And although clinicians have long recognized that dilation can occasionally trigger an acute angle-closure crisis (AACC) in susceptible eyes, just how often that happens in everyday practice, (particularly in the United States) has remained unclear.
With this in mind: A large new U.S. study sought to investigate the potential risk of such an occurrence.
Let's start at the beginning: Why would dilation raise a concern?
For most patients, dilation is perfectly safe. But in eyes with anatomically narrow angles, enlarging the pupil can push the iris into the eye's drainage angle, blocking the normal outflow of fluid.
If that happens, eye pressure can rise rapidly, resulting in an AACC—an ophthalmic emergency that requires immediate treatment.
And though previous studies—like the Rotterdam Study and the Zhongshan Angle-Closure Prevention (ZAP) Trial—have suggested that this complication is uncommon, large U.S. population data have been limited.
Got it. So, what did this study investigate?
Researchers conducted a large retrospective clinical cohort study to better understand AACC in the United States.
Specifically, they evaluated:
- frequency of AACC occurrence between 2010 and 2025.
- whether routine pharmacologic dilation increased short-term risk
- which patients were most likely to develop AACC after dilation
- whether commonly prescribed medications were associated with increased risk
They also examined changes in gonioscopy and anterior segment imaging over time.
And who was included in the analysis?
Using data from the TriNetX U.S. Collaborative Network, the researchers analyzed electronic health records (EHRs) from over 89 million adults.
The dilation safety analysis included:
- 2,444,570 patients
- 3,400,372 dilation-associated eye examinations
Patients with a previous AACC, primary angle-closure glaucoma (POAG), laser peripheral iridotomy or surgical iridectomy were excluded.
To note: A separate medication analysis evaluated 38 medication classes comprising 209 individual drugs using propensity score matching to balance baseline risk factors.
So what did they find?
Between 2010 and 2025, the cumulative incidence of AACC was just 0.014%.
Following routine pharmacologic dilation, only 105 patients developed AACC, corresponding to:
- 4.3 cases per 100,000 patients
- 3.1 cases per 100,000 dilation-associated examinations
When the researchers limited the analysis to attacks diagnosed within 24 hours of dilation, the incidence remained similarly low.
Any common characteristics of these patients?
Those who experienced AACC tended to be older and were much more likely to have known anatomical risk factors, including age-related cataract, narrow angles, glaucoma suspect status, and OAG.
Among the dilating drops studied, tropicamide, phenylephrine and cyclopentolate were not associated with increased AACC risk.
What else stood out?
Beyond dilation itself, the investigators identified several medications associated with increased short-term AACC risk.
Previously recognized medications included:
- Topiramate
- Hydrochlorothiazide
- Pilocarpine
- Albuterol
- Enoxaparin
- Trihexyphenidyl
Sticking with that topic: A review of drug-induced acute angle closure actually described several mechanisms by which medications can precipitate attacks, including pupillary block and ciliochoroidal effusion.
Go on …
The study also identified potential safety signals involving calcium channel blockers, CGRP monoclonal antibodies, and PCSK9 inhibitors, though the authors stressed these were observational associations—not evidence of causation.
The study also found declining use of gonioscopy over time—despite increased adoption of anterior segment optical coherence tomography (OCT) and ultrasound biomicroscopy.
To note: The American Academy of Ophthalmology's Preferred Practice Pattern continues to recommend gonioscopy as the reference standard for evaluating angle anatomy.
Got it. And were there any limitations to consider?
The study relied on EHR coding, which may not have captured every diagnostic procedure or medication exposure.
The researchers also could not consistently determine which eye was affected because laterality was often unavailable.
Medication dosage, treatment duration, adherence and concurrent medication use also could not be fully evaluated.
Finally, because this was a retrospective observational study, it could not establish cause and effect.
So what did outside experts have to say about the outcomes?
The findings align with previous evidence suggesting that pharmacologic dilation is generally safe when performed appropriately—while also reinforcing that clinicians should remain vigilant in patients with known anatomical narrow angles or other predisposing features.
The authors further noted that many of the medications associated with increased risk are prescribed outside eye care, highlighting the importance of medication reconciliation and communication between eyecare and other healthcare providers.
Anything else worth knowing?
The investigators observed that both AACC incidence and the prevalence of primary angle-closure glaucoma among affected patients increased over the study period.
They also noted that gonioscopy appeared to be underutilized before many acute events, suggesting opportunities for earlier identification of patients with anatomically narrow angles.
Lastly: the take home.
These results support the continued use of routine dilation when clinically indicated while emphasizing careful assessment of patients with anatomical risk factors and awareness of medications that may increase susceptibility.