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CRB1-associated Retinal Dystrophies: Genetics, Clinical Characteristics and Natural History

Varela, Malena Daich; Georgiou, Michalis; Alswaiti, Yahya; Kabbani, Jamil; Fujinami, Kaoru; Fujinami-Yokokawa, Yu; Khoda, Shaheeni; ... Michaelides, Michel; + view all (2022) CRB1-associated Retinal Dystrophies: Genetics, Clinical Characteristics and Natural History. American Journal of Ophthalmology 10.1016/j.ajo.2022.09.002. (In press). Green open access

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Abstract

PURPOSE: To analyse the clinical characteristics, natural history, and genetics of CRB1-associated retinal dystrophies. DESIGN: Multicenter international retrospective cohort study. METHODS: Review of clinical notes, ophthalmic images, and genetic testing results of 104 patients (91 probands) with disease-causing CRB1 variants. Macular optical coherence tomography (OCT) parameters, visual function, fundus characteristics, and associations between variables were our main outcome measures. RESULTS: The mean age of the cohort at the first visit was 19.8 ± 16.1 (median 15) years of age, with a mean follow-up of 9.6 ± 10 years. Based on history, imaging, and clinical examination, 26 individuals were diagnosed with retinitis pigmentosa (RP, 26%), 54 with early-onset severe retinal dystrophy/Leber Congenital Amaurosis (EOSRD/LCA, 51%), and 24 with macular dystrophy (MD, 23%). Severe visual impairment was most frequent after 40 years of age for patients with RP and after 20 years of age for EOSRD/LCA. Longitudinal analysis revealed a significant difference between baseline and follow up best corrected visual acuity in the three sub-cohorts. Macular thickness decreased in most patients with EOSRD/LCA and MD, whereas the majority of patients with RP had increased perifoveal thickness. CONCLUSIONS: A subset of individuals with CRB1 variants present with mild, adult-onset RP. EOSRD/LCA phenotype was significantly associated with null variants, and 167_169 deletion was exclusively present in the MD cohort. The poor OCT lamination may have a degenerative component, as well as being congenital. Disease symmetry and reasonable window for intervention highlight CRB1 retinal dystrophies as a promising target for trials of novel therapeutics.

Type: Article
Title: CRB1-associated Retinal Dystrophies: Genetics, Clinical Characteristics and Natural History
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ajo.2022.09.002
Publisher version: https://doi.org/10.1016/j.ajo.2022.09.002
Language: English
Additional information: This work is licensed under an Attribution 4.0 International License (CC BY 4.0).
Keywords: CRB1, Early Onset Severe Retinal Dystrophy, LCA, RP, fundus autofluorescence, gene therapy, genotype, macular dystrophy, optical coherence tomography, phenotype, retinal dystrophy
UCL classification: 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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10156028
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