Centripetal Retinal Degeneration Follows an Exponential Decay and May Be Reversed Following Gene Therapy

Abstract

Purpose: To model the progression of the hyperautofluorescent ring in rod-cone dystrophies and to report a novel finding of its reversal following gene therapy. Design: Retrospective analysis of a prospective cohort study. Participants: Fifty-eight individuals with genotyped rod-cone dystrophies and hyperautofluorescent rings on fundus autofluorescence. Methods: Patients with a rod-cone dystrophy and hyperautofluorescent rings on fundus autofluorescence were identified and their rings categorized according to disease progression. Correlation between fundus autofluorescence and optical coherence tomography parameters in patients with early-mid stage disease were calculated. A retrospective longitudinal analysis of fundus autofluorescence images was subsequently performed. Results: The internal ring diameter, external ring diameter, and ring thickness were strongly correlated with ellipsoid zone width, external limiting membrane width, and loss of the ellipsoid zone respectively. Longitudinal analysis suggested that fundus autofluorescence changes decline predictably in a logarithmic fashion. Results indicated significant reversal of the hyperautofluorescent ring following RPGR gene therapy, correlating with improvements in retinal sensitivity. Conclusions: Centripetal retinal degeneration in rod-cone dystrophies follows an exponential decay and gene therapy may reverse both structural and functional deficits.