Patients often ask, “Can I take this medication with a glaucoma warning?” Back-of-the-box warnings generate a steady source of phone calls and extra chair time. Glaucoma patients and other prescribers are understandably cautious about using a medication that may lead to disease progression, but it is unfortunate when patients unnecessarily avoid an otherwise beneficial medication. In most cases, the answer is an easy “yes,” but there are exceptions to every rule and certain systemic medications can indeed exacerbate glaucoma. Therefore, it is helpful to discuss how to best respond to these inquiries.

Angle Closure

Many medications with a glaucoma warning pertain to patients with angle-closure disease. The concern stems from the mild amount of mydriasis that can occur with these drugs.¹ In higher risk eyes, mydriasis can increase iridotrabecular contact and/or pupillary block. Implicated medications may include, but are not limited to, the following:

Anticholinergics

Drugs with anticholinergic activity block iris sphincter contraction, resulting in passive mydriasis.¹ H₁ antagonist antihistamines are used over the counter for allergies ubiquitously. More selective second-generation antihistamines (eg, fexofenadine and cetirizine) are less likely to cause anticholinergic side effects compared to first-generation drugs like diphenhydramine. Ipratropium and tiotropium, used in chronic obstructive pulmonary disease and asthma, help relieve bronchoconstriction. Patients with urge incontinence are often prescribed oxybutynin or tolterodine to help control bladder spasms. Selective serotonin reuptake inhibitors (eg, fluoxetine and sertraline) and tricyclic antidepressants (eg, amitriptyline), which have anticholinergic properties, are widely prescribed for mood disorders.

Sympathomimetics

Alpha-1 agonists also cause mydriasis via sympathetic action on the iris dilator muscles.¹ Medications within this class, such as phenylephrine or pseudoephedrine, are primarily used as over-the-counter nasal decongestants and may be paired with an anticholinergic. Nebulized beta-2 adrenergic agents used for bronchodilation, such as albuterol or terbutaline, can inadvertently contact the ocular surface and cause mydriasis, especially when combined with ipratropium.¹

The question then becomes, “Should our patients worry about mild mydriasis?” Results from the ZAP Trial, a population-based study of at-risk primary angle closure suspects with at least 180° of iridotrabecular contact, provide added reassurance that even direct pharmacologic dilation (5% phenylephrine + 0.5% tropicamide) presents a very low risk of acute angle closure in eyes without an iridotomy (1 attack in 1,587 dilations) and even lower risk in eyes with an iridotomy (1 in 4,762 dilations).² Thus, known patients with angle closure, even those undergoing observation, can sustain mild mydriasis with minimal concern. Patients considered high risk for acute angle closure should have already undergone intervention to address their anatomy. Unfortunately, the true concern remains in the undiagnosed individual, who will not know to ask in the first place.

Steroids

Glucocorticoids are perhaps the more worrisome class of medications, as almost all forms have been found to increase intraocular pressure (IOP).³ With a long list of side effects, users or prescribers may miss the fact that steroids can increase IOP. One should be suspicious of undocumented steroid use any time IOP increases without explanation. Even seemingly benign dermatologic preparations can raise IOP if used near the eyelids.^4,5 Intranasal steroids, however, have not been conclusively shown to significantly increase IOP despite carrying a warning.³

Typically, it requires more than 2 weeks of steroid use for an increase in IOP to be seen.^3,6,7 Around one-third of the general population are steroid responders, but this rate may be as high as 90% in patients with preexisting primary open-angle glaucoma.^5-9 Thus, it’s important for patients and other providers to remain cautious when using steroids. We recommend that patients who have been prescribed any form of steroids for longer than 2 weeks should see their ophthalmologist within 4 weeks of initiating therapy. Those who have a prior history of glaucoma should be seen even earlier.^5-9

Most patients with primary open-angle glaucoma can be safely treated with a short course of steroids (less than 2 weeks) without intensive monitoring by an ophthalmologist.^5-9

Summary

For all practical purposes, warnings for medications that cause mydriasis can be disregarded for regularly monitored ophthalmology patients of any type. Conversely, physicians and patients should inform the ophthalmologist when using chronic corticosteroids. We recommend preemptively counseling patients with a simple statement: “You may find certain medications come with a glaucoma warning. It is OK to use these medications, but please let the office know if you use a steroid for more than 2 weeks.” With a few quick sentences, you can ease patient anxiety, cut back on phone calls for your staff, save chair time, and prevent patients from needlessly avoiding useful medications due to fear of worsening their glaucoma. GP

Tirth J. Shah, MD, is an ophthalmology resident at the University of Iowa Hospitals and Clinics in Iowa City, Iowa. He reports no related financial disclosures. Reach him at tirth-shah@uiowa.edu.

Lorraine M. Provencher, MD, is a glaucoma specialist at the Cincinnati Eye Institute in Cincinnati, Ohio. She reports consultancy to Allergan and Microsurgical Technology (MST), and speaker’s fees for Allergan, Ivantis, and MST. Reach her at lprovencher@cvphealth.com.

References

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2. Friedman DS, Chang DS, Jiang Y, et al. Acute angle closure attacks are uncommon in primary angle-closure suspects: the Zhongshan Angle Closure Prevention Trial. Ophthalmol Glaucoma. 2022:S2589-4196(22)00082-5.
3. Wijnants D, Stalmans I, Vandewalle E. The effects of intranasal, inhaled and systemic glucocorticoids on intraocular pressure: a literature review. J Clin Med. 2022;11(7):2007. Published 2022 Apr 3. doi:10.3390/jcm11072007
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9. Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: a review of the literature. Eye (Lond). 2006;20(4):407-416. doi:10.1038/sj.eye.6701895