The effect of human gene therapy for RPE65-associated Leber’s congenital amaurosis on visual function: a systematic review and meta-analysis

BACKGROUND: RPE65-associated LCA (RPE65-LCA) is an inherited retinal degeneration caused by the mutations of RPE65 gene and gene therapy has been developed to be a promising treatment. This study aims to evaluate the association between changes in visual function and application of gene therapy in patients with RPE65-LCA. METHODS: Several databases (PubMed, Cochrane Library, and Web of Science) were searched for results of studies describing efficacy of gene therapy in patients with RPE65-LCA. Six studies, which included one randomized and five prospective non-randomized clinical trials, 164 eyes met our search criteria and were assessed. RESULTS: The BCVA significantly improved in treated eyes at 1 yr post treatment by − 0.10 logMAR (95% CI, − 0.17 - -0.04; p = 0·002), while there was no significant difference at 2–3 years post treatment (WMD: 0.01; 95% CI, − 0.00 - 0.02; p = 0·15). FST sensitivity to blue flashes also improved by 1.60 log (95% CI, 0.66–2.55; p = 0.0009), but no significant difference to red flashes (WMD: 0.86; 95% CI, − 0·29–2.01; p = 0.14) at 1 yr. There was no significant difference in central retinal thickness at 1 yr, but central retina in treated eyes appeared thinner at 2–3 years post treatment by 19.21 μm (95% CI, − 34.22 - -4.20; p = 0.01). CONCLUSIONS: Human gene therapy is a pioneering treatment option for RPE65-LCA. Although its efficacy appears to be limited to less than 2 yrs after treatment, it carries the potential for further improvement and prolongation of efficacy.