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Kathleen Z Reape, Daniel C Chung, Grace Schaefer, Jennifer A. Wellman, Emily Liu, Julie Pappas, Okan Elci, Sarah McCague, Katherine A High; Natural History of Individuals with Retinal Degeneration Due to Biallelic Mutations in the RPE65 Gene. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1488.
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© ARVO (1962-2015); The Authors (2016-present)
With recent advances in gene-based and other therapies, the need exists for greater understanding of the progression of RPE65-mediated inherited retinal disease (IRD). A retrospective chart review of 70 individuals with IRD associated with confirmed biallelic mutations in the RPE65 gene was conducted to elucidate the natural history of the disease.
Clinical data, including visual acuity (VA), visual field (VF), optical coherence tomography (OCT), and other vision parameters, as well as background information (demographics, ocular history and examination, genetic and clinical diagnoses) were collected and analyzed from charts at seven tertiary referral centers worldwide. VA and VF data were presented previously; ocular findings are presented here.
Statistically significant effects of age on VA (p<0.001) and Goldmann VF (p<0.0001) were observed. On OCT, no statistically significant age effect on foveal or outer nuclear layer thickness was observed although data were limited. On ocular history, 74% reported orientation and/or mobility issues and 80% reported use of low vision aids. More than half reported poor night vision, and more than 90% had a clinical diagnosis or onset of symptoms by the age of 18. Sixty subjects (86%) had some abnormality in color vision and 65 (93%) had refractive errors, with the majority being myopic. Nystagmus was present in almost 80%, and was not always accompanied by a clinical diagnosis of Leber congenital amaurosis. Approximately 20% had cataracts or lens abnormalities. Other structural abnormalities, while variable, generally appeared to increase with age, consistent with progressive retinal degeneration.
Despite limitations inherent in the retrospective design, this study provides important natural history information regarding the clinical course of the disease. Clinical findings, along with the heterogeneity in clinical diagnoses and genetic mutations support the need for genetic testing. Clear age-related declines in VA and VF, as well as structural abnormalities were observed, with no evidence of spontaneous, sustained improvement. Variability is high and the optimal therapeutic window is unknown, however therapeutic intervention (prior to extensive retinal degeneration) for RPE65-mediated IRD has the potential to alter the progressive natural history of this disease.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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