The relationship between systemic medications and glaucoma is an important clinical issue because glaucoma patients often have comorbidities such as hypertension, diabetes, and depression3)4).
The effects of systemic medications on glaucoma can be classified into the following three categories.
| Category | Representative Medications |
|---|---|
| Increased Risk | Steroids, topiramate |
| Decreased Risk | Beta-blockers, metformin |
| Conflicting reports | CCB, SSRI |
Systemic drugs that can induce acute angle-closure glaucoma (AACG) include nebulized bronchodilators (ipratropium bromide, salbutamol), SSRIs, tricyclic antidepressants, muscle relaxants, illicit stimulants, and other anticholinergics and sympathomimetics 2)3). Topiramate and sulfonamide drugs cause acute angle closure by a posterior pushing mechanism due to uveal effusion 2)3).
Systemic hypertension has been reported as a risk factor for open-angle glaucoma, but there is inconsistency among studies 3)4). It has been suggested that excessive blood pressure reduction by antihypertensive drugs may impair optic nerve perfusion and increase glaucoma risk 3)4). Type 2 diabetes is also a risk factor for open-angle glaucoma, with a two-fold odds ratio reported in non-Hispanic whites 4).
The mechanisms by which systemic drugs affect glaucoma can be divided into four main categories: (1) increased resistance to aqueous humor outflow through the trabecular meshwork (steroid-induced ECM deposition), (2) forward displacement of the lens-iris diaphragm due to ciliary body edema or uveal effusion (topiramate, sulfonamides), (3) pupillary block and angle closure due to mydriasis (anticholinergics, sympathomimetics) 2)3), and (4) mechanical angle closure due to spontaneous suprachoroidal hemorrhage (anticoagulants). Conversely, beta-blockers reduce aqueous humor production by inhibiting sympathetic receptors on the ciliary epithelium, thereby lowering intraocular pressure.
Drug-induced acute angle-closure glaucoma presents with acute eye pain, headache, decreased vision, blurred vision, halos around lights, and vomiting. Steroid-induced glaucoma is characterized by a chronic elevation of intraocular pressure without subjective symptoms, which may lead to delayed detection.
Acute angle-closure type: Conjunctival injection, corneal edema, shallow anterior chamber, dilated fixed pupil, and marked intraocular pressure elevation (40–60 mmHg or higher) are observed.
Open-angle type (steroid-induced): Intraocular pressure elevation with an open angle. Long-term use leads to progressive optic disc cupping and visual field loss. Intraocular pressure elevation typically occurs within 3–6 weeks after starting steroids, but tends to normalize within one month after discontinuation.
Increased risk of open-angle glaucoma
Corticosteroids: Decreased expression of trabecular meshwork mucin-2/9 → increased ECM deposition → increased aqueous outflow resistance. Particularly high risk in patients with a family history of open-angle glaucoma.
Risk by route of steroid administration: In addition to systemic administration (oral, intravenous), topical, subconjunctival, and intravitreal administration also carry a risk of elevated intraocular pressure.
Increased risk of angle-closure glaucoma
Topiramate/Sulfonamides: Induce acute angle closure via posterior pressure mechanism due to uveal effusion 2)3). Normalizes upon drug discontinuation.
Anticholinergics: Inhibition of iris muscarinic receptors → mydriasis → pupillary block. High risk with topical administration.
Nebulized bronchodilators: Nebulized inhalation of ipratropium bromide and salbutamol can trigger angle closure 2)3).
Anticoagulants: Spontaneous suprachoroidal hemorrhage → forward displacement of the lens-iris diaphragm → angle closure.
Drug-induced angle closure usually occurs in eyes with anatomical predisposition such as shallow anterior chamber 3). Acute angle closure can also occur during or after general anesthesia 2)3).
Patients with type 2 diabetes have an increased risk of primary open-angle glaucoma 4)5). Microvascular changes in the optic nerve are thought to increase susceptibility to optic neuropathy 4). The association between systemic hypertension and glaucoma is debated, but excessive treatment with antihypertensive drugs may increase glaucoma risk via low diastolic perfusion pressure 3)4).
Migraine and peripheral vasospasm (Raynaud’s phenomenon) may also be progression factors for glaucoma through impaired autoregulation of optic nerve head blood flow 4).
For the diagnosis of drug-induced glaucoma, a detailed medication history is most important.
Tonometry: Precise measurement using Goldmann applanation tonometry. Comparison before and after medication changes is useful.
Gonioscopy: Assess the presence of angle closure and the extent of peripheral anterior synechiae (PAS).
Anterior segment OCT: Quantitative evaluation of anterior chamber depth and angle structures.
Visual field testing and OCT: Evaluation of optic nerve damage in steroid-induced glaucoma. Standard automated perimetry and RNFL thickness measurement.
Diagnostic pupillary dilation is safe in the general population, and the risk of missing retinal disease due to not dilating is greater than the risk of inducing angle closure2)3). In patients with known angle closure who have received appropriate prophylactic treatment (patent iridotomy), dilation is usually safe3).
Discontinuation or change of the causative drug is most important. In topiramate/sulfonamide-induced acute angle-closure glaucoma, intraocular pressure normalizes after discontinuation of the causative drug2)3). In steroid-induced glaucoma, consider changing the route of administration (systemic to topical), switching to a lower-potency steroid, or discontinuing.
Treatment of acute angle-closure attack: Intravenous hyperosmotic agents (mannitol, glycerol) to reduce acute intraocular pressure elevation1). Combine with aqueous suppressants (oral acetazolamide, beta-blocker eye drops)1). However, in sulfonamide-induced acute angle-closure glaucoma, avoid acetazolamide.
Laser peripheral iridotomy (LPI): Performed for angle closure involving pupillary block. May be ineffective in drug-induced angle closure due to posterior pushing mechanism from uveal effusion.
Treatment of steroid-induced glaucoma: Managed with intraocular pressure-lowering eye drops. In chronic cases where intraocular pressure does not normalize after steroid discontinuation, consider surgical treatment1).
Increased trabecular outflow resistance (open-angle type): Steroids suppress the expression of myocilin-2/9 in the trabecular meshwork and increase the deposition of ECM (fibronectin, myocilin). The formation of CLANs (cross-linked actin networks) also contributes to mechanical changes in the trabecular meshwork microstructure. These increase aqueous humor outflow resistance, leading to open-angle type intraocular pressure elevation.
Posterior pushing mechanism (angle-closure type): Topiramate and sulfonamides induce ciliary body edema. The lens-iris diaphragm shifts forward, mechanically occluding the angle. This differs from the conventional pupillary block mechanism, so LPI may be ineffective.
Pupillary block mechanism (angle-closure type): Mydriasis caused by anticholinergics and sympathomimetics changes the contact area between the iris and lens, inducing pupillary block. The risk is particularly high in eyes with anatomically shallow anterior chambers2)3).
Suprachoroidal hemorrhage (angle-closure type): Spontaneous suprachoroidal hemorrhage can occur in patients using anticoagulants. Detachment of the choroid and retina due to hemorrhage pushes the lens-iris diaphragm forward, secondarily occluding the angle.
Beta-blockers: Inhibit beta receptors on the ciliary epithelium, reducing aqueous humor production. Non-selective beta-blockers have a greater ocular hypotensive effect than cardioselective beta-blockers.
Metformin: Reported to reduce the risk of developing open-angle glaucoma by 25% through suppression of mitochondrial dysfunction, prevention of fibrosis, and inhibition of angiogenesis and inflammation.
Statins: eNOS upregulation → increased NO → vasodilation → improved optic nerve perfusion. Neuroprotective effects via reduction of retinal ganglion cell apoptosis have also been reported.
Steroids suppress the expression of myocilin-2/9 in the trabecular meshwork and inhibit the degradation of ECM proteins (fibronectin, myocilin). This increases ECM deposition in the trabecular meshwork, raising aqueous humor outflow resistance. Additionally, CLANs formation alters the trabecular meshwork microstructure, contributing to increased resistance. As a result, chronic open-angle type intraocular pressure elevation occurs. Intraocular pressure elevation typically appears 3 to 6 weeks after starting steroids and tends to normalize within one month after discontinuation. However, with chronic or long-term use, it can become permanent.
The following research trends are noteworthy regarding the association between systemic medications and glaucoma.
When prescribing systemic medications to glaucoma patients, the following points require attention. (1) For patients with predisposing factors for angle closure, ophthalmology consultation should be obtained before prescribing topiramate, anticholinergics, SSRIs, or nebulized bronchodilators 2)3). (2) During long-term steroid use, regular intraocular pressure monitoring should be performed, and switching to a lower potency steroid should be considered as needed. (3) Since excessive use of antihypertensive drugs leading to low perfusion pressure can be a risk for glaucoma progression, setting appropriate blood pressure targets is important 3)4). (4) In patients taking oral beta-blockers, an intraocular pressure reduction of about 1 mmHg can be expected, but the additive effect with topical beta-blockers is limited.
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- European Glaucoma Society. Terminology and Guidelines for Glaucoma, 5th Edition. PubliComm, 2020.
- European Glaucoma Society. Terminology and Guidelines for Glaucoma, 6th Edition. Br J Ophthalmol. 2025.
- American Academy of Ophthalmology. Primary Open-Angle Glaucoma Preferred Practice Pattern®. 2020.
- American Academy of Ophthalmology. Primary Open-Angle Glaucoma Suspect Preferred Practice Pattern®. 2020.
