Loss of Function of RIMS2 Causes a Syndromic Congenital Cone-Rod Synaptic Disease with Neurodevelopmental and Pancreatic Involvement.

Congenital cone-rod synaptic disorder (CRSD), also known as incomplete congenital stationary night blindness (iCSNB), is a non-progressive inherited retinal disease (IRD) characterized by night blindness, photophobia, and nystagmus, and distinctive electroretinographic features. Here, we report bi-allelic RIMS2 variants in seven CRSD-affected individuals from four unrelated families. Apart from CRSD, neurodevelopmental disease was observed in all affected individuals, and abnormal glucose homeostasis was observed in the eldest affected individual. RIMS2 regulates synaptic membrane exocytosis. Data mining of human adult bulk and single-cell retinal transcriptional datasets revealed predominant expression in rod photoreceptors, and immunostaining demonstrated RIMS2 localization in the human retinal outer plexiform layer, Purkinje cells, and pancreatic islets. Additionally, nonsense variants were shown to result in truncated RIMS2 and decreased insulin secretion in mammalian cells. The identification of a syndromic stationary congenital IRD has a major impact on the differential diagnosis of syndromic congenital IRD, which has previously been exclusively linked with degenerative IRD.

GENETICS OF LARGE PIGMENT EPITHELIAL DETACHMENTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We hypothesized that severe forms of neovascular age-related macular degeneration (AMD) such as large pigment epithelial detachments poorly responding to anti-vascular endothelial growth factor therapy might present a distinct genotype compared with overall series of neovascular AMD. METHODS: This is a multicenter genetic association study. Sixty-eight patients presenting pigment epithelial detachments resistant to ranibizumab (issued from ARI2 study, register number NCT02157077 on clinicaltrials.gov) were compared with two series of patients derived from previously published clinical studies, presenting neovascular AMD (NAT2 study n = 300 and PHRC study n = 1,127), and with healthy controls (n = 441). The phenotype of neovascular AMD groups was based on visual acuity measurement, fundus examination, spectral-domain optical coherence tomography, and angiographic data. All samples were genotyped for three single-nucleotide polymorphisms: CFH (rs1061170), ARMS2 (rs10490924), and C3 (rs2230199). Significant difference in allele frequency between participants with neovascular AMD and control was the main outcome measurement. RESULTS: The GG genotype of the C3 rs2230199 was significantly more frequent in the ARI2 group (55.9%) than the PHRC group (6.0%, P < 0.0001; odds ratio = 24.0 [95% confidence interval 10.4-55.0]) and the NAT2 group (5.1%, P < 0.0001; odds ratio = 16.1 [95% confidence interval 5.0-51.9]). The repartition of patients carrying a T allele of the ARMS2 (rs10490924) or patients carrying a C allele of the CFH (rs1061170) was similar in the ARI2 group when compared with the NAT2 and PHRC groups. CONCLUSION: In our series, the genotype GG of C3 rs2230199 was more significantly associated with the phenotype of large vascularized pigment epithelial detachment poorly responding to anti-vascular endothelial growth factor therapy than in global AMD series.

TWO-YEAR FOLLOW-UP OF A RETINAL ASTROCYTIC HAMARTOMA IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To report a case of retinal astrocytic hamartoma imaged by optical coherence tomography angiography (OCTA), followed for 2 years. METHODS: Observational case report. RESULTS: A 25-year-old woman was referred for an incidental retinal lesion in the left eye (LE). At baseline, the best-corrected visual acuity in the LE was 20/32, and fundus examination showed the presence of a round, pigmented lesion in juxtafoveal region, corresponding, on spectral domain OCT, to a hyperreflective lesion within nerve fiber layer. Optical coherence tomography angiography revealed the presence of a high-flow lesion in the superficial capillary plexus segmentation. The patient was followed up for 2 years: best-corrected visual acuity remained stable and multimodal imaging, including OCTA, confirmed the benign and stable nature of the lesion. At baseline, the total lesion area on OCTA (superficial capillary plexus) was 0.181 mm2, whereas vascular density was 52.080%; the total area was 0.204 mm2, and vascular density was 53.740% at 2-year follow-up. CONCLUSION: Optical coherence tomography angiography is helpful not only for the diagnosis and follow-up of such rare tumors, but also it gives insights as to how these tumors develop and how they affect surrounding structures.

A case of undiagnosed X-linked retinoschisis presenting as unilateral macular demarcation line.

PURPOSE: We intend to describe an uncommon presentation of X-linked juvenile retinoschisis (XLRS) in a 17-year-old boy showing a macular demarcation line in the right eye and an inferior peripheral bullous retinoschisis in both right and left eye, at his first ophthalmologic examination. METHODS: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity assessment, anterior segment and dilated fundus examination, ultra-wide-field retinography, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, electroretinography, visual field test, and genetic molecular testing. RESULTS: We report a rare case of genetically confirmed XLRS, presenting as a unilateral mildly-pigmented macular demarcation line (advanced sequel of unilateral spontaneous retinal reattachment of a previous retinal detachment or bullous retinoschisis) without foveoschisis in the fellow eye. CONCLUSION: XLRS is the most frequent cause of macular retinoschisis. The hallmark of XLRS is the evidence of a foveoschisis presenting with a characteristic spoke-wheel aspect in patients younger than 30 years of age. It is important to recognize uncommon presentations of XLRS so that the correct diagnosis is made, in order to provide the patients with appropriate genetic counseling and therapeutic care.

Optical coherence tomography angiography findings of choroidal neovascularization secondary to laser injury: A case report.

PURPOSE: To report a case of choroidal neovascularization (CNV) secondary to laser injury imaged by optical coherence tomography angiography (OCTA) and treated by intravitreal anti-vascular endothelial growth factor (VEGF). OBSERVATIONS: A 14-year-old boy presented with vision loss and central scotoma in the right eye (RE) in the last month, after having stared at the beam of a laser pointer. At presentation, his best-corrected visual acuity (BCVA) in the RE was 20/40 and spectral-domain OCT (SD-OCT) showed an interruption of ellipsoid zone and the presence of an hyperrelfective lesion in subfoveal region. OCTA examination revealed the presence of a high-flow lesion on both outer retina to choriocapillaris (ORCC) and choriocapillaris segmentations. The patient was treated by one anti-VEGF injection: at one month follow-up his BCVA in the RE was 15/20. SD-OCT revealed the complete resolution of hyperreflective lesion and no detectable flow on OCTA. CONCLUSIONS AND IMPORTANCE: Retinal laser injury may be complicated by CNV. OCTA may non-invasively assess the presence of CNV, as well as treatment-response.

Sensitivity and Specificity of Ultrawide-Field Fundus Photography for the Staging of Sickle Cell Retinopathy in Real-Life Practice at Varying Expertise Level.

PURPOSE: To evaluate the sensitivity and specificity of ultrawide-field fundus photography (UWF-FP) for the detection and classification of sickle cell retinopathy (SCR) by ophthalmologists with varying degrees of expertise in retinal disease. METHODS: Patients presenting with sickle cell disease (SCD) in the Créteil University Eye Clinic, having undergone UWF-FP and ultrawide-field fluorescein angiography (UWF-FA) on the same day, were retrospectively included. Eyes with previous retinal photocoagulation were excluded. SCR was graded independently by UWF-FP and UWF-FA using Goldberg classification by two ophthalmologists with varying expertise levels. RESULTS: Sixty-six eyes of 33 patients were included in the study. The sensitivity of UWF-FP for the detection of proliferative SCR was 100%, (95% confidence interval [CI95%] 76.8-100) for the retinal specialist and 100% (CI95% 71.5-100) for the ophthalmology resident. The specificity of UWF-FP for the detection of proliferative SCR was 100% (CI95% 92.7-100) for the retinal specialist and 98.1% (CI95% 89.7-100) for the ophthalmology resident. CONCLUSIONS: UWF-FP is a valuable exam for proliferative SCR screening, with excellent sensitivity and specificity and a good inter-grader agreement for ophthalmologists with various degree of skills, and is easy to use in a real-life setting.