The safety and efficacy of gene therapy treatment for monogenic retinal and optic nerve diseases: A systematic review

Genet Med. 2022 Mar;24(3):521-534. doi: 10.1016/j.gim.2021.10.013. Epub 2021 Nov 30.


Purpose: This study aimed to systematically review and summarize gene therapy treatment for monogenic retinal and optic nerve diseases.

Methods: This review was prospectively registered (CRD42021229812). A comprehensive literature search was performed in Ovid MEDLINE, Ovid Embase, Cochrane Central, and clinical trial registries (February 2021). Clinical studies describing DNA-based gene therapy treatments for monogenic posterior ocular diseases were eligible for inclusion. Risk of bias evaluation was performed. Data synthesis was undertaken applying Synthesis Without Meta-analysis guidelines.

Results: This study identified 47 full-text publications, 50 conference abstracts, and 54 clinical trial registry entries describing DNA-based ocular gene therapy treatments for 16 different genetic variants. Study summaries and visual representations of safety and efficacy outcomes are presented for 20 unique full-text publications in RPE65-mediated retinal dystrophies, choroideremia, Leber hereditary optic neuropathy, rod-cone dystrophy, achromatopsia, and X-linked retinoschisis. The most common adverse events were related to lid/ocular surface/cornea abnormalities in subretinal gene therapy trials and anterior uveitis in intravitreal gene therapy trials.

Conclusion: There is a high degree of variability in ocular monogenic gene therapy trials with respect to study design, statistical methodology, and reporting of safety and efficacy outcomes. This review improves the accessibility and transparency in interpreting gene therapy trials to date.

Keywords: Gene therapy; Inherited retinal disease; Luxturna; Retinal dystrophy; Systematic review.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Color Vision Defects* / therapy
  • Genetic Therapy / methods
  • Humans
  • Optic Nerve Diseases* / genetics
  • Optic Nerve Diseases* / therapy
  • Retina
  • Retinal Dystrophies*