Leber congenital amaurosis due to gucy2d mutations: Longitudinal analysis of retinal structure and visual function

Abstract

Gene augmentation therapy is being planned for GUCY2D‐associated Leber congenital amaurosis (LCA). To increase our understanding of the natural history of GUCY2D‐LCA, patients were evaluated twice with an interval of 4 to 7 years between visits using safety and efficacy outcome measures previously determined to be useful for monitoring this disorder. In this group of molecularly‐identified LCA patients (n = 10; ages 7–37 years at first visit), optical coherence tomog-raphy (OCT) was used to measure foveal cone outer nuclear layer (ONL) thickness and rod ONL at a superior retinal locus. Full‐field stimulus testing (FST) with chromatic stimuli in dark‐ and light-adapted states was used to assay rod and cone vision. Changes in OCT and FST over the interval were mostly attributable to inter‐visit variability. There were no major negative changes in structure or function across the cohort and over the intervals studied. Variation in severity of disease expression between patients occurs; however, despite difficulties in quantifying structure and function in such seriously visually impaired individuals with nystagmus, the present work supports the use of OCT as a safety outcome and FST as an efficacy outcome in a clinical trial of GUCY2D‐LCA. A wide age spectrum for therapy was confirmed, and there was relative stability of structure and function during a typical time interval for clinical trials.