Leber Congenital Amaurosis Caused by an RPGRIP1 Mutation Shows Treatment Potential

Purpose To determine the treatment potential in Leber congenital amaurosis (LCA) resulting from an RPGRIP1 (retinitis pigmentosa GTPase regulating–interacting protein 1) mutation, a form of LCA with recent gene therapy success in an animal model. Design Case report of a rare genetic eye disease investigated for intervention potential. Participants A 19-year-old man with LCA. Methods We studied the retinal structure and function in an LCA patient with a novel homozygous Val1211Glu mutation in the RPGRIP1 gene using optical coherence tomography and colocalized dark-adapted thresholds. Main Outcome Measure Optical coherence tomography results. Results Central retinal laminar architecture was preserved, and there was a measurable outer nuclear layer. The retained retinal structure corresponded to the region of visual sensitivity. With increasing eccentricity, there was no measurable visual function, and retinal laminar disorganization suggested a remodeling process. Conclusions The RPGRIP1 -LCA patient has treatment potential for a gene replacement strategy if targeted to central, but not pericentral or peripheral, retina. The results differ from similarly studied RPE65 -LCA and CRB1 -LCA patients. Preclinical progress toward therapy in LCA patients warrants detailed structure-function studies in humans to determine feasibility and candidacy for clinical trials.