Gene therapy for neovascular age-related macular degeneration (nAMD) may help reduce the need for frequent anti-VEGF injections, although evidence for meaningful visual acuity gains remains limited, a new review suggests.
But findings did suggest that gene therapy may help control retinal anatomy and disease activity even if corresponding visual improvements were not yet consistently demonstrated.
The systematic review and meta-analysis were reported in a review article in press on 4 April 2026 for the American Journal of Ophthalmology.
The authors said that, for ophthalmologists and optometrists, the findings reinforced that gene therapy remained an emerging adjunctive strategy rather than a replacement for established anti-VEGF management.
The review analysed eight prospective clinical trials involving 203 treated participants with nAMD. Most investigated adeno-associated virus (AAV)-based gene therapies designed to deliver anti-VEGF constructs directly into the eye.
Researchers concluded that while gene therapy demonstrated encouraging anatomical outcomes and an acceptable safety profile, it had not yet consistently improved functional vision outcomes compared with existing standards of care.
nAMD remains one of the leading causes of irreversible vision loss among older adults worldwide. Although intravitreal anti-VEGF injections have transformed management of the disease, the need for ongoing, often lifelong injections creates a substantial burden for patients, carers and clinics.
The authors said gene therapy could potentially address this challenge by enabling sustained production of therapeutic proteins following a single procedure or infrequent dosing schedule.
“Current evidence supports a treatment-burden–reducing adjunctive role rather than replacement of anti-VEGF therapy,” the authors wrote.
Eligible studies included prospective interventional trials ranging from early phase dose-escalation studies to randomised clinical trials.
Encouraging anatomical outcomes
Primary outcomes assessed included best-corrected visual acuity (BCVA), central subfield thickness (CST), need for rescue anti-VEGF injections, mortality and adverse events.
Across the pooled analysis, researchers found no statistically significant improvement in BCVA. The mean difference was 0.54 letters, with confidence intervals crossing zero, indicating inconsistent functional benefit across studies.
However, anatomical outcomes appeared more encouraging. Central subfield thickness, a key marker of retinal fluid and disease activity, showed a statistically significant reduction of 37.13 µm.
The findings suggested gene therapy may help control retinal anatomy and disease activity even if corresponding visual improvements were not yet consistently demonstrated.
Serious adverse events
Importantly for retinal specialists, the review found that about 44% of treated eyes still required rescue anti-VEGF injections after gene therapy. This indicated that current approaches were unlikely to eliminate injections altogether in the near term.
Safety outcomes were described as generally acceptable, with low-to-moderate rates of adverse events reported across studies. Inflammation occurred in about 20% of cases, while retinal haemorrhage was reported in about 12%.
Serious adverse events ranged between 21% and 38%, although the authors noted variability in reporting definitions and patient populations between studies. Mortality rates were reported at around 8%, although researchers said these were not necessarily treatment-related given the older patient demographics typically affected by nAMD.
The researchers identified publication bias for some efficacy outcomes, particularly BCVA and CST, highlighting the need for caution when interpreting results.
They said the evidence base remained limited by small sample sizes, early-phase trial designs and heterogeneity in gene delivery methods, vectors and outcome measures.
Despite these limitations, the paper highlighted growing momentum in retinal gene therapy development. Several phase three studies were now underway and expected to provide clearer evidence regarding long-term efficacy, durability and safety, they said.
They said that if future trials demonstrated durable disease control with fewer injections, gene therapy could eventually reshape treatment pathways for nAMD and help reduce the logistical burden faced by patients and retina clinics.
