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207 - Anticholinergic drugs use and risk for age-related macular degeneration: a case–control study

Amyloid-beta is a major component of retinal drusen, the primary lesions of age-related macular degeneration, and autopsy and animal models suggested that anticholinergic drug use increased brain β-amyloid deposition. The aim was to investigate the relation between exposure to anticholinergic drugs (ACDs) and late age-related macular degeneration (AMD).

A multicenter case–control study in 4 French ophthalmologic centers. 200 cases with late AMD and 200 controls were enrolled from July 2016 to June 2017. Exposure to at least 3 months of ACDs started before AMD diagnosis was recorded during a specific interview. A dose–effect relation 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, gender, smoking status, family history of AMD, alcohol consumption, and use of anticoagulant and anti-inflammatory drugs. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. The main outcome was the association between exposure to ACDs and late AMD.

13% of cases and 5% of controls were exposed to ACDs throughout lifefor 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=0.007), high Anticholinergic Burden Score (≥ 3) (aOR=6.42, 95% CI 1.38-29.92, p=0.02), and longest cumulative exposure to ACD (≥ 15 years) (aOR=5.88, 95% CI 1.22-28.31, p=0.03).

ACD use is suspected to increase brain β-amyloid deposition. Several studies founded amyloid-beta in drusen of eyes with AMD, wich is suspected, as in Alzheimer disease, to promote oxidative stress and local inflammation, contributing to retinal degenerative events. As well, exposure of retinal pigment epithelium to UV radiation may be increased via mydriasis induced by ACDs. 

The data concerning covariates and exposure to ACDs were self-reported, which suggests potential recall bias in this study and possible underestimation of ACD use. However, these data were assessed similarly in cases and controls. Cases were representative of the AMD population, with similar diagnostic age and proportion of geographic atrophy and neovascular AMD and the same exposure to the main other risk factors. Concerning other covariates such as medical indications associated with ACD use, controls were similar to cases. Moreover, ACD use was the only medication recorded in this study associated with increased risk of AMD. Therefore, a selection bias of controls is unlikely. The case–control design of this study did not allow for assessing a causative relation.

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