UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

RBP3-retinopathy - inherited high myopia and retinal dystrophy: Genetic Characterization, Natural History, and Deep Phenotyping

Georgiou, Michalis; Fujinami, Kaoru; Robson, Anthony G; Fujinami-Yokokawa, Yu; Shakarchi, Ahmed F; Ji, Marco H; Uwaydat, Sami H; ... Michaelides, Michel; + view all (2023) RBP3-retinopathy - inherited high myopia and retinal dystrophy: Genetic Characterization, Natural History, and Deep Phenotyping. American Journal of Ophthalmology 10.1016/j.ajo.2023.09.025. (In press). Green open access

[thumbnail of 1-s2.0-S0002939423004063-main.pdf]
Preview
Text
1-s2.0-S0002939423004063-main.pdf - Accepted Version

Download (1MB) | Preview

Abstract

Objective: To examine the genetic and clinical features and the natural history of RBP3-associated retinopathy. // Design: Multi-center international, retrospective, case series. // Setting: Three tertiary referral centers. // Participants: Adults and children, with molecularly confirmed RBP3-associated retinopathy. // Main Outcomes and Measures: Multi-center, international, retrospective, consecutive observational study in three tertiary referral centers of adults and children, with molecularly confirmed RBP3-retinopathy. The genetic, clinical and retinal imaging findings, including optical coherence tomography (OCT) and fundus autofluorescence (FAF), were investigated both cross-sectionally and longitudinally. The results of International standard full-field and pattern electroretinography (ERG; PERG) were reviewed. // Results: We ascertained 12 patients (5 females), from 10 families, with four patients previously reported. Eight novel disease-causing RBP3 variants were identified. Ten patients were homozygous. The mean age (±SD, range) of the group was 21.4 years (±19.1, 2.9-60.5 years) at baseline evaluation. All 12 patients were highly myopic with a mean spherical equivalent of -16.0D (range; -7.0D to -33.0D). Visual acuity was not significantly different between eyes and no significant anisometropia was observed. Mean best corrected visual acuity (BCVA) was 0.48 LogMAR (range; 0.2-1.35, SD; ± 0.29 LogMAR) at baseline. Eleven patients had longitudinal BCVA assessment, with a mean BCVA of 0.46 LogMAR after a mean follow-up of 12.6 years. All patients were symptomatic with reduced VA and myopia by the age of 7 years. All patients had myopic fundi and features in keeping with high myopia on OCT, including choroidal thinning. The 4 youngest patients had no fundus pigmentary changes, with the rest presenting with a variable degree of mid-peripheral pigmentation and macular changes. FAF showed variable phenotypes, ranging from areas of increased signal to advanced atrophy in older patients. OCT showed cystoid macular edema at presentation in three patients, which persisted during follow-up in two patients and resolved to atrophy for the third patient. The ERGs were abnormal in 9 of 9 cases, revealing variable relative involvement of rod and cone photoreceptors with additional milder dysfunction post-phototransduction in some. All but one had PERG evidence of macular dysfunction, severe in most. // Conclusions: This study details the clinical and functional phenotype of RBP3-retinopathy in the largest cohort reported to date. RBP3-retinopathy is a disease characterized by early onset, slow progression over decades, and high myopia. The phenotypic spectrum and natural history as described herein has prognostic and counselling implications. RBP3-related disease should be considered in children with high myopia and retinal dystrophy.

Type: Article
Title: RBP3-retinopathy - inherited high myopia and retinal dystrophy: Genetic Characterization, Natural History, and Deep Phenotyping
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ajo.2023.09.025
Publisher version: https://doi.org/10.1016/j.ajo.2023.09.025
Language: English
Additional information: Creative Commons Attribution (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/).
Keywords: RBP3 retinopathy, RBP3, retinal dystrophy, interphotoreceptor binding protein, high myopia, genetics, genotype, phenotype, retina
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10179330
Downloads since deposit
6Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item