Oral acetylcysteine and the risk of age-related macular degeneration

Tsai HR, Chang WC, Lee YC. Oral acetylcysteine and the risk of age-related macular degeneration. Ophthalmology. 2026;133(2):223-232.

This retrospective cohort study from Taiwan investigated whether oral N-acetylcysteine (NAC) – an antioxidant and glutathione precursor – is associated with a reduced risk of age-related macular degeneration (AMD). Using data from Taiwan’s National Health Insurance Research Database, researchers identified over 160,000 patients older than 50, ultimately matching 5,234 NAC users with 5,234 non-users via propensity score matching to control for baseline differences in demographics and comorbidities.

The results were striking: NAC users had an 81% lower risk of developing AMD overall (HR 0.19), with significant reductions seen for both dry AMD (HR 0.19) and wet AMD (HR 0.31). The protective effect held up across subgroups stratified by age, sex, and various comorbidities. A dose-response relationship was also observed, with higher cumulative doses of NAC correlating with greater risk reduction, particularly for dry AMD – though significant dry AMD protection only emerged at the higher dosage thresholds (180+ cumulative defined daily doses).

The authors propose two main biological mechanisms to explain these findings. First, NAC bolsters the glutathione antioxidant system in retinal pigment epithelial cells, helping neutralize the reactive oxygen species implicated in AMD progression. Second, NAC may suppress inflammatory pathways, including NF-κB signaling and pro-inflammatory cytokines like interleukin-6, that drive the chronic retinal degeneration characteristic of AMD.

The study’s key strengths include its large, population-level sample and extended follow-up period. However, notable limitations include the lack of data on smoking status and BMI (both AMD risk factors), reliance on insurance codes rather than clinical evaluations for AMD diagnosis, and the retrospective observational design, which cannot establish causation. The authors conclude that the findings warrant further investigation through prospective clinical trials to confirm NAC’s potential as a preventive treatment for AMD.