Systemic Medication Associations with Presumed Advanced or Uncontrolled Primary Open-Angle Glaucoma

Abstract

Purpose: To identify associations between systemic medications and primary open-angle glaucoma (POAG) requiring a procedure using United States insurance claims data in a hypothesis-generating study. Design: Database study. Participants: In total, 6130 POAG cases (defined as patients with POAG undergoing a glaucoma procedure) were matched to 30 650 controls (defined as patients undergoing cataract surgery but without a coded glaucoma diagnosis, procedure, or medication) by age, gender, and region of residence. Methods: Participant prescription drug use was calculated for the 5-year period before the glaucoma procedure or cataract surgery. Separately for individual generic drugs and drug classes, logistic regression was used to assess the association with POAG status. This was done across all generic drugs and drug classes that were prescribed in at least 1% of cases and controls. Analyses were adjusted for age, sex, region of residence, employment status, insurance plan type, and the total number of drugs prescribed. Main Outcome Measures: Odds ratio (OR) and 95% confidence intervals (CIs) for the association between each drug or drug class and POAG. Results: The median age of participants was 72 years, and 52% were women. We tested for associations of POAG with 423 drug classes and 1763 generic drugs, resulting in a total of 2186 statistical tests and a Bonferroni-adjusted significance threshold of P < 2.3 × 10−5. Selective serotonin reuptake inhibitors (SSRIs) were strongly associated with a reduced risk of POAG (OR, 0.70; 95% CI, 0.64–0.76; P = 1.0 × 10−15); the most significant drug in this class was citalopram (OR, 0.66; 95% CI, 0.57–0.77; P = 1.2 × 10−7). Calcium channel blockers were strongly associated with an increased risk of POAG (OR, 1.26; 95% CI, 1.18–1.35; P = 1.8 × 10−11); the most significant drug in this class was amlodipine (OR, 1.27; 95% CI, 1.18–1.37; P = 5.9 × 10−10). Conclusions: We present data documenting potential associations of SSRIs and calcium channel blockers with POAG requiring a procedure. Further research may be indicated to better evaluate any associates of serotonin metabolism or calcium channels in glaucoma, or establish whether the associations are due to variations in the patterns for prescribing these drugs.