Abstract
PURPOSE: This study aimed to conduct a systematic review and meta-analysis to synthesize clinical evidence on adeno-associated viral (AAV)-based RPGR gene therapy for X-linked retinitis pigmentosa (XLRP), guiding clinical decisions and future research. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Prospective Register of Systematic Reviews (PROSPERO; CRD420251008337) registration, we searched PubMed, Embase, and other databases through March 2025, including controlled clinical trials evaluating AAV gene therapy for RPGR-related XLRP. Two reviewers independently screened literature, extracted data, and assessed bias using the Cochrane tool. Meta-analyses were performed in RevMan version 5.4, calculating risk ratios (RRs) for dichotomous outcomes and mean difference /standardized mean difference (MD / SMD) for continuous outcomes, with random/fixed-effects models based on heterogeneity (I² > 50%). RESULTS: Five articles from three studies (205 patients) were included. Gene therapy significantly improved low-luminance visual acuity (LLVA) ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 6 months (RR = 3.79, P = 0.03) and retinal sensitivity at 6 months (MD = 1.06, P = 0.001) and 12 months (MD = 2.47, P < 0.00001), but not best-corrected visual acuity (VA) or LLVA ≥15 letters. Ocular treatment-emergent adverse event (TEAE) risk increased significantly (RR = 5.52, P < 0.00001), with common events including anterior chamber inflammation and intraocular inflammation. A trend toward higher serious adverse events (SAEs) was observed (odds ratio [OR] = 3.36, P = 0.05). CONCLUSIONS: Gene therapy demonstrates short-term efficacy for XLRP, with 6 months as a critical evaluation time point, but requires vigilance for ocular TEAE risks. Heterogeneity and small sample sizes highlight the need for large-scale, long-term multicenter trials to optimize protocols and advance safe clinical application. TRANSLATIONAL RELEVANCE: XLRP, a severe hereditary retinal dystrophy primarily caused by RPGR gene mutations, lacks curative treatments. AAV-mediated RPGR gene therapy shows promise in early trials, but systemic evaluation of its efficacy and safety is absent. This evaluates gene therapy as a novel approach, noting short-term efficacy but ocular AE risks.