Association between Regular Hypnotic Use and Age-Related Macular Degeneration

Previous studies have confirmed the presence of benzodiazepine receptors in the retina, and exploratory research has suggested that the use of hypnotics may be linked to changes in retinal function and an increased risk of maculopathy. This indicates that regular use of hypnotic medications is likely associated with age-related macular degeneration (AMD). However, the precise relationship remains largely unclear. In this study, we aimed to investigate this association in the UK Biobank. Regular use of hypnotics, including benzodiazepines or Z-meds (non-benzodiazepine hypnotics such as zolpidem and zaleplon) were assessed at baseline. Nearest-neighbor propensity score matchings (PSM) were implemented to control for potential confounding variables. Cox proportional hazards regression with robust variance estimation was utilized to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for demographic, socioeconomic, systemic, and lifestyle variables. Sensitivity analyses were performed using traditional Cox proportional hazards regression on the original cohort, with additional subgroup analyses stratified by age group and sex. Following the PSM procedure, 1,899 benzodiazepine users and 7,557 non-users were selected from the benzodiazepines cohort, and 321 Z-meds users and 1,284 non-users were selected from the Z-meds cohort. A total of 262 participants in the benzodiazepines cohort developed incident AMD during follow-up after PSM, compared with 49 participants in the Z-meds cohort. Upon adjusting for covariates, the prolonged use of Z-meds was associated with an elevated AMD risk (HR, 2.15; 95% CI, 1.23-3.74; P = 0.007), whereas no significant association was observed for the regular use of benzodiazepines (HR, 0.97; 95% CI, 0.73-1.30; P = 0.854). Sensitivity analyses demonstrated consistent associations. Subgroup analyses also indicated consistent associations across various categories. Prolonged use of Z-meds may elevate the risk of developing AMD. Given the increasing prescription of Z-meds for the treatment of insomnia, these findings underscore the necessity of considering potential ocular risks and requiring more frequent monitoring.