• Pediatric Ophth/Strabismus

    This prospective study found that gene therapy for Leber congenital amaurosis caused by RPE65 mutations is sufficiently safe and substantially efficacious in the extrafoveal retina. However, the authors say that there is no benefit and some risk to treating the fovea.

    The authors examined the safety and efficacy of subretinal gene therapy for the RPE65 form of Leber congenital amaurosis using recombinant adeno-associated virus 2 (rAAV2) carrying the RPE65 gene in 15 patients aged 11 to 30 years. All patients underwent subretinal injection of the rAAV2-RPE65 vector into the worse-functioning eye. There were five cohorts representing four dose levels and two injection strategies.

    Visual function improved in all patients to varying degrees, with improvements localized to treated areas. Cone and rod sensitivities increased significantly in the study eyes but not the control eyes. Minor acuity improvements were recorded in many study and control eyes. Major acuity improvements occurred in study eyes, with the lowest entry acuities and parafoveal fixation loci treated with subretinal injections. Some patients with better foveal structure lost retinal thickness and acuity after subfoveal injections.

    The authors detected no systemic toxicity and identified no ocular adverse events related to surgery. No evidence of age-dependent effects was found.

    They recommend not including the fovea in macular subretinal injections except when there is foveal atrophy (determined by OCT) or very reduced visual acuity and fixation is parafoveal (readily detectable on OCT scans). They say this approach also opens the door to the treatment of patients at later disease stages when there is foveal atrophy but a preserved extrafoveal outer nuclear layer.