LCA associated with RPE65 is a complex disease in which vision loss results from two pathological mechanisms—dysfunction and degeneration of photoreceptors.25, 26 The accumulation of all-trans retinyl esthers has a toxic effect, causing progressive degeneration of both rod and cone photoreceptors, and resulting in profound visual impairment by early adulthood.29 As the disease process is secondary to a lack of the wild-type protein, gene therapy aimed at augmenting RPE65 gene expression was an obvious therapeutic target. The gene discussed is RPE65; the disease is Leber congenital amaurosis.