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

Summary

This is a study published in the American Journal of Ophthalmology. The study looked at people with a type of inherited retina disease called rod-cone dystrophy. The authors measured a bright ring seen on eye scans and found that it usually gets smaller in a very steady way over time. They also found that after gene therapy, this ring may get bigger again, which suggests the treatment may help the retina work better.

Keywords: rod-cone dystrophy, retinal degeneration, gene therapy, eye scans, retina, disease progression.

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 (FAF).

Methods

Patients with a rod-cone dystrophy and hyperautofluorescent rings on FAF were identified and their rings categorized according to disease progression. Correlation between different FAF and optical coherence tomography (OCT) parameters in patients with early-mid stage disease were calculated. A retrospective, longitudinal analysis of FAF images was subsequently performed. A linear mixed model, with the dependent variable of total horizontal hyperautofluorescent ring width and independent variables of time, genotype and the interactions was used.

Main Outcome Measures

Horizontal diameter of the hyperautofluorescent ring.

Results

A total of 58 rod-cone dystrophy patients were analyzed in this study. Twenty eyes of 20 patients presented with early to mid-stage disease. The internal ring diameter, external ring diameter and ring thickness, were strongly correlated with the ellipsoid zone width (r = 0.94), external limiting membrane width (r = 0.97) and loss of the ellipsoid zone (r = 0.92) respectively. Longitudinal analysis suggests that FAF changes decline very predictably in a logarithmic fashion (R2 = 0.958). Results indicated a significant reversal of the hyperautofluorescent ring following RPGR gene therapy (using Cotoretigene Toliparvovec), correlating with improvements in retinal sensitivity.

Conclusions

Our findings suggest that centripetal retinal degeneration in rod-cone dystrophies follows an exponential decay and that gene therapy may reverse both structural and functional deficits.