"Current evidence supports a treatment-burden–reducing adjunctive role for gene therapy rather than replacement of anti-VEGF therapy."
A systematic review and meta-analysis published in the American Journal of Ophthalmology (in press, April 4, 2026) has evaluated the current state of gene therapy for neovascular age-related macular degeneration (nAMD). The analysis examined eight prospective clinical trials involving 203 participants.
Key Findings
Visual Acuity
No statistically significant improvement in best-corrected visual acuity (BCVA) was observed. The mean difference was just 0.54 letters, with confidence intervals crossing zero.
Anatomical Outcomes
Central subfield thickness (CST) showed a statistically significant reduction of 37.13 µm. This indicates better control of retinal fluid and disease activity.
Rescue Injections
Approximately 44% of treated eyes required rescue anti-VEGF injections after receiving gene therapy.
Safety
- Inflammation occurred in about 20% of cases
- Retinal hemorrhage in about 12%
- Serious adverse events ranged from 21% to 38%
- Mortality was reported at around 8%, though the authors noted this may not be treatment-related given the older patient demographics
Publication Bias
Bias was identified for some efficacy outcomes, particularly BCVA and CST.
Author Conclusions
The authors state that current evidence supports a treatment-burden–reducing adjunctive role for gene therapy rather than replacement of anti-VEGF therapy.
Limitations
Evidence is limited by:
- Small sample sizes
- Early-phase trial designs
- Heterogeneity in gene delivery methods, vectors, and outcome measures
Of note, several phase three studies are currently underway.