Association of Anticholinergic Drug Use With Risk for Late Age-Related Macular Degeneration.

Importance: Amyloid-β is a major component of retinal drusen, the primary lesions of age-related macular degeneration (AMD), and autopsy and animal models suggested that anticholinergic drug (ACD) use increased brain amyloid-β deposition.

Objective: To investigate the association between exposure to ACDs and late AMD (features of neovascular AMD or geographic atrophy of the retinal pigment epithelium in at least 1 eye).

Design, Setting and Participants: A multicenter case-control study in 4 French ophthalmologic centers comprising 200 cases with late AMD and 200 controls enrolled from July 2016 to June 2017.

Exposures: Exposure to at least 3 months of ACDs started before AMD diagnosis was recorded during a specific interview. A dose-effect association with cumulative exposure duration and Anticholinergic Burden Score was explored. The association between ACD exposure and AMD was assessed by multivariate logistic regression analysis adjusted for age, sex, smoking status, family history of AMD, alcohol consumption, and use of anticoagulant and anti-inflammatory drugs. Odds ratios (ORs) and 95% confidence intervals were estimated.

Main Outcomes and Measures: Association between exposure to ACDs and late AMD.

Results: Among case participants, the mean (SD) age was 74.8 (9.2) years, 129 (64.5%) were women, 192 (96%) were white, 65 (32.5%) had geographic atrophy, 135 (67.5%) had neovascular AMD, 116 (58%) had unilateral AMD, and 84 (42%) had bilateral AMD. Among control participants, the mean (SD) age was 75.5 (7.2) years, with 116 (58%) women and 187 (93.5%) white participants. Twenty-six cases (13%) and 10 controls (5%) were exposed to ACDs throughout life for at least 3 months before AMD onset. Risk of AMD was increased with ever exposure to ACDs (adjusted OR [aOR], 2.84; 95% CI, 1.33-6.06; P = .007), high Anticholinergic Burden Score (≥3) (aOR, 6.42; 95% CI, 1.38-29.92; P = .02), and longest cumulative exposure to ACD (≥15 years) (aOR, 5.88; 95% CI, 1.22-28.31; P = .03).

Conclusions and Relevance: Risk of late AMD may be increased with at least 3 months' use of ACDs. A dose-effect association was suggested by a greater association with prolonged use and high Anticholinergic Burden Score. Further studies, in particular those with longitudinal design, are needed to confirm this association.