Efficacy and safety of AAV-mediated gene therapy for CNGA3- and CNGB3-associated achromatopsia, pooling 9 human studies identified via systematic search from inception to March 2026.
Gene therapy produced a statistically significant but modest improvement in BCVA (mean difference: +2.65 ETDRS letters) and contrast sensitivity; color discrimination showed small but significant gains; retinal sensitivity did not improve significantly. Adverse events occurred in ~29% of cases but were generally mild and transient. Dose-stratified analysis suggested a non-linear response favoring lower-to-intermediate doses. Evidence of benefit was primarily in CNGA3-associated disease; efficacy in CNGB3-associated achromatopsia remains uncertain.
- Evidence base is small (9 studies), limiting statistical power and generalizability. - Genotype-specific conclusions are asymmetric — CNGB3 outcomes are insufficiently characterized. - Follow-up reflects short- to mid-term data only; long-term durability is unknown.
AAV gene therapy for achromatopsia appears safe short-term and may offer modest visual benefit, particularly for CNGA3 patients — but the gains are small and CNGB3 evidence is weak. Clinicians should counsel patients on realistic expectations and the need for longer-term follow-up data before broader adoption.
