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Purpose: To report the retinal phenotype in 2 patients simulating type 2 macular telangiectasis with new variants in CYP2U1 implicated in hereditary spastic paraplegia type 56 (HSP 56). Design: Cross sectional case series study. Participants: Five members of a non-consanguineous family (parents and 3 male children) were investigated. Methods: All family members underwent a full ophthalmic evaluation and multimodal retinal imaging. Two family members demonstrating retinal anomalies underwent additional OCT angiography, dual wavelength autofluorescence and fluorescence lifetime imaging ophthalmoscopy, kinetic perimetry, fundus-correlated microperimetry, electroretinography, and electro-oculography. Whole-exome sequencing was performed in all 5 family members. Main Outcome Measures: To characterize the retinal phenotype in affected patients with variants in CYP2U1, using multimodal imaging: dual-wavelength autofluorescence, fluorescence lifetime, OCT angiography. Results: The 2 siblings with compound heterozygous novel variants c.452C>T; p.(Pro151Leu), c.943C>T; p.(Gln315Ter) in CYP2U1 demonstrated parafoveal loss of retinal transparency and hyperreflectivity to blue light, redistribution of macular pigment to the parafoveal edge, photoreceptor loss, and fluorescence lifetime imaging ophthalmoscopy anomalies: a pattern compatible with that seen in macular telangiectasia type 2 (MacTel). One had manifest neurological abnormalities since early childhood; the second had no neurological abnormalities. Each parent and the third sibling were heterozygous for 1 variant and were neurologically and ophthalmically normal. Conclusions: These CYP2U1 variants are associated with a retinal phenotype very similar to that otherwise specific for MacTel, suggestive of possible links in the etiology and pathogenesis of these diseases. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Introduction: The GNB1 (guanine nucleotide-binding protein, β1) gene encodes for the ubiquitous β1 subunit of heterotrimeric G proteins, which are associated with G-protein-coupled receptors (GPCRs). GNB1 mutations cause a neurodevelopmental disorder characterized by a broad clinical spectrum. A novel variant has recently been confirmed in a case of rod-cone dystrophy. Case Presentation: We describe the second confirmed case of a classical rod-cone dystrophy associated with a mutation located in exon 6 of GNB1 [NM_002074.5:c.217G>C, p.(Ala73Pro)] in a 56-year-old patient also presenting mild intellectual disability, attention deficit/hyperactivity disorder, and truncal obesity. Conclusion: This paper confirms the role of GNB1 in the pathogenesis of a classic rod-cone dystrophy and highlights the importance of including this gene in the genetic analysis panel for inherited retinal diseases.

Abstract Background As the trend of refractive lens exchange for presbyopia continues to grow, our case report shows the first occurrence of an acute bilateral outer retinopathy following uncomplicated sequential clear lens extraction in an otherwise healthy individual. Case presentation A 54-year-old male without significant medical history benefited from a sequential bilateral lens exchange for presbyopia. He then experienced a rapid vision loss in both eyes, accompanied by photopsias and myodesopsias, with symptoms appearing respectively 4 and 3 weeks after the surgeries. Multimodal imaging revealed a fulminant outer retinopathy, leading to a total loss of light perception within a few days. Immediate intravenous corticosteroid therapy was administered, permitting to recover a small area of central visual function in both eyes, enabling shape and color distinction. The primary diagnostic hypothesis is a presumed autoimmune retinopathy, triggered by the cataract extraction, while an alternative diagnosis could be a toxic reaction secondary to the use of intracameral cefuroxime and lidocaine during the surgery. Conclusion In this report, the authors describe the first recorded instance of outer retinopathy following cataract surgery. This occurrence raises the possibility of auto-immunization leading to retinal atrophy and vision loss as a potential outcome after undergoing cataract surgery.

Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies.Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases.Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.