A new systematic review and meta-analysis published in the American Journal of Ophthalmology suggests gene therapy could reduce treatment burden for patients with neovascular age-related macular degeneration, but does not yet deliver consistent improvements in vision.
Published online in April 2026, the study analysed eight clinical trials involving 203 patients treated with gene therapy – primarily adeno-associated virus (AAV)–based anti-VEGF constructs – designed to provide sustained intraocular drug expression after a single or infrequent administration.
The findings highlight the growing interest in gene therapy as a potential alternative to standard anti-VEGF intravitreal injections, which remain effective but require frequent, long-term dosing.
Across the pooled data, gene therapy was associated with a significant reduction in central subfield thickness (CST), indicating a positive anatomical response. However, this did not translate into meaningful improvements in best-corrected visual acuity (BCVA), with results showing no statistically significant gain in vision. The authors note this disconnect between structural and functional outcomes remains a key challenge in translating early efficacy signals into real-world clinical benefit.
Importantly, the review found that around 44% of treated eyes still required supplementary anti-VEGF injections, reinforcing that gene therapy – at least in its current form – is unlikely to replace conventional treatment. Instead, it may serve as an adjunct therapy, helping to reduce injection frequency and ease the burden on both patients and clinics.
Safety outcomes were described as generally low-to-moderate risk, with inflammation reported in approximately 20% of cases and retinal haemorrhage in around 12%. Serious adverse events ranged from 21–38%, while mortality was reported at approximately 8%, though the authors caution that patient populations and study designs varied. Overall, the analysis found minimal variability across safety endpoints, suggesting a relatively consistent safety profile across studies.
The authors emphasise that current evidence is limited by small sample sizes, early-phase trial designs, and clinical heterogeneity. While the results point to encouraging anatomical and safety signals, they stop short of establishing gene therapy as a standalone treatment. Ongoing phase 3 trials are expected to play a critical role in determining whether gene therapy can deliver sustained visual outcomes and define its place in routine retinal care. For now, the technology appears best positioned as a treatment-burden–reducing strategy rather than a replacement for anti-VEGF therapy in nAMD.
Source: American Journal of Ophthalmology, Chen K-Y, Chan H-C, Chan C-M. Can Gene Therapy Revolutionize Treatment of Neovascular Age-Related Macular Degeneration? (Articles in Press, April 4, 2026).
