Significance of Drug-Induced Angle-Closure Glaucoma

The authors used the FDA Federal Adverse Event Reporting System (FAERS) to identify "a total of 11,737,133 adverse events, of which 1629 reports were related to angle-closure glaucoma." Angle-closure glaucoma reports identified 611 suspected drugs. Disproportionality analysis was performed "to explore the connection between adverse effects of angle-closure glaucoma and all drugs within the FAERS database." The results showed that most of the cases originated from the US (33.39%) and that there were more female (66.05%) than male (23.63%) participants with angle-closure glaucoma. Sulfonamides (642 reports), particularly topiramate (520 reports), had the highest number of reports of adverse effects, followed by serotonergic agents (318 reports), specifically selective serotonin reuptake inhibitors (SSRIs; 239 reports). Tropicamide, an anti-muscarinic agent, "exhibited the most robust statistical significance among all drugs associated with angle-closure glaucoma (n = 18), whereas acetazolamide demonstrated the second strongest association (n = 51)."

"FAERS cannot definitively ascertain whether the identified drugs directly cause the onset of disease." The authors acknowledged that their findings regarding sulfonamides, anti-muscarinic agents, and sympathomimetic agents had previously been described; however, their review revealed that olanzapine, phentermine, and ranibizumab are positively correlated with angle-closure glaucoma. The authors hypothesized that olanzapine, owing to its mild anti-cholinergic effects, can "trigger or worsen angle-closure glaucoma." Unfortunately, the authors did not provide empirical data to support this. Asaoka et al have shown that olanzapine "enhances the SSRI-induced increase in extracellular serotonin (5-hydroxytryptamine) levels" when olanzapine is used in combination with SSRIs.¹ Furthermore, Aftab et al provided tepid evidence that ranibizumab alone can trigger angle-closure glaucoma. Hoguet et al, in their review of the PubMed and Cochrane databases, stated that "further studies are needed to determine at-risk populations" since it is well-known that some eyes that undergo intravitreal anti-VEGF injections are prone to experience a rise in intraocular pressure.²

The authors clearly showed that clinicians should be cognizant that patients with narrow angles taking sulfonamides, SSRIs, sympathomimetic agents, olanzapine in combination with an SSRI, or phentermine-topiramate are at high risk of developing angle-closure glaucoma.³ The evidence that olanzapine, ranibizumab, or phentermine alone can cause angle-closure glaucoma is weak. Further work needs to be done to "identify specific drug adverse events and patient profiles susceptible to angle-closure glaucoma."

References

1. Asaoka N, Nagayasu K, Nishitani N, et al. Olanzapine Augments the Effect of Selective Serotonin Reuptake Inhibitors by Suppressing GABAergic Inhibition via Antagonism of 5-HT₆ Receptors in the Dorsal Raphe Nucleus. Neuropharmacology. 2015;95:261–268. https://www.sciencedirect.com/science/article/abs/pii/S0028390815001240?via%3Dihub
2. Hoguet A, Chen PP, Junk AK, et al. The Effect of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure and Glaucoma: A Report by the American Academy of Ophthalmology. Ophthalmology. 2019;126(4):611–622. https://www.aaojournal.org/article/S0161-6420(18)33065-3/fulltext
3. Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024;332(7):571–584. https://jamanetwork.com/journals/jama/article-abstract/2821290