Oral acetylcysteine and the risk of age-related macular degeneration: A retrospective cohort study.

Purpose: N-acetylcysteine (NAC) functions as both a direct antioxidant agent and precursor for glutathione synthesis, both of which are implicated in the pathogenesis of age-related macular degeneration (AMD). However, whether NAC use confers protective effects against AMD remains unclear. This study aimed to investigate potential associations between NAC use and the risks of AMD development in a large cohort of the Taiwanese population.

Design: Retrospective cohort study PARTICIPANTS AND CONTROLS: The study included 22,498 NAC users and 138,607 non-NAC users between 2003 and 2017 before propensity score matching (PSM).

Methods: This nationwide, population-based study leveraged data from the Taiwan National Health Insurance Research Database. PSM was applied to ensure comparability of baseline demographics and comorbidities between NAC users and non-users. Stratified analyses by age and sex were conducted, and a cumulative defined daily dose was calculated to evaluate dose-response relationships among NAC users. Cox proportional hazards regression models were employed post-PSM to estimate the hazard ratio (HR) for each outcome.

Main outcome measures: Outcome measures included the HR of overall, dry, and wet AMDs RESULTS: After PSM, 5234 patients were included in each cohort: NAC users and non-NAC users. NAC users exhibited a significantly lower risk of AMD than non-users did (HR 0.19; 95% CI: 0.14-0.26; p < 0.001). This protective effect was observed for both dry (HR 0.19; 95% CI: 0.14-0.26) and wet (HR 0.31; 95% CI: 0.12-0.81) AMDs. Stratified analyses demonstrated a reduced risk of AMD among NAC users, consistent across different age and sex groups. A dose-response relationship was identified, with higher cumulative doses of NAC associated with greater reductions in the risk of AMD and dry AMD. Sensitivity analyses for patients aged ≥ 60 and ≥ 70 years further supported the association between NAC use and reduced AMD risk, particularly for dry AMD.

Conclusions: NAC use was associated with a significantly reduced risk of AMD, especially dry AMD. These findings support the need for further investigation into the effectiveness of NAC as a preventive treatment for AMD.