ARVO 2016 Annual Meeting Abstracts 544 Mendelian Retinal Diseases Thursday, May 05, 2016 11:00 AM–12:45 PM Exhibit/Poster Hall Poster Session Program #/Board # Range: 6585–6601/D0356–D0372 Organizing Section: Retinal Cell Biology Program Number: 6585 Poster Board Number: D0356 Presentation Time: 11:00 AM–12:45 PM Novel RS1 Mutation in an Irish X-Linked Retinoschisis Cohort Kirk Stephenson1, Matthew Carrigan2, Paul Kenna3, 2, G Jane Farrar2, David Keegan1. 1Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland; 2Trinity College Dublin, Dublin, Ireland; 3Ophthalmology, Royal Victoria Eye & Ear Hospital, Dublin, Ireland. Purpose: To describe the phenotype and genotype of a family cohort (observational study, n=6) of X-linked retinoschisis in an Irish population with a novel RS1 mutation. Methods: Patients were recruited as part of the Irish national genetic screening registry for inherited retinal degenerations. This screening program includes clinical history and examination with retinal imaging, electrophysiology, visual field testing and genetic analysis. Six patients (age 62y – 74y) were identified with X-linked retinoschisis (five brothers, one male first cousin). Next generation sequencing (NGS) was performed for each patient. Investigation into the family history revealed 5 grandsons and a further maternal male first cousin that are affected. Results: All had a history of visual acuity and colour vision disturbance from childhood. There was significant phenotypic variability between the six subjects. The youngest and least severely affected patient had one eye enucleated; the remaining eye had a normal macular appearance, with vitreous strands. The eldest and most severely affected patient had advanced macular atrophy. The four patients of intermediate age and severity had a more classic macular retinoschisis pattern of retinal splitting. NGS detected a novel RS1 gene mutation (X chromosome); this was a single base change (c.413C>A) in exon 5. This mutation had not been previously submitted to the Retinoschisis Consortium, but a different mutation at this codon (c.412A>G) has been describe, which leads to a deficiency of the retinoschisin protein. Conclusions: This family has a novel gene mutation in the RS1 gene with clinical retinoschisis. The next step is to investigate the male children of these patients’ daughters for retinoschisis and this RS1 mutation. We aim to collaborate with current research in the development of gene therapy for treatment of RS1 gene mutations. Those with more advanced macular atrophy will have limited potential for improvement; however, the primary beneficiaries of gene therapy are the younger generation. With early clinical and genetic detection of X-linked retinoschisis phenotype/genotype in genetically predisposed individuals, permanent central visual loss may be prevented. Commercial Relationships: Kirk Stephenson, None; Matthew Carrigan, None; Paul Kenna, None; G Jane Farrar, None; David Keegan, None

Program Number: 6586 Poster Board Number: D0357 Presentation Time: 11:00 AM–12:45 PM Mutations in Receptor Expression Enhancing Protein 6 (REEP6) Cause Early Onset RP in Humans Smriti Agrawal1, 2, Aiden Eblimit1, 2, Feng Wang1, 2, Mingchu Xu1, 2, Kerry Goetz3, Yumei Li1, 2, Rui Chen1, 2. 1Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; 2Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX; 3Ophthalmic Genetics and Visual Function Branch, National Eye Institute/National Institutes of Health, Bethesda, MD. Purpose: Retinitis pigmentosa is a genetically heterogeneous disorder characterized by rod photoreceptor degeneration and is a leading cause of blindness worldwide. Currently, the genetic basis of about 40% of autosomal recessive (arRP) patients remains unknown. Here we report the identification and characterization of REEP6 (Receptor Expression Enhancing Protein 6) as a novel diseasecausing gene associated with arRP. Methods: Whole exome sequencing (WES) was performed on a cohort of unassigned RP patients previously screened with retinal capture sequencing for mutations in known disease-genes. To test the pathogenicity of the mutation identified in the patient, we used CRISPR/Cas9 mediated targeting to generate knock-in mice carrying the patient mutation. Immunohistochemistry was performed to examine expression and localization of the protein in the retina. To study retinal function, we performed scotopic and photopic retinal electroretinography (ERG). Optical Coherence Tomography (OCT), histological analysis, and immunohistochemistry were performed to further characterize morphological defects. Results: WES data analysis led to the identification of bi-allelic mutations in REEP6 in a patient with early-onset arRP. To confirm the pathogenicity of the patient mutation, we generated corresponding CRISPR-targeted knock-in mice. Immunostaining of WT retina confirmed the previously reported expression of Reep6 specifically in the outer segment (OS) of the rod photoreceptors, the outer nuclear layer (ONL), and the outer plexiform layer (OPL). Consistent with the phenotypes observed in the patient, Reep6 mutant mice exhibit progressive retinal degeneration with abnormal scotopic ERG response starting at 3 months of age, indicative of progressive rod dysfunction. OCT and histological analysis of Reep6 mutant mice show significant thinning of the ONL and photoreceptor degeneration. Conclusions: This study is the first to identify mutations in REEP6 that cause retinitis pigmentosa in humans. Furthermore, we have developed Reep6 knock-in mice that model the human disease, enabling us to gain insights into Reep6 dysfunction in photoreceptor degeneration. Our results suggest that Reep6 plays an important role in preserving proper photoreceptor function and survival. Commercial Relationships: Smriti Agrawal, None; Aiden Eblimit, None; Feng Wang, None; Mingchu Xu, None; Kerry Goetz; Yumei Li, None; Rui Chen, None Support: NEI Grant R01EY022356 and R01EY018571, Foundation Fighting Blindness Grant BR-GE-0613-0618-BCM Program Number: 6587 Poster Board Number: D0358 Presentation Time: 11:00 AM–12:45 PM Natural History of the Central Structural Abnormalities in Choroideremia: Insights from a Cross-sectional Study Anastasia Traband, Nicole Fuerst, Leona Serrano, Grace K. Han, Denise Pearson, Katherine Uyhazi, Jessica I. Morgan, Jean Bennett, Albert M. Maguire, Tomas S. Aleman. Ophthalmology, Scheie Eye Institute, Philadelphia, PA. Purpose: To increase understanding of the retinal structure and function in choroideremia (CHM).

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ARVO 2016 Annual Meeting Abstracts Methods: Patients with CHM, ages 6 to 71 years were evaluated by ocular examination. Retinal imaging was performed with spectral domain optical coherence tomography (SD-OCT) and near infrared reflectance (NIR-REF). SD-OCT cross sections were quantified along the horizontal meridian and related in a subset of patients to NIR-REF images and co-localized visual thresholds measured with automated static perimetry. Results: Eighty nine patients carrying the diagnosis of CHM were included. Youngest patients showed abnormalities of the photoreceptor outer segment (OS) - retinal pigmented epithelium (RPE) interdigitation layers, outer nuclear layer (ONL) thinning and central rod photoreceptor dysfunction. Most patients retained visual acuities better than 20/40 until the fifth decade of life. Visual acuity decline coincided with the approximation to the foveal center of transitional zones (TZs) of structural change from relatively preserved or thickened retina to severe thinning accompanied by vision loss. Photoreceptor loss was associated with a remodeling response that included thickening, the presence of interlaminar bridges and the formation of tubular structures. The lateral extent of the outer retinal sublaminae approximated the extent of relative preservation of RPE melanin by NIR-REF imaging. RPE disease generally paralleled or followed photoreceptor degeneration although there were frequent examples of photoreceptor survival in regions with severe RPE depigmentation and thinning of the choroid. Conclusions: Early CHM showed photoreceptor OS-apical RPE abnormalities. There was preservation of the central retinal function and structure until relatively late in the course of the disease. Proximity of TZs to the foveal center and the presence of a structurally disorganized or thin fovea heralded central vision loss. The results have implications for the planning of future gene therapy trials that intend to target the central retina. Commercial Relationships: Anastasia Traband; Nicole Fuerst, None; Leona Serrano, None; Grace K. Han, None; Denise Pearson, None; Katherine Uyhazi, None; Jessica I. Morgan, US Patent 8226236 (P), Canon, Inc. (F); Jean Bennett, Astellas Pharmaceuticals (R), Spark Therapeutics (S), Avalanche Technologies (R), Gunsight Biologics (S); Albert M. Maguire, Spark Therapeutics (S); Tomas S. Aleman, None Program Number: 6588 Poster Board Number: D0359 Presentation Time: 11:00 AM–12:45 PM The Natural History of Disease Progression in Patients With RPE65-Mediated Inherited Retinal Dystrophies Daniel C. Chung1, Jennifer Wellman1, Emily Liu1, Kathy Reape1, Julie Pappas2, Okan Elci2, Sarah McCague3, Katherine High1. 1Spark Therapeutics, Inc, Philadelphia, PA; 2Westat, Philadelphia, PA; 3 Children’s Hospital of Philadelphia, Philadelphia, PA. Purpose: Mutations in the Retinal Pigmented Epithelium 65 gene (RPE65) result in progressive visual deterioration, leading to blindness. These mutations are associated with an early-onset form of disease, Leber congenital amaurosis type 2, and a later-onset form, retinitis pigmentosa type 20, as well as various forms of Early-Onset Retinal Dystrophy (EORD). This study evaluates the natural history of visual acuity (VA) and kinetic visual field (VF) sensitivity over time, as well as the diverse diagnoses these patients receive. Methods: This was a global, retrospective, descriptive chart review study. Eligibility criteria included confirmatory genetic testing for biallelic RPE65 mutations, ≥2 office/clinic visits, and no other retinal pathology. Retrospective clinical data through anonymized patient records, noting VA, kinetic VF sensitivity and diagnosis at each clinic/ office visit were collected. Mixed-effects linear regression models were used to examine the effect of age on VA and kinetic VF sensitivity.

Results: Of 48 eligible subjects, 42 subjects with recorded VAs (age range 2-30 years) were identified, and VAs were converted to a LogMAR. Age and LogMAR scores were positively related, showing deteriorating VA over time. Mixed-effects linear regression model shows a statistically significant effect of age on VA (PA; N=36, 9-75y) were associated with

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ARVO 2016 Annual Meeting Abstracts normal (ERG group 1, N=18) or abnormal (ERG group 2 or 3, N=18) ERG with amplitudes outside the nCI in 31/36 cases. The 18 cases with normal ERGs were younger than those with retinal dysfunction (avg. 28 vs. 43 years, pC, and previously identified and novel deep-intronic variants on mRNA splicing, were analysed by reverse transcription (RT)-PCR of PPC mRNA and by in vitro assays with minigene constructs. Results: Haloplex sequencing revealed rare deep-intronic variants which potentially activate cryptic splice sites in 10 cases. Eleven STGD1 or arCRD patient-derived fibroblasts and two controls were reprogrammed into iPSCs and differentiated into PPCs. The c.546110T>C variant was shown to result in skipping of exon 39 or exon 39/40 in PPCs, effectively resulting in a null allele. PPC mRNA analysis provided preliminary evidence for abnormal RNA splicing due to deep-intronic variants. Conclusions: The c.5461-10T>C variant was shown to completely inactivate ABCA4 function, which renders it the most frequent severe ABCA4 variant. Locus sequencing, minigene splice assays and RT-PCR analysis of PPCs revealed several variants that potentially disrupt ABCA4 mRNA splicing. Commercial Relationships: Silvia Albert, None; Riccardo Sangermano, None; Nathalie Bax, None; Miriam Bauwens, None; Ingeborgh Van Den Born, None; Elfride De Baere, None; Alejandro Garanto, None; Rob Collin, None; Carel C. Hoyng, None; Frans P. Cremers, None

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ARVO 2016 Annual Meeting Abstracts Program Number: 6591 Poster Board Number: D0362 Presentation Time: 11:00 AM–12:45 PM Mutant Bestrophin-1 (BEST1) is degraded via the endolysosomal pathway Andrea Milenkovic, Bernhard H. Weber. Institute of Humangenetics, University of Regensburg, Regensburg, Germany. Purpose: Bestrophin-1 (BEST1), an integral membrane protein in the basolateral aspect of the RPE, is thought to act as a volume-regulated anion channel. Mutations in BEST1 cause Best vitelliforme macular dystrophy (BVMD) and are assumed to give rise to trafficking problems prompting the protein to remain within so far undefined cellular compartments. The precise molecular pathomechanisms of the disease-associated mutations are still unclear. Methods: Protein half-life was determined in polarized MDCKII cell lines, constitutively expressing wildtype BEST1 and seven diseaseassociated mutants. Cultivated cells were treated with cycloheximide (CHX, 20µg/ml) and harvested at various time points. Protein lysates were analyzed by densitometry of Western blot signals. To examine degradation pathways, cells were treated with CHX and a series of inhibitors for the proteasomal, lysosomal and autophagy pathway. BEST1 was localized by immunocytochemistry. Results: Normal BEST1 and BEST1-R218C revealed localization to the plasma membrane (PM) in contrast to intracellular localization of BEST1 mutants T6P, L21V, W93C, L224M, Y227N and F305S. Protein level of wildtype BEST1 remains stable even after 24h CHX treatment and arrest of protein synthesis, whereas six out of seven mutants degraded within 3 hours and mutant R218C within 12h. Similar to the majority of integral PM proteins, wildtype BEST1 is degraded via the endo-lysosomal pathway, inhibited by ammonium chloride (20mM) and chloroquine (10µM). Unexpectedly, all mutants tested do not reveal degradation via the proteasomal but instead via the endo-lysosomal degradation pathway. Consequently, low temperature (26°C) for 36h failed to foster trafficking of mutant BEST1 protein to the cell surface as described for many endoplasmic reticulum (ER)-retained mutants. Conclusions: Our data support the hypothesis that loss of BEST1 function is caused by a decrease in mutant protein stability with instable, temperature-insensitive mutant BEST1 degraded via the endo-lysosomal pathway. As a consequence, a chaperon-mediated rescue as shown for many mutants in disorders like CFTR, Parkinson Disease and Alzheimer disease may not lead to success in BVMD. Commercial Relationships: Andrea Milenkovic, None; Bernhard H. Weber, None Program Number: 6592 Poster Board Number: D0363 Presentation Time: 11:00 AM–12:45 PM Complement reactivity in Stargardt macular degeneration Jane Coffman1, Gayle J. Pauer2, Stephanie A. Hagstrom2, Mary E. Rayborn2, Joe G. Hollyfield2, Dean Bok1, Vera L. Bonilha2, Roxana A. Radu1. 1Ophthalmology, UCLA, Los Angeles, CA; 2 Cleavland Clinic, Cole Eye Institute, Cleveland, OH. Purpose: Stargardt macular degeneration (STGD) is a central blinding disease of children and young adults caused mostly by mutations in the ABCA4 gene. The proposed role of ABCA4 is to facilitating the clearance of all-trans-retinaldehyde from photoreceptor outer-segment disc membranes following a photobleach. The pathological hallmark of STGD is deposition of fluorescent vitamin A-containing pigments in cells of the retinal pigment epithelium (RPE). Phenotypic features of the Abca4/- mouse, the STGD model, include RPE lipofuscin-bisretinoid accumulation, followed by complement dysregulation, and loss of photoreceptor cells. Bisretinoid-dependent complement activation was previously reported in cultured fetal human RPE cells but has

never been studied in the context of the RPE of a STGD patient. Here, we evaluate the complement system in the donor eyes of STGD patients. Methods: Eyes were obtained through the FFB eye donor program. The patients were clinically diagnosed as STGD based on the symptoms and ocular changes. STGD donor #1 (66 y.o) had two ABCA4 mutations; ABCA4 genotype for STGD donor #2 (69 y.o) is unknown. Fixed perimacular and peripheral tissue samples of STGD and normal eyes (84 y.o.) were processed for immunohistochemistry using specific antibodies to C5b-9 (membrane attack complex, MAC), C3b/iC3b, and complement factor H (CFH). Results: STGD eyes showed increased thickness of Bruch’s membrane (BM) in the perimacular region in comparison to the control eyes. The deposition of MAC was indicated by significant C5b-9 immunoreactivity between BM and broken RPE basolateral membranes and also in the RPE cells. In contrast, the control eye showed C5b-9 immunoreactivity primarily in the choriocapillaris endothelium beneath an intact BM and little to none in the RPE. Pixel intensity quantification of MAC deposition was about 1.8-fold higher in STGD eye #2 compared to the control eye. C3 breakdown fragments were also observed within the RPE cells. We measured about 1.3-fold increase of C3b/iC3b level in the STGD eye compared to the control. However, CFH immunoreactivity appears similar between STGD and control eyes. Conclusions: Preliminary data suggest that, like the RPE of the Abca4-/- mouse, STGD human RPE cells are also dysfunctional as they lose their ability to suppress chronic insult by the complement system. Further analyses are directed toward characterization of complement reactivity using STGD patient-derived RPE cells. Commercial Relationships: Jane Coffman, None; Gayle J. Pauer, None; Stephanie A. Hagstrom, None; Mary E. Rayborn, None; Joe G. Hollyfield, None; Dean Bok, None; Vera L. Bonilha, None; Roxana A. Radu, None Support: NIH/NEI EY025002; Stein Eye Institute Core Grant NIH/ NEI EY000331 Program Number: 6593 Poster Board Number: D0364 Presentation Time: 11:00 AM–12:45 PM Long-term Follow-up of Autosomal Dominant Stargardt Macular Dystrophy (STGD3) Subjects Enrolled in a Fish Oil Supplement Interventional Trial Rene Choi, Aruna Gorusupudi, Paul S. Bernstein. Ophthalmology, Moran Eye Center - University of Utah, Salt Lake City, UT. Purpose: Autosomal dominant Stargardt macular dystrophy (STGD3) is a rare form of Stargardt disease secondary to mutations in the ELOVL4 gene. Mutations in ELOVL4 disrupt the pathways of synthesis of very-long chain polyunsaturated fatty acids (VLCPUFAs) from eicosapentaenoic acid (EPA) and arachidonic acid (AA). We have previously reported that members of a large Utah family with a two base-pair deletion in ELOVL4 who regularly consume fish have a much milder phenotype than those who rarely eat fish. Based on this observation, we asked whether fish oil supplementation could slow the course of STGD3. Methods: We enrolled 11 Utah STGD3 patients in a 7-year openlabel, clinical interventional study of over-the-counter fish oil supplements at a recommended dose of 650 mg of EPA and 350 mg of DHA per day (NCT00420602). Subjects had annual eye examinations with complete imaging, visual function testing, multifocal electroretinograms, and blood lipid analyses. Results: Compliance with the recommended fish oil supplement intervention was quite variable as assessed by patient self-report and by serum and red blood cell biomarkers of lipid consumption. Thus, even without randomization, we could divide the subjects into

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ARVO 2016 Annual Meeting Abstracts high supplementation and low supplementation groups. All subjects showed progression of their maculopathy over the course of the study, and we could not discern a beneficial effect of the intervention. Conclusions: Our inability to detect a benefit of fish oil supplementation in our cohort of STGD3 patients could be the result of small subject numbers or of intervention too late in the course of the disease. We still advise STGD3 patients to consume fish or fish oil regularly, and we recommend that pre-symptomatic children with ELOVL4 mutations should be especially targeted for these interventions. Commercial Relationships: Rene Choi, None; Aruna Gorusupudi, None; Paul S. Bernstein, None Support: Research to Prevent Blindness Clinical Trial: NCT00420602 Program Number: 6594 Poster Board Number: D0365 Presentation Time: 11:00 AM–12:45 PM Autosomal recessive bestrophinopathy – clinical and functional features Karsten Hufendiek1, 2, Herbert Jaegle2, Britta Fiebig3, 4, Carsten Framme1, Agnes B. Renner2. 1Ophthalmology, Hannover Medical School, Hannover, Germany; 2Ophthalmology, University Clinic Regensburg, Regensburg, Germany; 3Human genetics, Prenatal Care Center Hamburg, Hamburg, Germany; 4Human genetics, University of Regensburg, Regensburg, Germany. Purpose: Autosomal recessive bestrophinopathy (ARB) is a rare retinal dystrophy first described by Schatz et al. in 2006. The term ARB was introduced by Burgess et al. in 2008. ARB is caused by biallelic mutations in the BEST1 gene and is characteristically associated with multiple yellowish lesions (subretinal deposits) scattered at the posterior pole reaching the periphery, cystoid macular edema and subretinal fluid. So far, several single case reports and few families with ARB were reported. We present clinical and functional features of three unrelated individuals with ARB, and in one case a 5-year follow-up. Methods: Retrospective analysis of the clinical and electrophysiological data of three patients with ARB, including complete ophthalmological examination, fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), fullfield electroretinogram (ERG), multifocal ERG, electrooculogram (EOG), and molecular genetic analysis of the BEST1 gene. Results: We present the data of three female patients, who were 3-, 24-, and 50-years of age, respectively, at first visit in our clinic. Funduscopy revealed in all cases central irregularities and atrophy of the retinal pigment epithelium (RPE), multiple yellowish lesions at the posterior pole, often small and round in shape and scattered along the vascular arcades and peripapillary. FAF was increased in areas corresponding to the yellowish lesions and reduced in areas of RPE defects. OCT of the macula detected in two cases subretinal fluid, irregularities of the photoreceptor outer segments, and in one case a distinct cystoid edema. Best corrected visual acuity ranged between 0.8 and 0.1 (Snellen chart). Full-field ERG was normal in the youngest, only mildly reduced in the middle, and markedly reduced in the oldest patient. EOG, tested in one case, showed absence of the light rise. In all three patients, two heterozygous BEST1 mutations were identified. During the 5-year follow-up in one patient, the yellowish lesions changed their size, number and arrangement at the posterior pole whereas visual acuity was stable. Conclusions: Autosomal recessive bestrophinopathy is a rare disease, which can manifest already in early childhood. It shows a characteristic phenotype including yellowish lesions, which change their appearance during the course of the disease. Typical findings in

FAF and OCT enhance finding the diagnosis and allow for a detailed follow-up. Commercial Relationships: Karsten Hufendiek, None; Herbert Jaegle, None; Britta Fiebig, None; Carsten Framme, None; Agnes B. Renner, None Program Number: 6595 Poster Board Number: D0366 Presentation Time: 11:00 AM–12:45 PM Phenotypic Progression of a Discordant Stargardt Disease in a Large Consanguineous Tunisian Family: Longitudinal Follow-up Leila El Matri1, 2. 1Ophthalmology, Hedi Rais Institute, Tunis, Tunisia; 2Oculogenetic laboratory LR14SP01, Tunis, Tunisia. Purpose: To assess the clinical 9 years phenotype progression of Stargardt (STGD) disease caused by a new ABCA4 mutation in a large Tunisian family. Methods: Seven accessible members from two related families were followed up for 9 years. A detailed clinical examination was performed for all subjects at each control. DNA from patients was analyzed for ABCA4 mutations using multiplex ligation-dependent probe amplification (MLPA). Results: At presentation, 4 different retinal phenotypes were observed. Phenotype 1: Bull’s eye maculopathy and slightly altered photopic responses in full field electroretinography observed in the youngest child of the family A. Phenotype 2: macular atrophy and white-yellow flecks in two brothers. Phenotype 3: diffuse macular, peripapillary and peripheral RPE atrophy and hyperfluorescent dots in 2 sisters. Phenotype 4: Two cousins in family B displayed Stargardt disease-fundus flavimaculatus phenotype. After 9 years progression, all the 7 patients displayed progression toward phenotype 3 with advanced stage of STGD and a diffuse atrophy. Genetic analysis showed ABCA4 mutation: (?-4635)_ (5714+?)dup; (?-6148)_(6479-?) del Conclusions: This is a report on phenotypic progression of STGD disease in a large Tunisian family. First, different phenotypes were displayed with a clinical intra and interfamilial variation. After 9 years follow-up, all patients showed the same phenotypic evolution confirming the progressive nature of the disease. The reported mutation has not been already described; phenotypic analysis and screening for causative mutations might be helpful in confirming the precise diagnosis and contributes towards a better categorization and prognosis. Commercial Relationships: Leila El Matri Program Number: 6596 Poster Board Number: D0367 Presentation Time: 11:00 AM–12:45 PM Macular morphology and function in patients with ABCA4 related retinal degeneration Edoardo Abed1, Lucia Galli-Resta2, Giorgio Placidi1, Francesca Campagna1, Benedetto Falsini1. 1Ophthalmology, Catholic University, Rome, Italy; 2CNR, Pisa, Italy. Purpose: To assess the correlation between macular function and morphology in patients with ABCA4-related retinal degenerations (ABCA4-RD). Methods: Thirty-three patients with ABCA4-RD were enrolled in this retrospective case series. The diagnosis of ABCA4-RD was clinically established and confirmed, in all cases, by genetic testing. Examination protocol included visual acuity (BCVA) measurement, indirect ophthalmoscopy, optical coherence tomography (OCT) and focal electroretinogram (FERG) from the central 18 degrees according to a published protocol (Falsini et al., IOVS, 2000). Photoreceptors loss was estimated by measuring the linear extension of the interruption of photoreceptors inner/outer segments (IS/OS) junction. Macular thickness (MT) and foveal thickness (FT) were

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ARVO 2016 Annual Meeting Abstracts calculated by OCT software as the mean retinal thickness in two circular areas, centered at the fovea, of 6 and 1 mm of diameter respectively. Twenty age-matched healthy patients were also enrolled and served as controls for FERG. Results: FERG amplitude was significantly reduced in patients with ABCA4-RD compared with controls (p