Fifty-three children did not develop amblyopia (Group B) and had a mean age of 7.9 years at time of CNP diagnosis (range = 0.83 - 17.6 years, SD 4.6). The age at diagnosis was significantly different between the two groups (p < 0.0001). Amblyopia developed in 67% of children age 0-2 years at CNP diagnosis, in 50% at 2-4 years, in 18% at 4-6 years, in 9% at 6-8 years, and in 4% over 8 years. There was no significant difference between the two groups with respect to tumor type, treatment, or motility and strabismus resolution (overall 47% and 11%, respectively). Conclusions: Children with CNP from brain tumors may be particularly susceptible to amblyopia, as the strabismus from the CNP does not usually resolve. The likelihood of amblyopia in young children suggests a role for more aggressive and/or prophylactic amblyopia therapy in children under 4 years of age who develop CNP. Younger children who develop CNP secondary to brain tumors are at high risk for developing amblyopia. CR: M.E. Hoehn, None; M.L. Bratton, None; N.C. Kerr, None. Support: None 4751 - 4:15PM Treatment of Amblyopia Using Macular Stimulation With Telescopic Magnification 4750 - 4:00PM Electrophysiological Detection of Delayed Post-Retinal Neural Conduction in Amblyopia E.C. Campos1, M.E. Scarale1, N. Balducci1, M. Fresina1, V. Parisi2. 1Ophthalmology Unit, University of Bologna, Bologna, Italy; 2GB Bietti Foundation, IRCCS, Roma, Italy. Purpose: Simultaneous recordings of pattern electroretinograms (PERG) and visual evoked potentials (VEP) allow us to separate a macular dysfunction from a delay in neural conduction along post-retinal visual pathaways1. Our work aims to evaluate the macular function and the neural conduction along the visual pathways in amblyopic patients. Methods: 25 anisometropic amblyopic patients [mean age 7± 1.9 years; Visual Acuity (VA): 0.44± 0.27 LogMAR in amblyopic eyes (AE), 0.023± 0.067 LogMAR in sound eyes (SE)] and 25 age-similar controls (AS eyes, VA of 0.0± 0.0 LogMAR in both eyes) were enrolled. In AE, SE and AS eyes, simultaneous PERG and VEP were recorded in response to checks reversed at the rate of 2 reversals/s stimulating macular or extramacular areas (the checks edge subtended 15’ and 60’of visual arc respectively) 2 . Results: Non significant differences (ANOVA, p>0.01) in PERG and 60’ VEP responses and in 60’ Retinocortical Time (RCT; difference between VEP P100 and PERG P50 implicit times) between AE, SE and AS eyes were observed. AE eyes showed a significant (p<0.01) increase in 15’ VEP P100 implicit time and in 15’ RCT with respect to the values observed in SE and AS. In amblyopic patients the interocular difference in VA was significantly (Pearson’s Test, p<0.01) related to the interocular difference in 15’ VEP P100 latencies and in 15’ RCT. Conclusions: Our amblyopic eyes showed abnormal visual cortical responses only when the macular area is stimulated (increase in 15’ VEP P100 implicit times). This functional impairment, in presence of a normal macular function (15’ PERG responses similar to control ones), can be ascribed to a delay in post-retinal neural conduction (increase in 15’ RCT). The interocular differences in post-retinal neural conduction were correlated to the interocular differences in visual acuity. 1 Celesia GG, Kaufman D, IOVS, 1985;26:726-35. 2 Tomoda H, Celesia GG, Toleikis SC. Electroencephalogr Clin Neurophysiol 1990;80:8188. CR: E.C. Campos, None; M.E. Scarale, None; N. Balducci, None; M. Fresina, None; V. Parisi, None. Support: This work was supported in part through a grant from the Fondazione Cassa di Risparmio in Bologna 4752 - 4:30PM Natural History of Anisometropia and Its Association With Amblyopia A.M. Wong, J. Wu, F. Nazemi, J. Schofield. Ophthalmology, Hospital for Sick Children, Toronto, ON, Canada. Purpose: A recent study (Nazami et al, 2008) suggested that telescopic magnification improves visual acuity (VA) in older children with anisometropic amblyopia who have failed previous treatment; however, a proper control group was lacking. The present study aims to evaluate the effects of telescopic magnification on amblyopic patients, and compare their results with those without telescope treatment. Methods: Amblyopic patients, aged 4-17, who have failed previous treatment were recruited. Inclusion criteria were: (1) VA 20/40-20/400 in the amblyopic eye; (2) VA 20/40 or better in the sound eye; (3) intraocular VA difference of at least 0.3 logMAR; and (4) absence of any ocular pathology. Patients were randomly assigned to either 30 minutes of patching of the sound eye only daily (patching only group), or 30 minutes of patching of sound eye plus concurrent use of a telescope (2.2x) on the amblyopic eye daily (telescope group). Using a ETDRS logMAR chart, best corrected VA was recorded at baseline and at 5 weeks after treatment. Results: Thirteen patients were recruited. Seven patients were assigned to the patching only group, and six to the telescope group. The mean baseline VA of patients in the two treatment groups was similar (0.8 logMAR). There was no significant difference in mean VA improvement between the telescope (0.22 logMAR) group and patching only group (0.25 logMAR; p=0.69). Conclusion: Treatment of refractory amblyopia in children using telescopic magnification does not appear to be effective. Ongoing recruitment of more patients and longer followup at 17 weeks would further clarify the effectiveness of this treatment. CR: A.M. Wong, None; J. Wu, None; F. Nazemi, None; J. Schofield, None. Support: Hospital for Sick Children Jack Crawford Fund CT: If Other, enter the registry site and corresponding number S.H. Sharbini1A, K.A. Rose1A, G. Burlutsky1B, P. Mitchell1B, Sydney Childhood Eye Study. ADiscipline of Orthoptics, BCentre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, 1University of Sydney, Sydney, Australia. Purpose: To examine the natural history of anisometropia and its association with amblyopia in a population-based random cluster sample of 6- and 12-year-old students. Methods: The Sydney Myopia Study randomly selected 55 primary and secondary schools, stratified by socio-economic status (SES); 4069 children (70% response rate) were examined. Cycloplegic autorefraction, LogMAR visual acuity, cover tests (cover/ uncover alternate, prism bar) at near and distance were performed. Anisometropia was defined by the spherical equivalent [SE = spherical refraction + (0.5 X cylindrical refraction)] and an astigmatic cylinder (AST) difference between the right and left eye of >1.0 dioptre. Amblyopia was defined as best corrected visual acuity in the worse eye less than 6/12 Snellen equivalent and/or a two line difference between the two eyes. Cases included those present at time of examination, as well as those reported by parents, and confirmed by a history of occlusion therapy. Results: Anisometropia was present in 3.8% (n = 155) of the population and of these 31.4% were amblyopic. There was a significant difference in the prevalence of anisometropia in the 6-year-old (2.5%) compared with the 12-year-old (4.7%) children (p = 0.0002). There were more amblyopic cases in the 6-year-olds (41.9%) than the 12-yearolds (27.9%).The number of amblyopic cases significantly increased with increasing degrees of anisometropia in 1.0D steps >1.0D (23.7%), >2.0D (46.7%), >3.0D (66.7%) and >4.0D (80.0%) (p < 0.0001).There was a marked increase in cases of amblyopia when astigmatic refraction increased from 2.0D to 3.0D (10.8% to 50.0%, respectively), a trend that continued with increasing refractive difference (p < 0.0001). The most frequent type of anismometropia was myopic anismoetropia (46.8%) and the least common was astigmatic anisometropia (21.2%). Conclusions: Our study showed that the prevalence of anisometropia was higher in the older than the younger group. 1D difference of anisometropia significantly increased the risk of developing amblyopia. Astigmatic anisometropia degree of 3Ds seemed to show a marked increase in the number of amblyopic cases. CR: S.H. Sharbini, None; K.A. Rose, None; G. Burlutsky, None; P. Mitchell, None. Support: Australian NHRMC grant 253732 Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4749-4752 Wednesday, May 6, 3:45 PM - 5:30 PM Palm A Paper Session Program Number Range: 4749 - 4755 463. Amblyopia II Organizing Section: EY 4753 - 4:45PM Treatment of Severe Amblyopia With Atropine: Results From Two Randomized Clinical Trials 4754 - 5:00PM Massachusetts Preschool Vision Screening Program: Two Year Program Evaluation M.X. Repka1, R.T. Kraker2, R.W. Beck 2, E. Birch 3, S.A. Cotter4, J.M. Holmes5, R.W. Hertle 6, D.L. Hoover7, D.L. Klimek 8, Pediatric Eye Disease Investigator Group. 1Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, MD; 2Jaeb Center for Health Research, Tampa, FL; 3Retina Foundation of the Southwest, Dallas, TX; 4Southern California College of Optometry, Fullerton, CA; 5Ophthalmology, Mayo Clinic, Rochester, MN; 6Ophthalmology, Children’s Hospital of Pittsburgh, Pittsburgh, PA; 7Everett and Hurite Ophthalmic Association, Pittsburgh, PA; 8Children’s Eye Care & Adult Strabismus Surgery, South Charleston, WV. J.E. Ramsey1, B. Moore2, A.H. Sheetz3, T. Comerford 3, L. McIntyre3. 1Ophthalmology, Boston University School of Medicine, Boston, MA; 2New England College of Optometry, Boston, MA; 3Massachusetts Dept of Public Health, Boston, MA. Purpose: To determine the effectiveness of weekend atropine for severe amblyopia from strabismus, anisometropia or both combined among children 3 to 12 years of age. Methods: We enrolled children into two prospective, randomized multi-center clinical trials of amblyopia therapy. Herein we report the results for severe amblyopia, 20/125 to 20/400. In Trial 1, 60 children 3 to 6 years of age (mean age 4.4 years) were randomized to weekend atropine plus a plano lens with weekend atropine with full spectacle correction for the sound eye. In Trial 2, 40 children 7 to 12 years of age (mean age 9.3 years) were randomized to weekend atropine or two hours of daily patching. The visual acuity outcome was assessed at 18 weeks in Trial 1 and 17 weeks in Trial 2. Results: In Trial 1, visual acuity improved by an average of 4.5 lines in the atropine plus correction group (95% confidence interval (CI) 3.2 to 5.8 lines) and 5.1 lines in the atropine plus plano lens group (95% CI 3.7 to 6.4 lines). In Trial 2, visual acuity improved by an average of 1.5 lines in the atropine group (95% CI 0.5 to 2.5 lines) and 1.8 lines in the patching group (95% CI 1.1 to 2.6 lines). Conclusions: Atropine can improve visual acuity in children 3 to 12 years of age with severe amblyopia. Improvement may be greater in younger children. CR: M.X. Repka, None; R.T. Kraker, None; R.W. Beck, None; E. Birch, None; S.A. Cotter, None; J.M. Holmes, None; R.W. Hertle, None; D.L. Hoover, None; D.L. Klimek, None. Support: NIH Grant EY011751 CT: www.clinicaltrials.gov, NCT00315328 Purpose: To evaluate the Massachusetts Preschool Vision Screening Program two years after implementation. Methods: Following a legislative mandate, the Massachusetts Preschool Vision Screening Program was developed, based on a “medical home” model where preschool children receive vision screening by the primary care provider. In addition, the school nurses provided a backup support system. Working in collaboration with the Massachusetts Department of Public Health, an aggressive state-wide educational campaign was developed and targeted to pediatric primary care providers and school nurses. Two years after initiation of the program, a randomized phone survey of 100 primary care pediatric practices was conducted. In addition, a mail survey of pediatric healthcare providers was conducted in both 2005 and 2007. Comparative data was able to be obtained. An on-line survey tool inquiring about both the frequency and quality of vision screening was developed and targeted to school nurses; data was reported for 29,811 preschool children. Additional school nurse information was obtained on nearly 11,000 enrolled kindergarten students from a self-selected cohort of nurse leaders. Results: Ninety nine percent of the primary care physicians contacted in the randomized phone survey indicated that they were aware of the new mandated preschool vision screening program and 89% reported that they were implementing the program. The mail survey from 2007 showed a significant increase in the number of physicians who reported use of the mandated vision screening protocol compared with 2005: picture symbol use declined and HOTV/Lea symbol use increased from 18% to 65%. Stereo testing, part of the recommended protocol, increased from 15% to 85%. 65% reported using recommended methods of ocular occlusion compared with 11% at baseline. Results from the school nurse surveys showed an increase in the number of preschoolers screened by primary care providers, from 44% in 2005 to 62% in 2007. Conclusions: Two years after the Massachusetts Preschool Vision Screening Program was initiated, there has been an increase in both the rates and quality of preschool vision screening. CR: J.E. Ramsey, None; B. Moore, None; A.H. Sheetz, None; T. Comerford, None; L. McIntyre, None. Support: Massachusetts Department of Public Health 4755 - 5:15PM Polarization Modulation Using Wave Plates to Enhance Foveal Fixation Detection in Retinal Birefringence Scanning for Strabismus Screening Purposes K. Irsch1,2, B.I. Gramatikov2, Y.-K. Wu2, D.L. Guyton2. 1Kirchhoff Institute for Physics, University of Heidelberg, Heidelberg, Germany; 2The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD. Purpose: To enhance foveal fixation detection while bypassing the deleterious effects of corneal birefringence in binocular retinal birefringence scanning (RBS) for strabismus screening purposes, a new RBS design was developed incorporating a double-pass spinning half wave plate (HWP) combined with a fixed double-pass wave plate (WP) into the optical system. Methods: The incorporation of the spinning HWP effectively enables differential polarization detection with only one detector, and together with a fixed WP the differential polarization signal can be detected essentially independently of various amounts and orientations of corneal birefringence that occur in the population. Utilizing the measured corneal birefringence from a data set of 300 human eyes, an algorithm and related computer program were developed in MATLAB for optimizing the properties of both wave plates to statistically maximize the foveal fixation signal, while having the greatest independence from left and right eye corneal birefringence. The computer model was verified with experimental human data using an intermediate RBS-based eye fixation monitor. Results: Foveal fixation detection was optimized with the HWP spun 9/16 as fast as the circular scan, with the fixed WP having a retardance of 45° and fast axis at 90°. With this optimized RBS design, a significant statistical improvement of 7.3 times in signal strength, i.e. FFT power, was achieved for the available data set compared with the previous RBS design. Validation experiments confirmed the model’s ability to find the optimum amount of double-pass retardance necessary to yield maximal signal strength for the investigated range of corneal birefringence. Conclusions: The computer-model-optimized RBS design greatly enhances foveal fixation detection. Combining a binocular eye fixation monitor based on this new RBS design with bull’s-eye focus detection promises to be both robust and sensitive in screening infants automatically and reliably for both of the primary causes of amblyopia: strabismus and defocus. CR: K. Irsch, None; B.I. Gramatikov, None; Y.-K. Wu, None; D.L. Guyton, The Johns Hopkins University School of Medicine, P. Support: Robert and Maureen Feduniak, Dewey and Janet Gargiulo, David and Helen Leighton, Richard and Victoria Baks, Robert and Diane Levy, and Research to Prevent Blindness (DLG). Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 4753-4755 Thursday, May 7, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 5344 - 5356 / A295 - A307 517. Optic Neuropathy I Organizing Section: EY 5344 - A295 Bilateral Optic Atrophy: A Background Finding in Cynomolgus Macaques Used in Toxicologic Research 5345 - A296 Immunohistochemical Study of the Receptor for Advanced Glycation End Products in the Microvasculature of Alzheimer’s Optic Nerves R.R. Dubielzig1A, R. Leedle2, T.M. Nork1B, J.A. VerHoeve1B, B.J. Christian2. APathobiol Sciences and CORL, BOphthalmolgy and Visual Sciences and CORL, 1Univ of Wisconsin-Madison, Madison, WI; 2Pathology, Covance Laboratories Inc, Madison, WI. M.Y. Wang, F.N. Ross-Cisneros, A.A. Sadun. Neuro-Ophthalmology, USC/Doheny Eye Institute, Los Angeles, CA. Purpose: The incidence, funduscopic findings, electroretinographic (ERG), flash visual evoked potential (VEP), and histopathologic findings of bilateral optic atrophy found in cynomolgus macaques used in regulatory toxicologic research are described. Methods: Cynomologus macaques randomly chosen as a test system for regulatory toxicologic studies had backgound lesions typical of bilateral optic atrophy, a condition previously described only in Rhesus macaques. Fundus photography, ERG, and Flash VEP were performed using standard techniques in some of the animals and histopathology was performed in all animals. Results: All of the affected animals were 2 to 3 years old and the large majority were of Vietnamese origin. In various studies between 0% and 24% of animals were affected. In one study with 14 affected animals, the histomorphological appearance exhibited a range of severity as follows: severe (6), moderate (3), slight (3) and minimal (2). 4 of the 6 with severe disease and 1 of the 3 with slight disease had optic nerve atrophy recorded on the screening fundus photography; all other animals were considered within the limits of normal variation. Affected animals were not detected by standard ERG or Flash VEP in this study. The morphologic changes consist of a decrease in ganglion cells in the macula and a decrease in axons in the temporal nerve fiber layer and the temporal optic nerve. The condition was always unrelated to the administration of test compounds. No affected animals had any detectable behavioral abnormalities. Conclusions: Bilateral optic atrophy has been reported in Rhesus macaques originating from China. We report the occurrence of the a similar syndrome in cynomolgus macaques of Vietnamese origin. Given the cynomolgus macque is commonly used in ophthalmic drug safety studies, it is important to characterize the nature of the finding. While the abnormality was not detected by ERG or flash VEP, the majority of markedly affected eyes could be identified by fundus evaluation. CR: R.R. Dubielzig, None; R. Leedle, Covance Laboratories Inc N, E; T.M. Nork, None; J.A. VerHoeve, None; B.J. Christian, Covance Laboratories Inc N, E. Support: None Purpose: Several studies have suggested that the receptor for advanced glycation end products (RAGE) are up-regulated in the microvasculature of Alzheimer’s disease (AD) to actively mediate the transport of β-amyloid across the blood-brain barrier into the brain from the systemic circulation. Once bound, the interaction of β-amyloid and RAGE could lead to a chronic inflammatory state amplified and perpetuated by the RAGE axis. The goal of this study is to determine whether there is any increase in the expression of RAGE in the microvasculature of the Alzheimer’s optic nerves. Methods: We looked at 10 retrobulbar optic nerves (1-3 mm from the globe) from donors previously diagnosed with AD. These were compared to 5 age-matched control optic nerves from individuals with no AD. All tissues were formalin-fixed and embedded in paraffin. Tissue sections were cut at 5 µm and immunostained with antibodies directed against human RAGE and endothelia (CD-31) both individually (immunoperoxidase) and for colocalization of these antigens (immunofluorescence) within optic nerve microvasculature. Tissue sections were observed on a standard bright field (immunoperoxidase) and confocal (immunofluorescence) microscope . The intensity and localization of immunolabeling for RAGE was qualitatively graded on a scale from 0 to 3. Grade 0 was defined as no staining, Grade 1 as mild staining, Grade 2 as moderate staining, and Grade 3 as strong staining. Results: Immunoreactivity for RAGE and endothelia were well defined. The immnolabelling for RAGE appeared “punctate” and the label for endothelia (CD-31) outlined their course within optic nerve connective tissue and fiber bundle parenchyma. In AD optic nerves, there was moderate to strong staining (Grade 2 and 3) for RAGE within the microvasculature, frequently outlining the blood vessels. In contrast, the staining for RAGE was largely minimal (Grade 1-2) in the microvasculature of control nerves. RAGE appeared to increase with age in both groups. Conclusions: Our observations suggest that AD is associated with an increase in RAGE within the microvasculature of the optic nerve. RAGE is a multi-ligand receptor that can bind to β-amyloid and other pro-inflammatory ligands. We postulate that the increase in RAGE within the microvasculature of AD optic nerve may contribute to the pathogenetic processes of optic neuropathy observed in a subpopulation of these patients. CR: M.Y. Wang, None; F.N. Ross-Cisneros, None; A.A. Sadun, None. Support: Oakley Alzheimer’s Research Foundation, Research to Prevent Blindness and NIH Grant EY03040 5346 - A297 An Immunohistochemical (IHC) Examination of Role of N-Methyl D- Aspartate (NMDA) Receptor as a Mediator of Damage in Optic Nerves of Patients with Chronic HIV Infection 5347 - A298 Follow-Up of Pattern-Reversal Visually Evoked Potential in Non-Affected Carriers From an Extensive Brazilian Leber Hereditary Optic Neuropathy (LHON) Pedigree M. Singh1, A. Shariati1, F.N. Ross-Cisneros1, W.R. Freeman2, A.A. Sadun1. 1NeuroOphthalmology, USC/Doheny Eye Institute, Los Angeles, CA; 2Ophthalmology, University of California San Diego, La Jolla, CA. P.Y. Sacai1, A. Berezovsky1, J.M. Pereira1, S.E.S. Watanabe1, L.D. Alves1, N.N. Cavascan1, R. Belfort, Jr.1, V. Carelli2, A.A. Sadun 3, S.R. Salomao1. 1Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil; 2Neurological Sciences, University of Bologna, Bologna, Italy; 3Doheny Eye Institute, University of Southern California, CA. Purpose: To determine if activation of NMDA receptors plays a role in the damage of optic nerves of the patients chronically infected with HIV. Methods: 28 retro bulbar optic nerves were collected at autopsy from 14 patients previously established to have chronic HIV infection. Six age matched control retro bulbar optic nerves were also collected. The nerves were immersion-fixed in 10% formalin. 3mm cross-sections of the nerves were embedded into paraffin and then cut on a microtome at 4microns. A two step indirect IHC staining method was employed using an HRP-conjugated secondary antibody reacting with a DAB substrate-chromogen system. The Primary antibody directed against human NMDA was diluted to 1:20. The slides were analyzed using a Zeiss Axioskop light microscope. The optic nerve’s IHC staining was graded on a scale from 0 to 4. 0 staining appeared to have none, or very trace evidence of DAB+ staining within the optic nerve tissue and the surrounding dura. A 4 appeared to have specific , heavy staining throughout the optic nerve. Results: We examined 38 nerves from 14 HIV patients. 4 of the 28 patients had a Grade 4 positive staining. Positive staining of NMDA was found in the neural tissue of HIV nerves as well as the control nerves, but the density of the staining was found to be more in the HIV nerves than in the negative control nerves. The density of NMDA receptors as evidenced by staining shows a continuum from being more dense to a decreasing density as the apoptotic process continues and neural tissue drop out occurs. These nerves ultimately show degeneration. Conclusions: The optic nerves of HIV positive patients have an up regulation of NMDA receptors which leads to excitotoxic injury to these nerves leading to cell loss and degeneration. This study shows the evidence of optic nerve damage in HIV positive patients as a result of NMDA receptor activation by the viral proteins. CR: M. Singh, None; A. Shariati, None; F.N. Ross-Cisneros, None; W.R. Freeman, None; A.A. Sadun, None. Support: Research to Prevent Blindness, and NIH Grants EY03040 Purpose: LHON is a maternally inherited disease associated with mitochondrial DNA point mutations and characterized by profound bilateral loss of central vision. Subclinical visual abnormalities have been reported in psychophysical and clinical assessment in asymptomatic of non-affected LHON carriers. The purpose of this longitudinal study was to investigate possible subclinical abnormalities by pattern-reversal visual evoked potential (PRVEP) in non-affected carriers from an extensive Brazilian 11778 LHON pedigree. Methods: Transient PRVEP (reversal rate = 1.9Hz; checkerboard stimuli 15’ and 60’; 100% contrast) was recorded from each eye in 15 non-affected carriers, aging from 19-57 years (mean= 38.7±12.3 yrs; median= 38.9; 10 females) in three visits (2002, 2006 and 2008). All participants had best corrected visual acuity of 20/20. In the first visit, an additional control group of 26 healthy subjects aging from 20-60 years (mean= 36.8±10.6 yrs; median= 35.7; 14 females) was tested. Latency (ms) of N75, P100 and N135 peaks and N75-P100 amplitude (µV) were determined for both stimuli size. Temporal dispersion of the response was calculated by the difference in latency between N135 and N75. Mann-Whitney test was used for comparison between carriers and controls. Kruskal-Wallis one-way analysis of variance was used to compare the three visits follow-up measurements. Results: In the first visit, statistically prolonged latencies were found in carriers when compared to controls with stimulus size 15’ (P=0.030) for P100 and N135 (P<0.001) and with stimulus size 60’ for N135 (P=0.004). Widened response was found in carriers when compared to controls with 15’and 60’stimuli size (P=0.013 and P=0.017, respectively). No differences were found for N75-P100 amplitudes between carriers and controls for both stimulus sizes. Intra-subject analysis for P100 latency and temporal dispersion was comparable in the three visits. Conclusions: Subclinical PRVEP abnormalities characterized by consistently prolonged latencies were found in asymptomatic non-affected carriers from this large 11778 LHON pedigree. Prolonged P100 latencies and larger temporal dispersion remain as persistant evidence of subclinical changes. CR: P.Y. Sacai, None; A. Berezovsky, None; J.M. Pereira, None; S.E.S. Watanabe, None; L.D. Alves, None; N.N. Cavascan, None; R. Belfort, Jr., None; V. Carelli, None; A.A. Sadun, None; S.R. Salomao, None. Support: International Foundation for Optic Nerve Disease (IFOND) Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 5344-5347 Thursday, May 7, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 5344 - 5356 / A295 - A307 517. Optic Neuropathy I Organizing Section: EY 5348 - A299 The Pattern of Abnormal Multifocal Visual Evoked Potential Latencies Involves Ceocentral and Arcuate Nerve Fiber Regions in Patients With Recovered Optic Neuritis E. Rosenblat1,2, F. Levin1, J.G. Odel1, D.C. Hood 3. 1Department of Ophthalmology, College of Physicians and Surgeons, New York, NY; 2Albert Einstein College of Medicine, Bronx, NY; 3Departments of Psychology and Ophthalmology, Columbia University, New York, NY. Purpose: To compare the pattern of visual field loss obtained with static automated perimetry (SAP) to the pattern of increased latency of the multifocal visual evoked potential (mfVEP) in patients with recovered optic neuritis (ON). Methods: 20 eyes of 20 patients with ON, ranging in age from 25 to 54, who underwent both mfVEP and 24-2 SAP testing within a 2 month period, were identified retrospectively. Patients with an attack within 6 months of testing were excluded. All patients had a visual acuity of 20/25 or better. Pattern reversal mfVEPs were recorded in response to a 44° diameter, 60 sector dartboard pattern (VERIS, EDI) using a montage of 4 electrodes as previously described.[1] The latency of the responses for each sector was calculated with a computer algorithm and compared to control values.[2] The locations of abnormal (p<5%) mfVEP latencies were displayed on monocular and intraocular probability plots [2], which were combined to show all abnormal points. The number of abnormal points was tabulated at each location. The number of abnormal (p<5%) points at each location was likewise tabulated for the total deviation SAP plot. Results: There were a significantly higher percentage of abnormal points on the mfVEP latency plots than on the SAP visual fields. 48.0% of the sectors of the mfVEP had abnormally long latencies, while 20.1% of the visual field locations on SAP were abnormal. Further, only 25.0% of the patients had abnormal mean deviations on SAP, while 95% of patients had significant mean mfVEP delays.[3] The most common locations of increased latency in the mfVEP were in the cecocentral and inferior arcuate regions. For the SAP fields, there were an insufficient number of abnormal points to confidently determine a pattern. Conclusion: The pattern of field locations with abnormally prolonged mfVEP latencies involved the cecocentral and arcuate nerve fiber bundle regions. These abnormalities were more severe than those seen on the SAP visual fields [4] and approximated both the pattern recently reported for the acute stage of optic neuritis on SAP visual fields [5] and the classic pattern of cecocentral involvement found at the tangent screen.[6] 1. Hood, Zhang, et al. IOVS, 2000; 2. Hood, Ohri, et al. Doc Ophthal,2004; 3. Hood, Chen, et al. TAOS, 2006; 4. Hood, Odel, Zhang IOVS, 2000; 5. Nevalainen, Krapp, et al. Graefes, 2008; 6. Chamlin Arch Ophthal, 1953. CR: E. Rosenblat, None; F. Levin, None; J.G. Odel, None; D.C. Hood, None. Support: NIH Grant EY02115 5349 - A300 Spike Gene Mediates Viral-Induced Experimental Optic Neuritis K.S. Shindler1, M. Dutt1, J. Das Sarma2. 1Ophthalmology, Univ Pennsylvania Scheie Eye Institute, Philadelphia, PA; 2IISER-Kolkata, Kolkata, India. Purpose: Infection of mice with neurovirulent strains of mouse hepatitis virus (MHV) is used as a model for virus-induced demyelination that mimics many pathologic features of multiple sclerosis. A significant incidence of optic neuritis occurs in mice infected with a demyelinating strain of MHV (MHV-A59), but not with the nondemyelinating strain, MHV-2. Mechanisms underlying this differential induction of optic neuritis are not known. We examined the potential role of spike, a glycoprotein involved in virus-host attachment, in mediating induction of optic neuritis. Methods: Four week-old C57Bl/6 mice were inoculated intracranially with 50% LD50 dose of RSA59 strain (20,000 PFUs) or RSMHV2 (100 PFUs). RSA59 and RSMHV2 strains of MHV are isogenic (background is from demyelinating strain MHV-A59) except for the spike gene. Mice were sacrificed 5 and 30 days post-innoculation. 5 micron longitudinal sections of isolated optic nerves were assessed by H & E and immunohistochemistry for inflammatory cell markers. Axonal integrity was assessed by silver staining. Results: RSA59 induced optic neuritis, characterized by inflammatory cell infiltration of optic nerves, by day 5 post-innoculation, with significant loss of myelin and axonal damage detected at day 30, similar to effects of the parent virus MHV-A59 seen in prior studies. RSMHV2, however, induced little or no optic nerve inflammation with preserved myelin and retinal ganglion cell axons. Conclusions: Results demonstrate that a neurovirulent spike gene is required for MHV strains to induce optic neuritis, as the spike gene from the non-demyelinating MHV2 strain rendered MHV-A59 incapable of inducing optic nerve inflammation, demyelination and axonal damage. The spike protein is a potential target for disrupting virus-host attachment that may have a role in treating optic neuritis and multiple sclerosis. CR: K.S. Shindler, None; M. Dutt, None; J. Das Sarma, None. Support: NIH grant EY015098, a Career Development Award from RPB, and the F. M. Kirby Foundation to KSS; FG1431-A-1 and RG3774A2-1 from the NMSS, and M.E.Groff Surg. Med. Res. and Ed. Charitable Trust to JDS 5350 - A301 Optic Nerve Size May Reflect Pattern of Axonal Degeneration in Leber’s Hereditary Optic Neuropathy 5351 - A302 Immunohistochemical Study of High Mobility Group Box 1 in Alzheimer’s Disease Optic Nerves K.R. Tozer1, C.D. Robinson1, D. Aggarwal1, F.N. Ross-Cisneros1, M.N. Moraes-Filho2, A. Berezosky3, S.R. Salomao3, V. Carelli4, A.A. Sadun1. 1Neuro-Ophthalmology, Doheny Eye Institute and Keck School of Medicine, University of Southern California, Los Angeles, CA; 2Instituto de Olhos de Colatina, Colatina, Brazil; 3Ophthalmology, Federal University of Sau Paulo, Sau Paulo, Brazil; 4Dipartimento di Scienze Neurologiche, Universitá di Bologna, Bologna, Italy. A.B. Savoia, D. Aggarwal, F.N. Ross-Cisneros, A.A. Sadun. Neuro-Ophthalmology, USC/Doheny Eye Institute, Los Angeles, CA. Purpose: To perform a morphometric analysis of four optic nerves from two related Leber’s Hereditary Optic Neuropathy (LHON) patients and study the pattern of degeneration in relationship to different states of disease progression. Methods: Optic nerves from two LHON (11778/ND4 mtDNA mutation) affected brothers with moderate and severe optic atrophy respectively were studied and compared. Both patients had been followed as part of a large systematic prospective ophthalmological investigation of LHON. The optic nerves were fixed, plastic embedded, and stained with p-phenylenediamine to allow for axon counting. For total axon counts, a nerve cross section was partitioned into five different regions. Photos were taken at 1000X magnification and axons were counted by hand. Total counts and axon densities were calculated. Total cross sectional areas were also calculated for the optic nerves using the “Spot II Advanced” software package. Results: Two different degeneration patterns were observed. One brother (patient 1) had a focal area of degeneration in the temporal zone of both eyes with sparing of the periphery, while the other brother (patient 2) had a diffuse pattern of degeneration. Total axon counts per optic nerve for patient 1 were 333,192 (OD) and 269,319 (OS) while patient 2 had counts of 22,889 (OD) and 22,376 (OS). The cross sectional area of the optic nerves were 5.79(OD) and 7.97 (OS) mm 2 for patient 1, and 3.29(OD) and 3.35(OS) mm 2 for patient 2. Conclusions: This study provides morphometric evidence of the relationship between different stages of LHON and optic nerve size. Since both patients showed extensive levels of degeneration well below the approximately 1.0 million axon per optic nerve average for this age group (Johnson, et. al; Age 1987), it is not likely that the entire difference in nerve size can be attributed to the level of degeneration. Hence, even taking into account that increased degeneration leads to more atrophic shrinkage of the optic nerve, a smaller, and thus more crowded, optic nerve may be associated with more severe and diffuse patterns of degeneration. CR: K.R. Tozer, None; C.D. Robinson, None; D. Aggarwal, None; F.N. Ross-Cisneros, None; M.N. Moraes-Filho, None; A. Berezosky, None; S.R. Salomao, None; V. Carelli, None; A.A. Sadun, None. Support: None Purpose: To investigate the presence of High Mobility Group Box 1 (HMGB1) in Alzheimer’s disease (AD) optic nerves. HMGB1 is a non-histone DNA binding protein which can translocate from the nucleus to the cytoplasm during states of cellular stress or damage. It can then act as both a cytokine and ligand stimulating the receptor for advanced glycation end products (RAGE) when released extracellularly resulting in inflammation and tissue damage. Methods: Optic nerve specimens were obtained at autopsy from twelve patients with AD and compared to six normal age-matched control tissues. AD tissues were supplied by our Alzheimer’s Disease Research Center (ADRC) and controls were purchased through local eye banks. Tissues were immersion fixed in neutral buffered formalin, dissected into cross-sectional profiles just proximal to the globe, then processed and embedded into paraffin blocks. Sections were cut at 5 µm and immunostained, using an indirect method with horseradish peroxidase and diaminobenzidine as the substratechromogen, with a rabbit anti-human HMGB1 polyclonal antibody at a dilution of 1:1,000. Light microscopic images were viewed on a Zeiss Axioskop microscope and captured by a digital camera and saved to a computer. Results: Control optic nerves immunostained for HMGB1 demonstrated very specific nuclear but not cytoplasmic staining in most cells. AD tissues revealed both nuclear and cytoplasmic localization of the chromogen. The cytoplasmic staining was usually intense and highlighted this region’s entire area. It was also observed that the cell cytoplasm appeared vacuolated with an empty space often circumscribing the entire, though intact, nucleus. Glial cells appeared to be the primary target of the immunostaining with astrocytes being the most common glial cell labeled. Conclusions: HMGB1 is a non-histone DNA binding protein that can act as a ligand to RAGE which can initiate pro-inflammatory pathways. Increased presence of HMGB1 in cytoplasm of glial cells in AD optic nerves may indicate that HMGB1, when released extracellularly, may bind to RAGE thus mediating inflammatory pathways. Hence, HMGB1 may play a role in the pathogenesis of optic neuropathy as observed in a subpopulation of Alzheimer’s disease patients. CR: A.B. Savoia, None; D. Aggarwal, None; F.N. Ross-Cisneros, None; A.A. Sadun, None. Support: Research to Prevent Blindness, Oakley Alzheimer’s Research Foundation, NIH Grant EY03040 Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 5348-5351 Thursday, May 7, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 5344 - 5356 / A295 - A307 517. Optic Neuropathy I Organizing Section: EY 5352 - A303 Comparison of Humphrey Matrix Frequency Doubling Technology in the Assessment of Pre-Chiasmal and Post-Chiasmal Disease 5353 - A304 Novel Applications of Rarebit Perimetry M.K. Yoon, C. Kum, S. Day, T.J. McCulley. Ophthalmology, University of California San Francisco, San Francisco, CA. S.K. Houston, III1A, E.D. Weber1B,2, S.A. Newman1B, S.F. Koga1C. ASchool of Medicine, B Ophthalmology, CNeurosurgery, 1University of Virginia, Charlottesville, VA; 2 Ophthalmology, Walter Reed Army Medical Center, Washington, DC. Purpose: Frequency doubling technology perimetry (FDT) has been used to assess visual function in patients with neuro-ophthalmic abnormalities of the anterior and posterior visual pathways. Initial reports suggested that FDT is less accurate assessing defects of the posterior visual pathway. In this study, we compared Humphrey Matrix FDT to standard automated perimetry (SAP) in the assessment of pre- and postchiasmal disease. Methods: The charts of all patients with neuro-ophthalmic disease, involving the anterior (n=27) and posterior (n=9) visual pathways, tested with both Humphrey Matrix FDT (30-2) and Humphrey Visual Field Analyzer (30-2 SITA standard) from July 2006 to November 2008, were retrospectively reviewed. Involved eyes of unilateral disorders were included; the better and worse eyes were alternated in bilateral disease. Similarity between the tests were numerically graded 1 (poor), 2 (fair), and 3 (good) for total (TD) and pattern deviation (PD) plots. Additionally, the extent of defects were compared, with more extensive field loss defined as 5 or more abnormal test locations at P < 0.5%. Spearman coefficient was calculated for both mean deviation (MD) and pattern standard deviation (PSD). Results: Etiologies included compressive lesions (n= 11), NAION (n= 5), stroke (n= 4), IIH (n=3), optic nerve drusen (2), and other (n= 11). The average similarities between the FDT and SAP for PD in anterior and posterior disease were 2.31 and 2.44 (p = 0.44, paired T-test); and for TD were 2.46 and 2.5, respectively (p = 0.29). The extent of defect was same in 55% on PD and 66% on TD. Spearman coefficient for anterior and posterior disease for MD was 0.86 and 0.93, and for PSD was 0.78 and 0.63, respectively. Conclusions: Although originally developed for glaucomatous field defects, the Humphrey Matrix perimeter has reasonable correlation to SAP in anterior and posterior pathway disease. Our series, which uses 30-2 field analysis, demonstrates fair to good correlation between SAP and FDT in both anterior and posterior neuroophthalmic disease. This suggests that the poor correlation with earlier versions of FDT was due to technical aspects of the perimeter, and not due to differing aspects of visual function being tested by FDT and HVF. CR: M.K. Yoon, None; C. Kum, None; S. Day, None; T.J. McCulley, None. Support: That Man May See Purpose: Rarebit perimetry (RBP) was developed for the detection of early damage to the afferent visual system. Testing is performed on a standard personal computer with a 15” LCD screen and utilizes suprathreshold stimuli that probe for the completeness of the neuroretinal architecture. Previous studies have shown that RBP is able to detect visual field defects in glaucoma and neuro-ophthalmologic disorders. Rarebit perimetry has also been shown to be more sensitive to early and subtle damage to the afferent system compared to standard automated perimetry (SAP). The purpose of the study was to determine the feasibility of bedside testing with rarebit perimetry and compare results with standard automated perimetry. Methods: 29 eyes of 15 patients admitted with neurologic or neurosurgical disease affecting the afferent visual system were tested. Visual fields using RBP were tested on a laptop computer at the bedside, while visual fields tested using SAP (Humphrey field analyzer) were performed in the clinic. Results of the two tests were compared by a neuro-ophthalmologist blinded to the diagnosis. Results: 21 of 29 (72%) visual fields corresponded between RBP and SAP. Additionally, RBP detected 5 defects (17%) in patients who had normal results on SAP. Finally, 15 of 15 patients preferred RBP for ease of testing and convenience. Conclusions: Rarebit perimetry is an easy, convenient, and reliable way to test the afferent visual pathways at the bedside. CR: S.K. Houston, III, None; E.D. Weber, None; S.A. Newman, None; S.F. Koga, None. Support: None 5354 - A305 Age-Corrected Normative Data for the Entire (80 Degree) Visual Field, Assessed With a New Fast Thresholding Estimation (GATE) 5355 - A306 Comparison Between Age-Corrected Normative Threshold Values for the Static Stimulus Sizes Goldmann III and V, Assessed With a New Fast Thresholding Estimation (GATE) U. Schiefer1, S. Frick1, J. Nevalainen2, J. Grobbel1, E. Krapp1, B. Selig1, R. Vonthein 3, R.G. Weleber4, J. Paetzold1. 1Institute for Ophthalmic Research, Centre for Ophthalmology, Tuebingen, Germany; 2University Eye Hospital Oulu, Oulu, Finland; 3Institute of Medical Biometry and Statistics, University of Luebeck, Luebeck, Germany; 4Casey Eye Institute, Oregon Health & Science University, Portland, OR. Purpose: To assess age-corrected normative differential luminance sensitivity (DLS) values for automated static perimetry with a new, fast strategy (GATE = German Adaptive Threshold Estimation) for the entire (80 degree) visual field. Methods: Eighty-one normal subjects, aged from 10 to 79 years were enrolled in this study, which was performed on the new Octopus 900 perimeter (HAAG-STREIT Inc., Koeniz, Switzerland). Eighty-six static stimuli (Goldmann size III = 26´) up to a maximal eccentricity of 80 degrees, with a condensation towards the visual field centre, were presented on a homogeneous background under photopic conditions (luminance level 10 cd/m²). A fast thresholding 4-2 dB algorithm with at least one reversal was used. Local DLS values were estimated by applying the maximum likelihood (ML) procedure. A smooth mathematical model was fitted to the data set, allowing to predict the local DLS values for any location of the entire visual field. Results: Model fit was satisfactory (R² = 0.72). The residual standard deviation over the entire 80 degree visual field amounted to 2.52 dB. The number of questions asked (mean) was 338 for the GATE strategy (compared to 410 for the conventional 4-2 dB bracketing algorithm) in this cohort of normal subjects. Examination duration (median, without breaks) was 13.5 min. (95% RI 10.7 - 20.4 min). Conclusions: A smooth mathematical model allows for the prediction of local differential luminance thresholds of normal subjects for any location within the entire 80 degree visual field, obtained with the new Octopus 900 perimeter. In normal subjects, the new, fast GATE strategy reduces the number of questions asked by approximately 18%, compared to a full threshold bracketing algorithm. Subsequent examinations with GATE are related to previous exams and therefore further reduce the examination duration. CR: U. Schiefer, Haag-Streit, Koeniz, Switzerland, C; S. Frick, None; J. Nevalainen, None; J. Grobbel, None; E. Krapp, Haag-Streit, Koeniz, Switzerland, F; B. Selig, None; R. Vonthein, None; R.G. Weleber, None; J. Paetzold, Haag-Streit, Koeniz, Switzerland, F. Support: Haag-Streit CT: If Other, enter the registry site and corresponding number J. Dietzsch1, J. Grobbel1, J. Nevalainen2, S. Frick1, E. Krapp1, B. Selig1, R. Vonthein 3, R.G. Weleber4, J. Paetzold1, U. Schiefer1. 1Centre for Ophthalmology, Institute of Ophthalmic Research, University of Tuebingen, Tuebingen, Germany; 2University Eye Hospital Oulu, Oulu, Finland; 3Institute of Medical Biometry and Statistics, University of Luebeck, Luebeck, Germany; 4Casey Eye Institute, Oregon Health & Science University, Portland, OR. Purpose: To assess the differences of the age-corrected normative differential luminance sensitivity (DLS) values for automated static perimetry with Goldmann stimulus size III and V using GATE (German Adaptive Threshold Estimation). Methods: Sixty-six normal subjects (10 to 79 years) were examined with the Octopus 900 perimeter. The grid of 86 test locations up to 80 degrees was condensed towards the center of the visual field. Static stimuli of Goldmann size III and size V were presented during two sessions on a photopic background (10 cd/m²). The fast thresholding algorithm GATE was used with an initial step size of 4 dB and at least one reversal. DLS values were estimated by applying the maximum likelihood (ML) procedure. Two smooth mathematical models were fitted separately to the two data sets, in order to predict the local DLS values for any location of the entire visual field. Results: The difference between the predicted DLS values (V-III) was calculated to assess the differential shape of the fitted models. This difference varied depending on the age from +3 dB to +5 dB in the center, showed an interaction between age and eccentricity outside the center, and in the periphery ranged from +8 dB to +11 dB. Conclusions: A smooth mathematical model allows the estimation of the differences in measuring the normative local DLS thresholds. For normal subjects a DLS difference (V-III) of approximately +3 dB to +5 dB can be observed in the centre of the visual field. The DLS difference was greatest in the periphery, decreases with the age for low eccentricity values, and increases with age for high eccentricity values. CR: J. Dietzsch, Heidelberg Engineering, F; J. Grobbel, None; J. Nevalainen, None; S. Frick, None; E. Krapp, None; B. Selig, None; R. Vonthein, None; R.G. Weleber, None; J. Paetzold, Haag-Streit, F; U. Schiefer, Haag-Streit, C. Support: Heidelberg Engineering, Haag-Streit CT: If Other, enter the registry site and corresponding number Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 5352-5355 Thursday, May 7, 8:30 AM - 10:15 AM Hall B/C Poster Session Program Number/Board # Range: 5344 - 5356 / A295 - A307 517. Optic Neuropathy I Organizing Section: EY 5356 - A307 Three-Dimensional Optic Nerve Learning Module for Physicians in Training A.S. Khouri1, R.D. Fechtner1, J.M. Liebmann2. 1Ophthalmology, UMD New Jersey Medical School, Newark, NJ; 2Ophthalmology, New York Eye and Ear Infirmary, New York, NY. Purpose: The aim of this study was to assess the educational impact of a novel 3-dimensional ON learning module for physicians in training. Methods: Current medical school curricula rely on text book images of the optic nerve (ON) for learning. The ON is a 3-dimensional structure that is best studied through stereoscopic images. Medical students and non-ophthalmology residents participated in the evaluation of a 3-dimensional ON learning module. The learning module consisted of normal and glaucoma images included during a short course presentation. All images were high resolution and obtained by simultaneous stereoscopic imaging (Nidek 3-Dx camera, Gamagori, Japan, Nikon D1x 6.1 megapixel, Tokyo, Japan). Images were mounted on View-Master (Fisher Price Inc. NY, USA) reels for stereoscopic viewing by participants. To assess the educational value of the module, each participant was asked to classify 25 ON images as normal or glaucoma before and again after the course presentation. Correct classification scores, sensitivity and specificity were calculated before and after the presentation. Results: 15 physicians in training participated in the learning module. A total of 750 ON images were classified. The mean time for a training session was 14 minutes. Correct classification improved in all participants (Mean 21%, SD 13%). Compared to baseline sensitivity and specificity of correct classification significantly improved after training. The results are summarized in the table. Conclusions: In this pilot study the recognition of normal and glaucoma ON was significantly improved after a single training with the 3-dimensional learning module. This learning tool is practical and effective and may be incorporated into academic curricula. CR: A.S. Khouri, None; R.D. Fechtner, None; J.M. Liebmann, None. Support: Research to Prevent Blindness, NY, NY Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 5356 Thursday, May 7, 11:15 AM - 1:00 PM Room 114 Paper Session Program Number Range: 5662 - 5668 529. Optic Neuropathy II Organizing Section: EY 5662 - 11:15AM Identification and Characterization of a Novel 102 AA-Duplication in the GTPase Domain of Opa1 5663 - 11:30AM Light-Induced Melatonin Suppression in Mitochondrial Optic Neuropathies N. Fuhrmann1, Y. Kamenisch2, B. Leo-Kottler3, B. Wissinger1, M.V. Alavi1. 1Centre of Ophthalmology, Molecular Genetics Laboratory, Tuebingen, Germany; 2 Department of Dermatology, University Clinics Tuebingen, Tuebingen, Germany; 3 Department of Pathophysiology of Vision and Neuro-ophthalmology, University Eye Hospital Tuebingen, Tuebingen, Germany. C. La Morgia1, E. Sancisi1, A. Munarini2, V. Mantovani2, P. Barboni 3, R. Liguori1, P. Montagna1, A.A. Sadun4, V. Carelli1. 1Department of Neurological Sciences, University of Bologna, Bologna, Italy; 2Biomedical Centre Applied Research CRBA, S.Orsola-Malpighi University Hospital, Bologna, Italy; 3D’Azeglio Ophtalmologic Centre, Bologna, Italy; 4Doheny Eye Institute, University of Southern California, Keck School of Medicine, Los Angeles, CA. Purpose: Nowadays it is quite kerfuffle-free to differentiate autosomal dominant optic atrophy (ADOA) from Leber’s hereditary optic neuropathy (LHON) due to the different mode of inheritance and thanks to molecular genetic diagnostics. The Nosology of these two hereditary optic neuropathies goes back as far as the 1950ies when W. Jaeger put his hypothesis on the basis of the examination of a large German family. Strikingly, no mutation has been identified in this family to date. Methods: We used Multiplex Ligation Probe Amplification (MLPA), long distance PCR and cDNA analyses to assess copy number variations in the Opa1 gene in this family. Two patients underwent full ophthalmologic examinations and agreed to skin biopsies. Therewith we investigated the consequences of this mutation on transcript and protein level, assessed mitochondrial network organization and mtDNA integrity. Results: Patients presented with a classical ADOA. MLPA analysis revealed a duplication of the exons 7-9 which was confirmed by long distance PCR and cDNA analysis. Segregation was verified in 53 available members of the updated pedigree and we calculate a penetrance of 88%. The mutation results in an inframe duplication of 102 AA within the GTPase domain (p.L227_K328dup102). Qualitative and quantitative Western blot analysis showed a reduction of all OPA1 isoforms when compaired to actin. In regards to other mitochondrial proteins we see an increase of Opa1 to 200%. In line we find an accumulation of the OPA1 precursor protein, but no additional bands representing protein from the mutated allele. Quantitative cDNA analysis revealed a reduction of the mutated allele whereas the overall OPA1 expression was elevated more than 2 times. Fibroblasts present with significantly fragmented mitochondrial network even when cultured under basal conditions. Conclusions: More than 50 years past its first description we identified the disease causing mutation in the family that initially laid the bases for the nosology of inherited optic neuropathies. With the clinical, genetic and cell biological characterisation of this family we span nearly one century of research in optic neuropathies giving new insights into the disease mechanism of ADOA. CR: N. Fuhrmann, None; Y. Kamenisch, None; B. Leo-Kottler, None; B. Wissinger, None; M.V. Alavi, None. Support: None Purpose: To test the integrity of the retino-hypothalamic tract (RHT), originating from the intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs), in mitochondrial optic neuropathies (ON), which selectively affect retinal ganglion cells (RGCs). The non-rod/cone photoreceptors ipRGCs convey the detection of light irradiance to the brain through the RHT, photoentraining circadian rhythms and contributing to the pupillary light reflex (PLR). Methods: Melatonin suppression test (MST) was performed in five Leber hereditary optic neuropathy (LHON) and four dominant optic atrophy (DOA) patients, and in nine gender and age-matched controls. A baseline and suppression night tests with monochromatic (470 nm) blue light between 1:30 to 3:30 am were performed. Melatonin was assayed by radioimmunoassay on plasma samples collected hourly from 12:30 pm to 3:30 am. The suppression score was calculated comparing the suppression night melatonin to the baseline night and statistics was run by One-way analysis of variance. Clinical ON severity was determined by retinal nerve fiber layer thickness (RNFL) as evaluated with Optical Coherence Tomography (OCT). All subjects completed self-administered questionnaires (Pittsburgh sleep quality index, Morningness and eveningness, Epworth Sleepiness Scale, Life quality index SF-36, Zung Anxiety and Depression Scale). Results: A significant suppression of melatonin plasma levels by light was observed both in control subjects (67% ± 17%) and patients (LHON 65% ± 25% ; DOA 53% ± 33%). The suppression score was not statistically different among groups. All patients had severe optic atrophy and normal PLR. OCT evaluation documented an average RNFL of 52 µm ± 9 in LHON and 59,3µm ±5,8 in DOA (controls 97,3µm±8,4). Self-administered questionnaires showed statistical differences between controls and ON patients only for SF-36 A and C items. Conclusions: We demonstrate in both LHON and DOA a substantial preservation of the circuit sustaining the photic input to the circadian system (RHT), as documented by suppression of melatonin secretion by light and PLR preservation in these blind patients. CR: C. La Morgia, None; E. Sancisi, None; A. Munarini, None; V. Mantovani, None; P. Barboni, None; R. Liguori, None; P. Montagna, None; A.A. Sadun, None; V. Carelli, None. Support: Telethon Grant GGP06233 to VC 5664 - 11:45AM Retinal Nerve Fiber Layer Birefringence: Acute Reduction and Recovery in Optic Neuritis 5665 - 12:00PM Demonstration of Trans-Synaptic Retrograde Loss of Retinal Ganglion Cell Loss Following Retrogeniculate Lesions in Humans Using Optical Coherence Tomography(OCT) M.J. Kupersmith1, Q. Zhou2, G. Mandel3, V. Atkinson4, S. Anderson 5, R. Kardon6. 1 Roosevelt Hospital and NYEE, New York, NY; 2Zeiss-Meditec, Inc, Sand Diego, CA; 3Roosevelt Hospital, New York, NY; 4Zeiss Meditec, San Diego, CA; 5 Ophthalmology, Iowa University, Iowa City, IA; 6Ophthalmology, University of Iowa and Veterans Hosptial, Iowa City, IA. P. Jindahra1, A. Petrie2, G.T. Plant1. 1Neuro-Ophthalmology, The National Hospital for Neurology and Neurosurgery, Queen square, London, United Kingdom; 2 Biostatistics Unit, Eastman Dental Institute, University College London, United Kingdom. Purpose: To determine if retinal nerve fiber layer (RNFL) birefringence, thought to be mostly associated with axonal microtubule density, is affected at the onset of optic neuritis and if it changes over 6 months. Methods: 10 subjects had prospective good quality imaging of both eyes with OCT (Stratus) for RNFL thickness and GDx (in ECC mode) for RNFL phase retardation at a mean 6.6 days of vision loss and at 1, 3 & 6 months. We analyzed RNFL measurements divided into 12 clock hour sectors at all visits. For each sector, we calculated percentage change in RNFL thickness for OCT and in RNFL phase retardation for GDx compared to the corresponding sector of the fellow unaffected eye. For each visit, the percentage birefringence change was calculated as the percentage phase retardation change minus the percentage RNFL thickness change per eye per sector and then averaged over the subjects. We evaluated the trends of mean overall change (across sectors) based on RNFL thickness, retardation, and birefringence. Results: The RNFL thickness was about 25% higher and retardation was about 7% higher compared to the fellow eye at baseline. Compared to the OCT thickness, GDx retardation was more stable over 6 months, with approximately 9% cumulative retardation reduction. (Figure shows change for OCT and GDx over 6 months). The 6-month cumulative amount of reduction in retardation (2%) was similar to the 6-month OCT thickness loss (8.6%) when compared to the fellow eye. The RNFL birefringence was approximately -17.7% at onset and rebounded at 6 months. Conclusions: The acute calculated drop in birefringence may result from reduction in microtubule density due to intra-axonal swelling or microtubular alterations in response to injury or from extracellular edema. Some of this calculated reduction seems to be recoverable. Since OCT measures RNFL thickness and GDx measures RNFL retardation, combining the two may reveal information that distinguishes recoverable tissue swelling from permanent damage. CR: M.J. Kupersmith, Teva Pharmaceutical, C; Q. Zhou, Zeiss Meditec, Inc, E; G. Mandel, None; V. Atkinson, Zeiss Meditec, Inc, E; S. Anderson, None; R. Kardon, None. Support: Pearle Vision Foundation, Teva Pharmaceutical Purpose: Trans-synaptic retrograde loss of retinal ganglion cells in humans is well established with congenital lesions but controversial with acquired pathology. The aim of the study was to investigate whether thinning of the retinal nerve fibre layer (RNFL) can be detected in such cases using OCT. Methods:The thickness of the RNFL was measured in microns using Stratus OCT. There were three patient groups all with occipital damage: cases of acquired homonymous hemianopia (AHH; n=19); congenital homonymous hemianopia (CHH; n=7) and a mixed group of both congenital and acquired homonymous quadrantanopia (CAHQ). The results were compared with the right and the left eyes of 22 controls. A repeated measures analysis of variance was performed to compare the mean values in the different groups, separately for the eyes with temporal hemianopia (crossing fibre defect eyes, CFD) and for the eyes with nasal hemianopia (non-crossing fibre defect eyes, NonCFD). Results: The mean RNFL in the CFD eyes was 79.8μ (SD=35.1μ) in AHH, 72.7μ (33.2μ) in CHH, and 100.8μ (35.4μ) in the right eyes of the controls. The mean RNFL in nonCFD eyes was 83μ (29.5μ) in AHH, 73.4μ (26μ) in CHH, and 101.4μ (36.6μ) in the left eyes of the controls. In the CFD eyes, the mean RNFL was significantly greater in the control group than in either of the hemianopia groups (p<0.001). In the NonCFD eyes, there were significant differences between all three RNFL group means (p<0.001). For the CAHQ group the mean RNFL in the CFD eyes was 88.2μ (35.1μ) and in the NonCFD eyes was 89.2 μ (30.4μ). The mean RNFL was significantly greater in the controls than in the quadrantanopia group (p=0.003) in both eyes. The results were also analysed by dividing the peripapillary nerve fibre into 12 equal sectors around the circumference of the optic disc. These results demonstrated that the RNFL thinning corresponded to the known trajectories of the crossing and non-crossing fibres entering the optic disc and also to the retinal region of origin corresponding to the visual field loss. Conclusions: We have shown that trans-synaptic retrograde degeneration of retinal ganglion cells occurs in both congenital and acquired post-geniculate lesions in humans and that the magnitude of the loss is similar in both. CR: P. Jindahra, None; A. Petrie, None; G.T. Plant, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 5662-5665 Thursday, May 7, 11:15 AM - 1:00 PM Room 114 Paper Session Program Number Range: 5662 - 5668 529. Optic Neuropathy II Organizing Section: EY 5666 - 12:15PM Optic Nerve Compartment Syndrome. An Experimental Animal Model 5667 - 12:30PM Quantitative Assessment of the Extracellular Matrix in the Optic Nerve Head H.E. Killer1, M. Harlev2, U. Ziegler3, P. Groscurth 3, N.R. Miller4, P. Meyer5, S. Dotan6, G. Jaggi7. 1Ophthalmology, Kantonsspital Aarau / University of Basel, Aarau, Switzerland; 2Animal Research Center, Hadassah Hebrew-University Hospital, Jerusalem, Israel; 3Anatomy, Institute of anatomy, University of Zurich; Switzerland, Zürich, Switzerland; 4Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore USA, Baltimore, MD; 5Ophthalmology, University of Basel, Eye Institute, Basel, Switzerland; 6 Ophthalmology, Hadassah Hebrew-University Hospital., Jerusalem, Israel; 7 Ophthalmology, Kantonsspital Aarau, Aarau, Switzerland. D.J. Brown, A. Lay, L. Lam, S. Said, J. Jester, D.S. Minckler. The Gavin Herbert Eye Institute, University of California, Irvine, Orange, CA. Purpose: To report the results of experimental optic nerve compartmentation in sheep. This study was performed according to the ARVO guidelines for animal research and was approved by the local ethical committee Methods: 4 female Dorper sheep were selected. Age was between 1-1.5 years, weight between 30-35 kg. Orbitomy was performed under general anesthesia. The optic nerve on one side was gently ligated with a silicone sling near the optic canal and left in place in order to impair cerebrospinal fluid circulation. The optic nerves were removed after three weeks and were worked up for histology. Results: Light microscopy, transmission EM and scanning EM Light demonstrates loss of axons in the periphery of the nerve at the site of the ligature. Behind the globe, remote from the ligature, the axons loss is more pronounced, reaching in to the center of the cross section. Transmission electron microscopy shows destruction of myelin and axons while most of the cellular components of the optic nerve appear intact. Conclusions: Light microscopy, transmission EM and scanning EM demonstrate axon loss after experimental compartmenation of the optic nerve. The cross section most involved is located distal to the ligation behind the globe. This pattern of axon loss is unlikely to be caused by local trauma via the ligature. We suggest that statis of CSF with accumulation of biologically active substances, such as L-PGDS my harm the the unmyelinated axons and mitochondria in the bulbar region behind the globe, causing anteriograde axon degeneration. Further studies including CSF analysis are necessary to elucidate the pathophysiology of the axon loss pattern. Reference: Killer HE, Jaggi G, Flammer J, Miller NR, Mironov A. Cerebrospinal fluid dynamics between the intracranial -and the subarachnoid space of the optic nerve. Is it always bidirectional? Brain 2007 129(4):1027-1030; CR: H.E. Killer, None; M. Harlev, None; U. Ziegler, None; P. Groscurth, None; N.R. Miller, None; P. Meyer, None; S. Dotan, None; G. Jaggi, None. Support: Emilia Guggenheim-Schnurr-Stiftung Purpose: Our goal was to quantitatively assess the structural components of collagen and elastin in 3-dimensions across of the human optic nerve head (ONH). Methods: Five pairs of eyes ranging in age from 59-84 were fixed in 4% paraformaldehyde in PBS overnight at 4°C. The ONH was then removed, embedded in low melting point agarose and then serially sectioned at 250 um using a Vibratome. Sections were collected as a continuous series and nonlinear optical images of two photon excited fluorescence (TPEF, elastin) and second harmonic generated signals (SHG, collagen) were acquired using a Zeiss 510 Meta LSM and Chameleon femtosecond laser and a 10X 0.3 NA objective. For each section, a total of 24 overlapping multi-plane images (512 x 512 pixels, 1.8 um lateral resolution) arranged in a grid (6 X4) were collected. Images from each section were then concatenated into a single Z-stack mosaic of 3072x2048 pixels X 125 um, 8-bit multichannel image file. Mosaics were then processed using a median filter (2x2 pixel) to reduce noise and normalized to match gray levels. The Z-stacks were then demarcated into regions, a threshold established to exclude background pixels and the percent area of included pixels recorded for each channel using Metamorph software (Molecular Dynamics). Statistical analyses were performed using Prism 4.0 (Graphpad). Results: We demonstrate that, as expected, the SHG signal co localized with the pattern of immunofluorescence achieved with an anti-collagen antibody. The TPEF signal correlated well with the pattern of immunofluorescence achieved with an antielastin antibody. Using the SHG to indicate collagen and TPEF to indicate elastin, the volume occupied by these matrix components varied considerably with position in the ONH. Significantly, the proportion of elastin relative to collagen was markedly higher in the prelaminar canal immediately anterior to the collagen beams of the lamina. This enrichment in elastin content was also noted in the tissues immediately adjacent to the canal wall. Conclusions: The utilization of a multiphoton laser system allows one to obtain detailed views of the structural components of the ONH that is optically based and non-invasive. In addition, as the entire ONH can be assessed the data can be objectively and quantitatively analyzed to determine the microscopic density of collagen and elastin with the ONH. CR: D.J. Brown, None; A. Lay, None; L. Lam, None; S. Said, None; J. Jester, None; D.S. Minckler, None. Support: NIH Grant EY16663, NIH Grant EY017959, Research to Prevent Blindness, Discovery Fund for Eye Research 5668 - 12:45PM Investigation of Fibril Ultrastructure in Optic Nerve by X-Ray Scattering J.R. Lewis1, K.M. Meek 2, J.P.R.O. Orgel3. 1Ophthalmology, Biomed Engineering, The Ohio State University, Columbus, OH; 2Biophysics Group, Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom; 3CSRRI, Dept. BCPS; Dept. Biochemistry, Illinois Institute of Technology; Chicago Medical School, Chicago, IL. Purpose: Fibrillar species indicative of equatorially oriented collagen were identified by wide-angle X-Ray diffraction in porcine optic nerve dissections providing proofof-concept for X-Ray analysis of human optic nerve tissue in situ. Methods: Sections of porcine optic nerve tissue from paired, orientated eyes were fixed in 4% paraformaldehyde and mounted in protective plastic. Medium- to wide-angle diffraction at BMC-14 BioCARS (APS, Chicago, IL) with a 200 μm diameter, 0.9 Angstrom wavelength beam and 40 cm detector distance was performed on serial sections along the optic nerve. Fibrillar and molecular packing functions were measured from 1-D slices of the X-Ray scattering patterns, after background subtraction and calibration to hydrated rat tail tendon. The degree of anisotropy and relative abundances were determined from the scattering intensity and distribution plots. Results: Distinct X-Ray scattering patterns were observed. Equatorially oriented fibrillar packing functions (and molecular packing functions) of the left and right eye optic nerve sections corresponding to the region of unmyelinated axons and lamina cribrosa were 39 Angstroms (15.25 Angstroms) and 41.5 Angstroms (15.25 Angstroms). The fibrillar packing function increased and the molecular packing function decreased thereafter in the distal myelinated sections. The fibrillar packing functions (and molecular packing functions) measured sequentially in these sections distal to the lamina cribrosa in the right eye were 46, 46, 44, and 44 Angstroms (and 11, 11, 10.2, and 10.6 Angstroms). In comparison, the scleral molecular packing functions were 14.6 Angstroms and 14.5 Angstroms in samples from the left and right eyes. Conclusions: Wide-angle X-Ray scattering to determine the fibril and molecular packing functions and organization in the optic nerve and sclera is feasible as demonstrated here. These data indicate that the fibrillar packing function is smaller and the molecular packing function is larger at the level of the lamina cribrosa relative to distal regions along the optic nerve. Mapping the fibrillar ultrastructure of the optic nerve and surrounding sclera opens a new field of exploration. Ultrastructural changes within these connective tissues can be examined with similar X-Ray scattering techniques to correlate any changes occurring with vision loss and the effects of age, race, disease. CR: J.R. Lewis, None; K.M. Meek, None; J.P.R.O. Orgel, None. Support: None Copyright 2009 by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any abstract, contact the ARVO Office at [email protected]. Commercial Relationships are noted at the end of each abstract by “None” or with codes. 5666-5668