Systemic and ophthalmic drugs associated with glaucoma: an international, population-based observational study

Glaucoma is the leading cause of irreversible blindness worldwide. No postmarketing study has comprehensively assessed Food and Drug Administration (FDA)-approved drugs for glaucoma risk by subtype, therapeutic class, and sex. This study sought to identify systemic and ophthalmic drugs associated with glaucoma-related adverse events (AEs).

Population-based pharmacovigilance analysis of FDA Adverse Event Reporting System (FAERS) reports (January 2004-December 2024).

All glaucoma-related AEs, including normal-tension glaucoma (NTG), open-angle glaucoma (OAG), and angle-closure glaucoma (ACG).

Events were identified with the Medical Dictionary for Regulatory Activities Preferred Terms. Disproportionality was assessed using reporting odds ratios (RORs; 95% CI), Evans' criteria (n > 2; χ² > 4, Proportional reporting ratio > 2) and Bayesian confirmation (information component, lower 95% bound [IC₀₂₅] > 0). Analyses were stratified by subtype and sex.

Among 13,237,811 FAERS reports, 2 165 involved glaucoma-related events: 67 NTG, 372 OAG, and 1 726 ACG. Ranibizumab showed the strongest NTG signal (ROR = 83.73; 95% confidence interval [CI] = 38.20-183.66), especially in females (ROR = 162.36; 95% CI = 62.14-424.21). In OAG, significant signals were found for ranibizumab (ROR = 27.13; 95% CI = 15.60-47.19), topiramate (ROR = 21.58; 95% CI = 12.14-38.37), duloxetine (ROR = 9.09; 95% CI = 4.85-17.03), alendronate (ROR = 13.52; 95% CI = 8.78-20.82), and female-specific methylphenidate (ROR = 42.57; 95% CI = 20.94-86.51). In ACG, top signals included tropicamide (ROR = 166.10; 95% CI = 105.18-262.30), topiramate (ROR = 109.19; 95% CI = 98.54-121.00), imipramine (ROR = 33.96; 95% CI = 20.05-57.53), phentermine (ROR = 25.25; 95% CI = 16.73-38.13), and chlorpromazine (ROR = 13.93; 95% CI = 7.69-25.21). Tropicamide, topiramate, and imipramine showed stronger ACG signals in males. All associations were statistically significant (p < 0.0001; IC₀₂₅ > 0).

This large-scale FAERS analysis provides the most comprehensive assessment of drug-associated glaucoma risk to date. It confirms known associations and identifies novel signals across anti-vascular endothelial growth factor, cardiovascular, psychiatric, and respiratory drugs. Subtype- and sex-specific patterns underscore the need for individualized risk assessment, targeted postmarketing surveillance, and cautious prescribing to reduce preventable glaucoma-related vision loss.