Epidemiology, Safety of Dilation, and Medication-Associated Risk of Acute Angle-Closure Crisis in the United States

To evaluate the epidemiology of acute angle-closure crisis (AACC), the safety of pharmacologic dilation, and medication-associated AACC risk in the United States.

Retrospective clinical cohort study.

Adults (≥18 years) in a multicenter federated electronic health record network.

Using deidentified electronic medical record data from 2010 to 2025, AACC cases were identified using ICD-10-CM codes followed by definitive therapeutic intervention within 14 days. Incidence, prevalence, and diagnostic trends were evaluated with Mann-Kendall tests. Dilation-associated AACC risk was assessed among patients undergoing dilation-associated ophthalmic examinations, with incident AACC identified within 14 days (with 24-hour sensitivity analysis). Medication-associated AACC risk was evaluated using active-comparator cohorts with 1:1 propensity score matching and Cox proportional hazards models over a 30-day window.

AACC incidence (per 100,000 dilation-associated examinations) and hazard ratios (HRs) with 95% confidence intervals (CIs) for medication-associated AACC risk.

From 2010 to 2025, the cumulative incidence of AACC was 0.014%, and the prevalence of primary angle-closure glaucoma (PACG) among patients with AACC was 16.7%. AACC incidence and the prevalence of PACG among patients with AACC increased over time (all P < .001). Gonioscopy utilization declined, whereas anterior segment imaging increased (all P < .001). Across 3,400,372 dilation-associated examinations among 2,444,570 patients, post-dilation AACC was rare (3.1 per 100,000; 95% CI: 2.3-3.7), with similar findings in a 24-hour sensitivity analysis; events concentrated among patients with anatomical risk factors. Increased AACC risk was observed for medications with established associations and some with less established associations, including lactulose (HR: 1.67), metoclopramide (1.38), sumatriptan (1.64), prazosin (1.32), and terazosin (1.77) (all P < .05). Previously unreported associations were observed for calcitonin gene-related peptide (CGRP) monoclonal antibodies (erenumab [1.33]), calcium channel blockers (CCBs) (verapamil [1.89], diltiazem [1.74]), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab [1.54], evolocumab [1.46]) (all P < .05).

AACC following pharmacologic dilation was rare and occurred predominantly among anatomically predisposed patients, supporting the safety of dilation in routine care. Medication-associated risk signals highlight the importance of proactive ocular risk assessment and medication reconciliation. Novel associations with CCBs, CGRP monoclonal antibodies, and PCSK9 inhibitors warrant further investigation.