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Updated: May 25, 2026
Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium
Published on: August 7, 2015
Centripetal Retinal Degeneration Follows an Exponential Decay and May Be Reversed Following Gene Therapy
Maram E A Abdalla Elsayed1, Amandeep S Josan1, Salwah Rehman1
1From the Nuffield Laboratory of Ophthalmology (M.E.A.A.E., A.S.J., S.R., R.E.M.), Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Oxford Eye Hospital (M.E.A.A.E., A.S.J., S.R., R.E.M.), Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
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.
