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.