AAV-mediated Gene Therapy

AAV gene therapy for RPE65-associated LCA showed significant improvements in visual acuity and full-field stimulus testing at 1 year, but these gains were not sustained at 2–3 years. One gene therapy review found only minimal gains in visual acuity and mobility, but moderate improvements in full-field stimulus testing. Voretigene neparvovec (AAV2-mediated gene replacement) has produced durable visual improvements in RPE65-associated LCA when sufficient retinal cells remain. Gene therapy was the most frequently studied advanced approach because many IRDs are caused by specific genetic mutations. Evidence for visual acuity improvement and adverse events in RPE65-associated LCA gene therapy was graded high, supporting strong confidence in efficacy and safety for those outcomes. AAV gene therapy demonstrated reassuring safety results and evidence of therapeutic effect across 80 clinical trials. Surgery required to deliver gene therapy still carries risks, so safety outcomes are not risk-free.