The efficacy and safety of adeno-associated virus-mediated gene therapy for CNGA3- and CNGB3-associated achromatopsia: A genotype-aware systematic review and meta-analysis.

We evaluated the efficacy and safety of adeno-associated virus-mediated gene therapy for CNGA3 (Cyclic Nucleotide-Gated Channel Alpha 3)- and CNGB3 (Cyclic Nucleotide-Gated Channel Beta 3)-associated achromatopsia. Human studies were systematically searched from database inception to March, 2026, and 9 studies were included. Pooled analysis showed modest, but statistically significant, improvement in best-corrected visual acuity, with a mean difference of 2.65 letters, and significant improvement in contrast sensitivity. Retinal sensitivity did not improve significantly, whereas color discrimination showed small but significant improvement. Dose-stratified findings showed numerically greater benefit at lower to intermediate doses than at the highest dose, with these comparisons interpreted descriptively. Safety analysis indicated an approximate adverse-event probability of 29%, with events generally mild, transient, and manageable. Current evidence suggests favorable short- to mid-term safety and modest functional benefit, mainly in CNGA3-associated achromatopsia, while efficacy in CNGB3-associated disease remains uncertain.