Acute Angle-Closure Glaucoma And Non-Ophthalmic Anticholinergics: A Sex-Stratified Pharmacovigilance Disproportionality Analysis

Acute angle-closure glaucoma (ACG) is a vision-threatening emergency that may be precipitated perioperatively in anatomically susceptible patients, for example during pupillary dilation with anticholinergic agents such as Tropicamide. ACG onset can compromise surgical outcomes and increase the risk of irreversible vision loss. Although anticholinergics are widely prescribed across multiple specialties, the association between non-ophthalmic anticholinergic exposure and ACG remains incompletely characterized. This study evaluates the association between non-ophthalmic anticholinergics and ACG—including sex-stratified effects—to inform surgical risk stratification, preoperative medication review, and perioperative management.

Disproportionality analyses were performed using a large international pharmacovigilance database maintained by the U.S. Food and Drug Administration (FDA).

Only non-ophthalmic medications with a primary, exclusive antimuscarinic mechanism were included; agents with mixed or secondary anticholinergic activity were excluded. Reports of ACG associated with anticholinergics in the FDA Adverse Event Reporting System (FAERS) from January 2004 to February 2026 were analyzed. OpenVigil 2.1 was used to generate reporting odds ratios (ROR), proportional reporting ratios (PRR), and chi-squared (χ²) with Yates’ correction. Sex-stratified analyses were subsequently performed. Signals were considered significant if they met established pharmacovigilance thresholds of ROR 95% CI > 1, PRR ≥ 2.0, χ² ≥ 4.0, and case count ≥ 3. This indicates disproportionate ACG reporting relative to other FDA-approved drugs.

Nine non-ophthalmic anticholinergics demonstrated significant ACG signals. By indication: overactive bladder — fesoterodine ROR 6.61 (95% CI 2.97–14.74), solifenacin 6.52 (3.85–11.03), tolterodine 5.17 (2.46–10.86); movement disorders — biperiden 8.36 (3.13–22.30); gastrointestinal disorders — scopolamine 6.72 (2.52–17.93); respiratory disease — glycopyrrolate 12.83 (7.43–22.15), ipratropium 4.06 (2.44–6.75), tiotropium 2.88 (2.00–4.16), umeclidinium 2.36 (1.34–4.17). In sex-stratified analyses, five anticholinergics demonstrated significant ACG signals exclusively in females: scopolamine 9.62 (3.60–25.69), tolterodine 4.96 (2.22–11.07), ipratropium 4.69 (2.66–8.29), fesoterodine 4.39 (1.41–13.65), and tiotropium 3.14 (2.06–4.79).

Non-ophthalmic anticholinergic use represents a clinically relevant and potentially modifiable risk factor for ACG in anatomically susceptible patients. Multiple commonly prescribed agents had disproportionate ACG reporting, with several signals observed exclusively in females. This sex-specific pattern aligns with known female-predominant anatomic susceptibility to ACG and reinforces biological plausibility. 

These findings underscore the critical role of systematic preoperative medication reconciliation before pharmacologic dilation. Early identification of at-risk patients—particularly females on anticholinergic therapy—facilitates tailored perioperative management and may reduce preventable angle-closure events during cataract surgery.