Oral Acetylcysteine and the Risk of Age-Related Macular Degeneration: A Retrospective Cohort Study.

Abstract

N-acetylcysteine (NAC) functions as both a direct antioxidant agent and precursor for glutathione (GSH) 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. Retrospective cohort study. The study included 22 498 NAC users and 138 607 non-NAC users between 2003 and 2017 before propensity score matching (PSM). This nationwide, population-based study leveraged data from the Taiwan National Health Insurance Research Database. Propensity score matching was applied to ensure comparability of baseline demographics and comorbidities between NAC users and nonusers. 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 used post-PSM to estimate the hazard ratio (HR) for each outcome. Outcome measures included the HR of overall, dry, and wet AMD. After PSM, 5234 patients were included in each cohort: NAC users and non-NAC users. N-acetylcysteine users exhibited a significantly lower risk of AMD than nonusers did (HR, 0.19; 95% confidence interval [CI], 0.14-0.26; P < 0.001). This protective effect was observed for both dry AMD (HR, 0.19; 95% CI, 0.14-0.26) and wet AMD (HR, 0.31; 95% CI, 0.12-0.81). 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. Use of NAC 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. The author(s) have no proprietary or commercial interest in any materials discussed in this article.