The Effect of Age on Gene Therapy Efficacy for RPE65 Leber’s Congenital Amaurosis: A Pooled Analysis

Abstract

- Leber’s congenital amaurosis (LCA) is an inherited retinal disease that leads to severe vision loss from birth. Gene therapy for LCA caused by mutations in the RPE65 gene has been discovered to be a promising treatment, and one treatment (Luxturna) has received FDA approval. Within the current body of clinical trials, there is little consensus on whether age has any effect on treatment efficacy and outcomes. This pooled analysis aims to discern the effect of age on changes in visual function in patients undergoing adeno-associated virus mediated gene therapy for RPE65-LCA. The PubMed database was searched for papers describing the results of RPE65 gene therapy on patients with LCA, and data were pooled from 5 selected studies. Linear regression of age on percent change from baseline visual acuity in treated eyes was conducted on the pooled data from one, two, and three years post-treatment. Linear regression of age on change from baseline retinal thickness in treated eyes was conducted on the pooled data at one year post-treatment. At 1 year, a s tatistically significant linear regression equation of age versus visual acuity was found (α = 0.05, n = 78, F(1, 76) = 7.3152, p = 0.0084). At the same time point, a statistically significant linear regression equation of age versus change in r etinal thic kness was not found (α = 0.05, n = 50, F(1, 48) = 0.07756, p = 0.7818). Age appears to be a statistically significant predict or of improvements in visual acuity, but not of retinal degeneration. Younger age appears to be associated with greater improvements in vision. However, the age predictive effect is only visible in the first year after treatment, and may be attributed to the decline in long-term data availability. Future analysis using a larger sample size is needed to evaluate the effect after one year.