Pilocarpine, Topiramate, and Other Medications Significantly Increase Acute Angle-Closure Crisis Risk, While Pharmacologic Dilation Remains Safe
Background
Acute Angle-Closure Crisis (AACC) is an ophthalmic emergency that can lead to rapid vision loss, often associated with anatomical predispositions or medication side effects. Understanding the true epidemiology of AACC, the safety profile of routine ophthalmic procedures like pharmacologic dilation, and identifying specific medication-associated risks are crucial for patient safety and clinical decision-making. Current knowledge on population-level AACC incidence and specific drug-induced risks, particularly within a large US cohort, has been limited, leading to potential gaps in risk assessment and preventative strategies for this sight-threatening condition.
Study Design
This retrospective clinical cohort study analyzed deidentified electronic medical record data from adults (≥18 years) across a multicenter federated electronic health record network from 2010 to 2025. AACC cases were identified using ICD-10-CM codes followed by definitive therapeutic intervention within 14 days. The incidence, prevalence, and diagnostic trends were evaluated using Mann-Kendall tests. Dilation-associated AACC risk was assessed among 3,400,372 dilation-associated ophthalmic examinations, with incident AACC identified within 14 days (with a 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.
Results
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%. Both AACC incidence and PACG prevalence among AACC patients increased over time (all P < 0.001). Gonioscopy utilization declined, while anterior segment imaging increased (all P < 0.001). Across 3,400,372 dilation-associated examinations among 2,444,570 patients, post-dilation AACC was rare: > 3.1 per 100,000 (95% CI: 2.3-3.4), with similar findings in a 24-hour sensitivity analysis. These events concentrated among patients with anatomical risk factors. Increased AACC risk was observed for medications with established associations: pilocarpine (HR: 1.77), topiramate (2.07), hydrochlorothiazide (2.13), albuterol (1.57), enoxaparin (2.17), and trihexyphenidyl (2.12) (all P < 0.05).
Key Findings
- Cumulative AACC incidence was 0.014% from 2010-2025, with PACG prevalence among AACC patients at 16.7%.
- Post-dilation AACC was rare, occurring at 3.1 per 100,000 examinations (95% CI: 2.3-3.4).
- AACC incidence and PACG prevalence among AACC patients both increased over time (all P < 0.001).
- Medications like pilocarpine (HR: 1.77), topiramate (2.07), and hydrochlorothiazide (2.13) significantly increased AACC risk.
- Other drugs, including albuterol (HR: 1.57), enoxaparin (2.17), and trihexyphenidyl (2.12), also showed increased AACC risk (all P < 0.05).
Why It Matters
This study provides critical, large-scale epidemiological data on AACC in the US, affirming the overall safety of pharmacologic dilation while highlighting specific medication risks. Clinicians should exercise heightened vigilance when prescribing pilocarpine, topiramate, hydrochlorothiazide, albuterol, enoxaparin, and trihexyphenidyl, especially in patients with known anatomical risk factors for AACC. This data refines risk assessment for routine ophthalmic procedures and medication management, potentially leading to improved patient screening and preventative strategies. The observed increase in AACC incidence and PACG prevalence, coupled with declining gonioscopy, suggests a need for updated diagnostic protocols and clinician education to ensure timely identification and management of at-risk individuals.
acute-angle-closure-crisis
aacc
ophthalmology
medication-safety
epidemiology
pilocarpine