Mutations in SAMD7 cause autosomal-recessive macular dystrophy with or without cone dysfunction.

Sterile alpha motif domain containing 7 (SAMD7) is a component of the Polycomb repressive complex 1, which inhibits transcription of many genes, including those activated by the transcription factor Cone-Rod Homeobox (CRX). Here we report bi-allelic mutations in SAMD7 as a cause of autosomal-recessive macular dystrophy with or without cone dysfunction. Four of these mutations affect splicing, while another mutation is a missense variant that alters the repressive effect of SAMD7 on CRX-dependent promoter activity, as shown by in vitro assays. Immunostaining of human retinal sections revealed that SAMD7 is localized in the nuclei of both rods and cones, as well as in those of cells belonging to the inner nuclear layer. These results place SAMD7 as a gene crucial for human retinal function and demonstrate a significant difference in the role of SAMD7 between the human and the mouse retina.

Anti-Vascular Endothelial Growth Factor Treatment in Diabetic Macular Edema-Results from a Large Single Center Cohort with Bevacizumab As First-Line Therapy.

PURPOSE: To explore visual acuity (VA) outcomes of anti-vascular endothelial growth factor (VEGF) intravitreal injections in treatment-naive eyes with diabetic macular edema (DME), with bevacizumab as first-line treatment. METHODS: Retrospective single-center cohort study over a three-year follow-up. 1765 eyes from 1179 patients treated with intravitreal injections were evaluated. The cohort was divided according to the treatment given: (1) bevacizumab monotherapy, (2) eyes switched to 2nd line agent, and (3) eyes switched to a 3rd line agent. RESULTS: 644 eyes of 444 patients met inclusion criteria. Mean age at presentation was 64.0±11.1 years. Mean follow-up period was 24.6±12.4 months. 67.1% of eyes were treated with bevacizumab monotherapy, 25.45% switched to a 2nd line agent, and 7.45% were switched to a 3rd line agent. Mean number of injections decreased significantly during each treatment year in the total cohort and within each treatment group (P<0.001). Mean VA for the total cohort and within each treatment group improved significantly throughout follow-up (P<0.001). No significant difference in VA found between the groups (P=0.373). CONCLUSIONS: This real-world study demonstrates robust and consistent VA gains over long-term follow-up in eyes with DME treated with either bevacizumab monotherapy or switching to alternative anti-VEGF agents in cases of suboptimal response.

POLYPOIDAL LESIONS ASSOCIATED WITH CHOROIDAL NEVI.

PURPOSE: To investigate eyes with polypoidal lesions associated with choroidal nevi, their multimodal imaging characteristics, and long clinical follow-up. METHODS: Multicenter, retrospective case series study of patients with polypoidal lesions overlying choroidal nevi. Demographic and clinical information were recorded. Multimodal imaging including color fundus photography, optical coherence tomography, optical coherence tomography angiography, fundus fluorescein angiography, indocyanine angiography, and A- and B-scan ultrasonography were analyzed for nevus and polypoidal lesion characteristics. RESULTS: Fourteen eyes (14 patients; mean age: 70.3 ± 6.7 years) with polypoidal lesions overlying choroidal nevi were included. The mean follow-up duration was 50.0 ± 27.9 months (range 12-108). All nevi were pigmented on color fundus photography, flat on ultrasonography with a mean basal diameter of 3.8 ± 0.4 mm. In all but one eye, optical coherence tomography showed a shallow irregular pigment epithelium detachment overlying the nevus. A total of 11/14 eyes (78.6%) had exudative activity, 9 eyes received intravitreal anti-vascular endothelial growth factor injections, and one eye required intravitreal anti-vascular endothelial growth factor combined with photodynamic therapy. Mean visual acuity was 20/32 at baseline and 20/50 at final visit. CONCLUSION: We present the largest known cohort of eyes with polypoidal lesions associated with choroidal nevi with up to 9 years follow-up. The exudative degree of the polypoidal lesion in this condition is variable and treatment decisions should be taken on an individual basis. We hypothesize that choroidal ischemia because of altered choroidal vasculature rather than Haller layer hyperpermeability plays a role in the formation of polypoidal lesions overlying nevi.

Genetic causes of inherited retinal diseases among Israeli Jews of Ethiopian ancestry.

Purpose: This study sought to describe the phenotype frequency and genetic basis of inherited retinal diseases (IRDs) among a nationwide cohort of Israeli Jewish patients of Ethiopian ancestry. Methods: Patients' data-including demographic, clinical, and genetic information-were obtained through members of the Israeli Inherited Retinal Disease Consortium (IIRDC). Genetic analysis was performed by either Sanger sequencing for founder mutations or next-generation sequencing (targeted next-generation sequencing or whole-exome sequencing). Results: Forty-two patients (58% female) from 36 families were included, and their ages ranged from one year to 82 years. Their most common phenotypes were Stargardt disease (36%) and nonsyndromic retinitis pigmentosa (33%), while their most common mode of inheritance was autosomal recessive inheritance. Genetic diagnoses were ascertained for 72% of genetically analyzed patients. The most frequent gene involved was ABCA4. Overall, 16 distinct IRD mutations were identified, nine of which are novel. One of them, ABCA4-c.6077delT, is likely a founder mutation among the studied population. Conclusions: This study is the first to describe IRDs' phenotypic and molecular characteristics in the Ethiopian Jewish community. Most of the identified variants are rare. Our findings can help caregivers with clinical and molecular diagnosis and, we hope, enable adequate therapy in the near future.

Ocular injury from foam dart (Nerf) blasters: a case series.

To report clinical outcomes following ocular injury from foam dart (nerf) blasters - a spring-loaded toy guns that fire foam-coated darts or bullets at a relatively low velocity. These guns gained popularity in recent years among children and adolescents. Eleven patients with ocular injuries from foam dart blasters were included in this retrospective, single-center study. Visual acuity (VA), intraocular pressure (IOP), and anterior segment, glaucoma-related, and vitreoretinal complications were recorded at each visit. The average age at presentation was 13.4 years and 82% were male. Mean initial VA was 6/12 (range 6/6 - 1/18); On initial examination, nine patients (82%) had hyphema, three (27%) had corneal abrasions, three (27%) had vitreous hemorrhage, and two (18%) had traumatic mydriasis. Four patients (36%) experienced glaucoma-related complications, including three (27%) with angle recession and three (27%) with increased IOP. Three patients (27%) were diagnosed with posterior segment injuries, including three (27%) with commotio retinae and one (9%) with severe retinal photoreceptor damage. No patients required surgical intervention. CONCLUSION: Foam dart blasters can cause severe blunt ocular trauma and permanent visual loss, illustrating the need for eye protection when handling these toys. WHAT IS KNOWN: • Foam dart blasters, a blanket term for spring-loaded toy guns that fire foam-coated darts or bullets at a relatively low velocity, have gained popularity in recent years among pediatric populations, with an increase in associated ocular injuries. • To date, scattered case reporting provides insufficient insight into the full clinical spectrum of injury and prognosis of foam dart blasters related ocular injury. WHAT IS NEW: • This case series characterizes the myriad foam dart blasters injuries that may afflict the eye, most of which are self-limiting, but some of which may result in poor visual outcomes and lifelong disability in pediatric patients. • We strongly recommend that all users wear eye protection while using foam dart blasters.

Ten-year follow-up and sequential evaluation of multifocal retinal pigment epithelium abnormalities in central serous chorioretinopathy.

PURPOSE: The study aims to analyze the 10-year outcomes in "simple" and "complex" central serous chorioretinopathy (CSCR) and to evaluate the longitudinal changes in multifocal retinal pigment epithelium (RPE) alterations. METHODS: This was a retrospective, multicentric, longitudinal, observational study in patients with a diagnosis of CSCR. Visual acuity outcomes and recurrence characteristics of simple and complex were analyzed. Changes in number of foci of RPE alterations from baseline to last visit were evaluated. RESULTS: Out of 235 eyes screened, the study included 67 eyes of 39 patients (32 males and 7 females) with CSCR (12 simple and 55 complex CSCR). A total of 17 (29.9%) eyes had a unifocal RPE alteration, while the remaining 50 had multifocal RPE alterations at baseline. In eyes with complex CSCR, the 10-year visual acuity was significantly worse (p < 0.001), more number of eyes required treatment (p = 0.03), higher number of RPE alterations were present at baseline and last follow-up (p < 0.001 for both), and number of recurrences were higher (p < 0.001), than simple CSCR. Focal collections of RPE alterations and leakage site corresponded to mid-phase hyper-fluorescent plaques (MPHP) in all eyes. On multivariate regression analysis, a larger area of RPE alteration was associated with a worser 10-year visual acuity (p = 0.004) and complex CSCR was associated with higher number of recurrence (p = 0.005). CONCLUSION: A different course of disease progression was seen in simple and complex CSCR. An evolution in foci of RPE alterations was seen, from a simple area of MPHP, to focal RPE alterations and finally to leakage.

ACQUIRED VITELLIFORM LESIONS: A Novel Finding in Eyes with Peripapillary Pachychoroid Syndrome.

PURPOSE: To describe a novel finding of acquired vitelliform lesions in eyes with peripapillary pachychoroid syndrome. METHODS: A retrospective, multicenter, observational case series including seven patients with peripapillary pachychoroid syndrome and concomitant acquired vitelliform lesions. Medical records and multimodal imaging findings were comprehensively reviewed. RESULTS: Six of seven patients were men, with a mean age of 72.6 years. Mean baseline best-corrected visual acuity was 0.11 ± 0.07 (Snellen equivalent 20/25), and all patients presented with baseline best-corrected visual acuity of 20/30 or better. Mean follow-up time was 24.4 months (range 1-54 months). At last follow-up, best-corrected visual acuity was stable in 13/14 eyes, and deteriorated in one eye because of subfoveal atrophy.Fundus examination revealed peripapillary retinal pigment epithelium alterations and pigment migration in all eyes. Fundus autofluorescence showed mottled hyperautofluorescence and hypoautofluorescence in the peripapillary region, and hypoautofluorescent lesions corresponding to the pigmentary changes. Optical coherence tomography showed nasal choroidal thickening and pachyvessels with overlying retinal pigment epithelium irregularity. All eyes presented with peripapillary intraretinal fluid. Subretinal fluid was present in five eyes of three patients. Acquired vitelliform lesions were present in 11 eyes. CONCLUSION: The novel association between peripapillary pachychoroid syndrome and acquired vitelliform lesions is characterized by the classic findings of both entities, and visual prognosis is accordingly good.

IMPACT OF COVID-19 PANDEMIC LOCKDOWNS ON VISUAL ACUITY OF PATIENTS WITH NEOVASCULAR AMD: A Large Cohort.

PURPOSE: Evaluating the impact of delayed care, secondary to coronavirus disease 2019 (COVID-19) pandemic lockdowns, on visual acuity in previously treated neovascular age-related macular degeneration (nAMD) patients. METHODS: This was a multicenter, retrospective, study of patients with nAMD previously treated with anti-VEGF injections who were followed up during 2019 (pre-COVID-19) and compared with patients with nAMD during 2020 (COVID-19). RESULTS: A total of 1,192 patients with nAMD with a mean age of 81.5 years met the inclusion criteria. Of these, 850 patients were assessed in 2019 (pre-COVID-19) and 630 patients were assessed in 2020 (COVID-19). Three hundred eight patients were assessed through both 2019 and 2020 and thus were included in both cohorts. There was no significant difference between 2020 and 2019 in baseline and change in best-corrected visual acuity (BCVA; P = 0.342 and P = 0.911, respectively). The mean number of anti-VEGF injections was significantly lower (5.55 vs. 6.13, P < 0.01), with constant lower ratio of injections per patient in the COVID-19 period. Baseline BCVA (0.859, P < 0.01), number of injections (-0.006, P = 0.01), and age (0.003, P < 0.01) were predictors of final BCVA. CONCLUSION: In patients with nAMD, delayed care secondary to COVID-19 pandemic lockdowns has no statistically significant impact on BCVA. Best-corrected visual acuity, older age, and lower number of yearly anti-VEGF injections are predictors for decrease BCVA.

FLUID-BASED VISUAL PROGNOSTICATION IN TYPE 3 MACULAR NEOVASCULARIZATION-FLIP-3 STUDY.

PURPOSE: To analyze the effect of fluid on visual acuity in cases of Type 3 macular neovascularization. METHODS: This multicentric, retrospective cohort study included eyes with treatment-naïve Type 3 macular neovascularization. Analysis of fluid in different compartments was performed. Group A included eyes with isolated intraretinal fluid, whereas Group B included eyes with intraretinal fluid in conjunction with subretinal fluid and/or sub retinal pigment epithelial fluid. RESULTS: Eyes in Group A (31, 55.3%) had better best-corrected visual acuity of 20/50 snellen equivalent (0.42 ± 0.31 logarithm of the minimum angle of resolution) at baseline and 20/50 snellen equivalent (0.40 ± 0.28 logarithm of the minimum angle of resolution) at complete resolution compared with Group B with visual acuity of 20/80 snellen equivalent (0.64 ± 0.35 logarithm of the minimum angle of resolution) (P = 0.0181) at baseline and 20/100 snellen equivalent (0.70 ± 0.40 logarithm of the minimum angle of resolution) (P = 0.0021) at complete resolution. Subfoveal atrophy was more in Group B (82.6% 19/23) at complete resolution in comparison to Group A (16/31, 51.6%). Eyes in Group B needed more anti-vascular endothelial growth factor injections (10.3 ± 9.0) for complete resolution compared with Group A (5.7 ± 4.8). CONCLUSION: Intraretinal fluid may be associated with good visual acuity in Type 3 macular neovascularization in contrast to other forms of neovascular age related macular degeneration. Furthermore, intraretinal fluid in isolation may need fewer injections and could probably be associated with less subfoveal atrophy.

THE TARGET SIGN: A Near Infrared Feature and Multimodal Imaging in a Pluri-Ethnic Cohort with RDH5-Related Fundus Albipunctatus.

PURPOSE: Retinol dehydrogenase 5 (RDH5)-related fundus albipunctatus can present with phenotypic variability. Our purpose was to investigate new clinical characteristics and multimodal imaging findings in patients from different ethnic origins, carrying different mutations. METHODS: Multicenter international retrospective case series of 18 patients with genetically confirmed RDH5-related fundus albipunctatus. Patients' files were reviewed for fundus images, visual acuity, macular optical coherence tomography scans, near-infrared images, fundus autofluorescence, electroretinogram, and genetic mutations. Imaging and electroretinogram findings. RESULTS: All eyes (n = 36, 100%) showed small circular findings seen on near-infrared images, termed as the "target sign," correlating to the yellowish dots seen clinically and to the distinct hyperreflective linear lesions on optical coherence tomography at the level between external limiting membrane and retinal pigment epithelium. Perifoveal atrophy with foveal sparing was seen in 4 eyes of 2 patients (both RDH5-c.160C>T, p.R54X mutation). Fundus autofluorescence revealed small hyperautofluorescent dots (n = 16, 44.4%). Scotopic electroretinograms were significantly reduced in all cases with an electronegative pattern, 66.7% displayed cone dysfunction. CONCLUSION: Our results show distinct imaging findings present in all patients with fundus albipunctatus independent of ethnicity or genetic mutation. Our results can facilitate the current algorithm to diagnose RDH5-related fundus albipunctatus and allow for targeted genetic testing.

The Effect of Syringe-Filling Technique on the Risk for Endophthalmitis after Intravitreal Injection of Anti-VEGF Agents.

PURPOSE: This study aimed to compare the risk for post-injection endophthalmitis between different anti-vascular endothelial growth factor (VEGF) agents and syringe preparation techniques. METHODS: A retrospective study of anti-VEGF injections performed in 3 large ophthalmology departments between 2013 and 2019 was conducted. Injections were categorized according to the drug and the syringe-filling technique - prefilling by a hospital pharmacy, prefilling by a good manufacturing practice (GMP) pharmacy, self-drawing from the vial by the injecting physician, and use of a prefilled syringe. Cases of endophthalmitis were identified, and their rates were analyzed. RESULTS: A total of 197,402 injections were included, and 53 cases of endophthalmitis were identified (0.027% risk). The risk of endophthalmitis following injections with syringes that were prefilled by GMP pharmacies or the manufacturers was significantly lower than that following injections which were self-drawn by the physician (0.019% vs. 0.055%, p < 0.0001). For ranibizumab, risk of endophthalmitis decreased since it became available in a prefilled syringe (0.054% vs. 0.014%, p = 0.066), bordering on statistical significance. CONCLUSIONS: The syringe-filling technique is an important factor determining risk of post-injection endophthalmitis. Use of GMP-grade prefilling by professional pharmacies or the manufacturers significantly reduces this risk and should be the technique of choice for all drugs administered by intravitreal injection.

Is There a Dose-Response Relationship? Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Treatment in Neovascular Age-Related Macular Degeneration.

PURPOSE: The aim of study was to explore the dose-response relationship of anti-vascular endothelial growth factor (VEGF) agents, with bevacizumab as 1st-line treatment, on the visual-acuity (VA) outcome during the first year of treatment in neovascular AMD (nAMD) patients in real-life conditions. METHODS: This was a retrospective, observational, single-center study at the Ophthalmology Division, Tel Aviv Medical Center. Inclusion criterion was naive AMD patients treated with anti-VEGF injections between the years 2017-2020. Electronic medical records were scanned using the MDClone software, and data from time of diagnosis, containing baseline VA, final VA, number of injections, and the injected agent, were gathered. Subjects were divided into three groups based on their baseline VA ("good," "middle," and "low"). RESULTS: A total of 672 patients were included. The cohort demonstrated a statistically nonsignificant correlation with a positive trend between the log transformation of the number of annual injections and the change in VA (p = 0.145). However, a significant correlation was established within the "low-VA" group (p = 0.015). The "good-" and "middle-VA" groups did not reach statistical significance. Baseline VA was the single significant predictor for VA gain within patients with baseline VA of 6/12 or less. CONCLUSIONS: A dose-response relationship between anti-VEGF injections and the VA outcome was found only for patients with low baseline VA. Individual patient characteristics might need to be taken into account to customize treatment regimen and improve visual outcome.

Additive Value of a Face-to-Face Visit to Virtual Remote Decision in Patients with Neovascular Age-Related Macular Degeneration.

INTRODUCTION: The increasing high prevalence of neovascular age-related macular degeneration (nvAMD) in the aging population combined with the need for frequent monitoring and treatment for many years, especially in the COVID-19 era, raises the need to establish an effective, reliable, and safe follow-up and treatment model. This study evaluates the difference in treatment decisions comparing between the gold standard face-to-face clinical examination and virtual evaluation approach based only on visual acuity (VA) and optical coherence tomography (OCT) scans without clinical fundoscopic examination in nvAMD patients. METHODS: A single-center retrospective cohort study was conducted that compared an original "face-to-face" visit treatment decision regarding the need for anti-vascular endothelial growth factor drug, interval, and treatment regimen based on routine VA, spectral domain OCT imaging, and dilated fundus examination to two "virtual" treatment decisions based on evaluation of OCT scans and previous medical records before and after revealing VA data on the same nvAMD patients eyes. RESULTS: About 169 eyes of 114 patients were included in the study. Forty-nine patients (43%) suffered from bilateral nvAMD and had both eyes included in the study. Agreement between the "face-to-face visit treatment decision" and "virtual treatment decision" was noted in 74.6% and 71.6% eyes before and after revealing the patient's VA in the study visit, respectively. CONCLUSIONS: Virtual evaluation results in similar treatment decisions for nvAMD patients compared to standard face-to-face clinical examination.

MULTIPLE INTRAVITREAL INJECTIONS DO NOT CAUSE ANTERIOR SCLERAL THINNING: An Ultrasound Biomicroscopy Study.

PURPOSE: To evaluate possible changes in anterior scleral thickness and structure and changes in the anterior segment in eyes receiving multiple intravitreal injections using ultrasound biomicroscopy imaging. METHODS: Prospective, interventional, nonrandomized, cross-sectional study. Both eyes from 33 patients previously treated at least by 15 intravitreal injections in one eye only for retinal diseases were included. Intravitreal injections were performed by ophthalmologists using an aseptic standardized procedure. Ultrasound biomicroscopy examination was performed in all eyes, and scleral thickness was measured at the pars plana in four quadrants. Anterior chamber depth and ciliary body size were measured. Scleral thickness in the study eye was compared with the fellow eye. Secondary outcome measures were 1) anterior chamber depth; 2) ciliary body size; 3) scleral qualitative changes in the study eye compared with the fellow eye and 4) risk factors for scleral thinning. RESULTS: There was no statistically significant difference in scleral thickness between the study and fellow eyes when comparing each quadrant between the two eyes (P = 0.86 superotemporal; P = 0.76 superonasal; P = 0.72 inferonasal; P = 0.55 inferotemporal). Scleral thickness was neither related to the number of injections nor to the duration of treatment in the treated eye. CONCLUSION: Multiple intravitreal injections do not impact scleral thickness in a clinical practice using different injection sites.

Occlusive retinal vasculopathy with macular branch retinal artery occlusion as a leading sign of atypical hemolytic uremic syndrome - a case report.

BACKGROUND: Hemolytic Uremic Syndrome (HUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, considered within the group of thrombocytic microangiopathies. Ocular complications in HUS are very rare. Here, we report an adult patient who suffered from acute onset of paracentral scotoma, caused by branch retinal artery occlusion (BRAO), as a leading symptom of atypical HUS. CASE PRESENTATION: A 39-year-old healthy male was lately diagnosed with essential hypertension and mild renal impairment. He complained about acute onset of central scotoma in his left eye. Fundus examination revealed marked narrowing of retinal vessels, cotton wool spots and few retinal hemorrhages in both eyes. The patient was diagnosed with bilateral ischemic retinal vasculopathy and acute macular BRAO in his left eye. Workup revealed thrombocytopenia, worsening renal failure. Renal biopsy showed signs of chronic thrombotic microangiopathy. The patient was diagnosed with atypical HUS (aHUS) and started on plasmapheresis, together with eculizumab. As his condition continued to worsen, he was put on renal replacement therapy. Due to a persistent monoclone of IgG1, the patient underwent bone marrow biopsy which revealed Monoclonal Gammopathy of renal significance, triggering a HUS and treatment was initiated accordingly. Two months after initial presentation, the patient developed neovascularization of the optic disc (NVD) in his left eye, and was treated with 3 monthly intravitreal bevacizumab injections with complete regression of the NVD. The patient suffered from myocardial infarction in the later course and was lost for follow-up. He returned 11 months after the last bevacizumab injection because of sudden loss of vision in his left eye caused by a dense vitreous hemorrhage. Biomicroscopy revealed a new NVD in his right eye. The patient underwent panretinal photocoagulation in both eyes with regression of neovascularization. Vision improved and remained 20/20 in both eyes. CONCLUSION: We present a case report showing retinal ischemia can be linked with aHUS. As clinal diagnosis might be challenging, physicians should be aware of the rare ocular manifestations of this devastating multi-organ disease. In case of retinal ischemia, panretinal photocoagulation should be initiated soon to avoid blinding complications.

Standardization of Optical Coherence Tomography Angiography Imaging Biomarkers in Diabetic Retinal Disease.

Optical coherence tomography Angiography (OCT-A) represents a revolution in the noninvasive evaluation of retinal and choroidal circulation especially in detecting early clinical signs of diabetic retinal disease (DRD). With appropriate use, OCT-A characteristics and measurements have the potential to become new imaging biomarkers in managing and treating DRD. Major challenges include (a) provision of standardized outputs from different OCT-A instruments providing standardized terminology to correctly interpret data; (b) the presence of artifacts; (c) the absence of standardized grading or interpretation method in the evaluation of DRD, similar to that already established in fundus photography; and (d) establishing how OCT-A might be able to provide surrogate markers to demonstrate blood retinal barrier breakdown and vascular leakage, commonly associated with DRD. In fact, OCT-A guidelines for DRD are still evolving. The outputs of quantitative OCT-A data offer a unique opportunity to develop tools based on artificial intelligence to assist the clinicians in diagnosing, monitoring, and managing patients with diabetes. In addition, OCT-A has the potential to become a useful tool for the evaluation of cardiovascular diseases and different neurological diseases including cognitive impairment. This article written by the members of Diabetic Retinopathy expert committee of the European Vision Clinical Research network will review the available evidence on the use of OCT-A as an imaging biomarker in DRD and discuss the limits and the current application as well as future developments for its use in both clinical practice and research trials of DRD.

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC).

Inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptors. These diseases show marked phenotypic and genetic heterogeneity. The Israeli IRD consortium (IIRDC) was established in 2013 with the goal of performing clinical and genetic mapping of the majority of Israeli IRD patients. To date, we recruited 2,420 families including 3,413 individuals with IRDs. On the basis of our estimation, these patients represent approximately 40% of Israeli IRD patients. To the best of our knowledge, this is, by far, the largest reported IRD cohort, and one of the first studies addressing the genetic analysis of IRD patients on a nationwide scale. The most common inheritance pattern in our cohort is autosomal recessive (60% of families). The most common retinal phenotype is retinitis pigmentosa (43%), followed by Stargardt disease and cone/cone-rod dystrophy. We identified the cause of disease in 56% of the families. Overall, 605 distinct mutations were identified, of which 12% represent prevalent founder mutations. The most frequently mutated genes were ABCA4, USH2A, FAM161A, CNGA3, and EYS. The results of this study have important implications for molecular diagnosis, genetic screening, and counseling, as well as for the development of new therapeutic strategies for retinal diseases.

Multicolor imaging in macular telangiectasia-a comparison with fundus autofluorescence.

PURPOSE: To describe various clinical features of idiopathic juxtafoveal retinal telangiectasis group 2A or idiopathic macular telangiectasia type 2 (MacTel) on multicolor imaging (MCI) and compare imaging findings of MacTel on MCI with fundus autofluorescence (FAF). METHODS: Patients with a clinical diagnosis of MacTel based on Gass and Blodi's classification were included. FAF and MCI images were graded qualitatively for stage of disease, margins of involvement, hyperautofluorescence on FAF (corresponding retinal atrophy on MCI), and detection of crystals. FAF and MCI were graded quantitatively for the area and number of quadrants involved, hypoautofluorescene on FAF (corresponding intraretinal pigment hyperplasia or retinal pigment epithelium [RPE] atrophy on MCI), and foci of right-angled venules. RESULTS: Seventy-eight eyes of forty five patients were included with both imaging modalities showing no difference with respect to staging of non-proliferative MacTel. Retinal crystals were recognized on MCI but not on FAF. Neurosensory retinal atrophy and  subretinal neovascular membranes were detected using MCI with 92.3 and 83.3% sensitivity, respectively. Intraretinal pigmented hyperplasia was more accurately detected (70.1 vs 58.4%) compared with RPE atrophy on MCI. MCI showed larger area of involvement, higher number of quadrants involved (p < 0.001), and better delineation of margins (p = 0.002) compared with FAF. A higher mean number of vessel dipping foci was noted on MCI in comparison with FAF (3.34 vs 3.1). CONCLUSION: Various parameters were more easily defined using MCI compared with FAF which qualifies MCI as an enface depth-resolved imaging adjunct to conventional multimodal imaging in MacTel. The ability to detect enface as well as cross-sectional imaging features makes MCI a valuable tool in MacTel.

A NOVEL FINDING OF HYPERREFLECTIVE MATERIAL IN THE SILICONE-RETINA INTERFACE: An Optical Coherence Tomographic and Histopathological Study.

PURPOSE: To describe novel findings of hyperreflective material in the silicone-retina interphase on spectral domain optical coherence tomography (SD-OCT) imaging in eyes with silicone oil tamponade. METHODS: Retrospective observational clinical study of consecutive patients who underwent primary pars plana vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment. Repeat clinical examination and spectral domain optical coherence tomography macular imaging performed 3 months after surgery were evaluated to identify any macular pathologies, including formation of epiretinal membranes, intraretinal changes, subretinal fluid, and edema before scheduled secondary vitrectomy for silicone oil removal. RESULTS: Eighty-two patients (mean age 54 years, range 22-89) were included. Twelve eyes (14%) showed discrete preretinal hyperreflective organized coarse material in the silicone-retina interphase on spectral domain optical coherence tomography. The material was scattered in the posterior pole, with several foci showing additional hyperreflectivity of the inner retinal layers beneath. These findings did not resemble silicone oil emulsification in size, shape, or reflectivity. CONCLUSION: This is the first report on hyperreflective material detected by spectral domain optical coherence tomography in the silicone-retina interphase in eyes with silicone oil tamponade. These findings may represent an inflammatory response to silicone oil exposure that may be the initial manifestation of a future proliferative process, warranting a rigorous follow-up protocol for affected patients.

Visual function tests including the role of optical coherence tomography in neurofibromatosis 1.

Optic pathway glioma (OPG) is a common and significant complication of neurofibromatosis 1 (NF-1) that might lead to vision loss. The main reason to treat OPG is to preserve vision. Tumor location along the visual pathway largely dictates the presenting signs and symptoms. Clinical ophthalmic evaluation is focused on optic nerve functions including evaluation of pupils' reaction to light, visual acuity, color vision, and visual field, as well as optic nerve appearance. An important relatively new ancillary test is optic coherence tomography (OCT) that measures the volume of retinal nerve fiber layer around the optic nerve and the ganglion cell layer-inner plexiform layer (GCL-IPL) of the macula, both proved to be strongly associated with losing vision in OPG. Accurate evaluation of vision functions plays a critical role in the decision of treatment. In this review, we describe the ophthalmological assessment including new biomarkers in clinical use. We also outline prognostic factors and current recommendations for surveillance and indications for treatment.