Natural history of individuals with retinal degeneration due to biallelic mutations in the RPE65 gene

Poster Details

First Author: B.Leroy BELGIUM

Co Author(s):    K. Reape   D. Chung   J. Wellman   E. Liu   K. High   T. Study Group              

Abstract Details


With recent advances in gene-based and other therapies, the need exists for greater understanding of the progression of inherited retinal disease (IRD) due to mutations in the RPE65 gene. 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.


Retrospective chart review including 7 worldwide tertiary referral centres.


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. These 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 colour vision and 65 (93%) had refractive errors, with the majority being myopic. Nystagmus was present in 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 exists and the optimal therapeutic window is unknown; however, therapeutic intervention (prior to extensive retinal degeneration) for IRDs due to RPE65 mutations has the potential to alter the progressive natural history of this disease.

Back to previous
EURETINA, Temple House, Temple Road, Blackrock, Co Dublin. | Phone: 00353 1 2100092 | Fax: 00353 1 2091112 | Email:

Privacy policyHotel Terms and Conditions Cancellation policy