Gene therapy in patients with choroideremia: a meta-analysis of clinical trials

To systematically review the published literature on clinical trials of gene therapy in patients with choroideremia (CHM gene mutation).

A comprehensive search was conducted in Medline, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov up to April 2026, and was limited to studies published in English or Spanish. Clinical trials evaluating the efficacy of gene therapy in patients with a confirmed molecular diagnosis were included. Methodological quality was assessed using the Revised Cochrane Risk-of-Bias Tool for Randomised Trials and ROBINS-I. A random-effects meta-analysis was performed to compare best-corrected visual acuity (BCVA) in treated versus untreated eyes by standardised mean differences (SMD). Heterogeneity was assessed using the I² statistic and the Q test.

Eight intervention arms from seven clinical trials (377 eyes) assessed the effects of gene therapy on BCVA, showing a small, non-significant improvement (SMD 0.34; 95% CI: -0.52 to 1.19; p = 0.38) with high heterogeneity (I²=89.6%, p < 0.01). Exploratory subgroup analyses by dose suggested differences across dose groups, but these findings should be interpreted cautiously because of the limited number of studies and high heterogeneity. Seven clinical trials (351 eyes) found no significant effect on retinal sensitivity, though lower doses showed more consistent positive trends. Three trials (276 eyes) reported no significant change in foveal thickness overall, with high variability and dose-related differences. No publication bias was detected (Egger's test: p = 0.54).

Some individual studies showed significant visual improvements with gene therapy in choroideremia, but the overall pooled effect was modest and not conclusive. High heterogeneity reflects varied study designs and criteria. More rigorous, standardized trials are needed to confirm gene therapy's efficacy.