Efficacy and safety of AAV RPGR gene therapy in X-linked retinitis pigmentosa: a systematic review and meta-analysis

Abstract

X-linked retinitis pigmentosa (XLRP) represents a severe inherited retinal dystrophy associated with pathogenic variants in the retinitis pigmentosa GTPase regulator (RPGR) gene. Adeno-associated virus (AAV)-mediated RPGR gene augmentation is designed to preserve photoreceptor structure and function. The purpose of this study was to critically appraise and quantitatively synthesize the efficacy and safety evidence for AAV-RPGR gene therapy in X-linked retinitis pigmentosa. Scopus, PubMed, the Cochrane Library, ScienceDirect, and Google Scholar were searched from inception through July 11, 2026. Two reviewers independently screened records, two reviewers assessed risk of bias, and extracted data were verified by a second reviewer. Proportions were synthesized using inverse-variance fixed-effect logit models with a 0.5 continuity correction for zero or all-event cells; DerSimonian-Laird random-effects models were used as sensitivity analyses. Cohort linkage, dose-stratified safety, and overlap-adjusted analyses were performed. The search identified 571 records and included 12 clinical reports. Pooled retinal sensitivity improvement was 73.8% (95% confidence interval, 56.0%-86.1%; 25/33 participants), and pooled visual function improvement was 52.3% (95% confidence interval, 38.0%-66.2%; 28/52 participants). The pooled adverse-event proportion was 42.6% (95% confidence interval, 27.2%-59.5%; 42/90 participants), intraocular inflammation was 45.5% (95% confidence interval, 34.6%-56.8%; 36/81 participants), and intraocular-pressure elevation was 34.9% (95% confidence interval, 24.2%-47.4%; 22/63 participants). Product-specific dose analyses showed greater inflammatory or ocular serious adverse-event frequencies at higher vector exposure. AAV-RPGR gene therapy demonstrates clinically relevant functional signals across multiple outcome domains with a structured and monitorable ocular safety profile. Cohort-linked synthesis, dose-specific interpretation, standardized outcome definitions, and long-term multinational follow-up provide a rigorous framework for subsequent clinical development.