Association Between Melatonin Use and Cataract Risk: A Target Trial Emulation Retrospective Cohort Study

Oxidative stress has been shown to play an important role in the development of cataracts. Melatonin is an endogenous hormone that has been proposed to have a protective effect against oxidative stress; however, its association with the risk of cataracts is uncertain. This target trial emulation study aimed to investigate the relationship between the use of melatonin and the risk of cataracts using TriNetX electronic health records from 2015 to 2023. Adults aged 40 years or older who were diagnosed with a sleep disorder and initiated treatment with either melatonin or a hypnotic benzodiazepine (BZD) were included. Patients receiving hypnotic BZD therapy constituted the active comparator group. Propensity score matching (PSM) was performed to control for covariance. Exposure was defined as the initiation of melatonin or hypnotic BZD therapy. The primary outcomes were the incidence of age-related cataracts and other cataract types, assessed using Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to reduce potential bias. After PSM, 5507 participants were included in each group. Compared with hypnotic BZD users, melatonin users were associated with a significantly lower risk of age-related cataracts (HR, 0.741; 95% CI, 0.681-0.807) and other cataracts (HR, 0.503; 95% CI, 0.433-0.584). These associations remained consistent across all subgroups and sensitivity analyses. In this target trial emulation cohort study, the use of melatonin was associated with a reduced risk of cataracts, suggesting a potential protective effect that warrants further investigation.