Advanced therapeutic approaches for inherited retinal diseases: an umbrella review

OBJECTIVES: To evaluate the efficacy and safety of advanced therapeutic approaches for inherited retinal disease (IRD) using evidence from systematic reviews and meta-analyses. DESIGN: Umbrella review. DATA SOURCES: We searched for Epistemonikos, PubMed, Scopus, PsycInfo, Google Scholar, Joanna Briggs Institute Evidence Synthesis, the Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects from inception to November 2024. ELIGIBILITY CRITERIA: This included English-language systematic review and meta-analysis assessing advanced therapies in patients with IRD (including congenital retinal dystrophies, retinal dystrophies, retinitis pigmentosa (RP), Stargardt disease, X linked RP, achromatopsia, cone-rod dystrophy, choroideraemia and X linked retinoschisis). Reviews that did not meet the methodological quality threshold were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened and extracted the data, with disagreements resolved by consensus. Findings were synthesised narratively due to the substantial overlap of primary studies. RESULT: Six systematic reviews and meta-analyses published from 2020 onwards were included, comprising between 6 and 21 primary studies per review. The therapies evaluated included gene therapy, cell-based therapy and stem cell-based interventions. Reported effect estimates showed modest to clinically meaningful improvements in best-corrected visual acuity and retinal structural outcomes in selected IRD subtypes, although effect sizes varied widely across interventions and conditions. The GRADE certainty of evidence ranged from moderate to low, reflecting bias, imprecision and heterogeneity risks. Substantial overlap of primary studies was observed (corrected covered area = 28.9%), precluding quantitative pooling across reviews. CONCLUSION: The findings suggest notable improvements in visual acuity, retinal structure and other critical outcomes, with therapies such as cell therapy, gene therapy and stem cell therapy showing promising results in enhancing treatment efficacy. Although there are examples of successes with supportive evidence, the overall evidence is not sufficiently strong to make general recommendations, as studies still need to be evaluated on a case-by-case basis. Further high-quality, large-scale randomised controlled trials are needed to better confirm their efficacy and safety.