Nitrates May Protect Against Glaucoma, Study Suggests

A recent American Journal of Ophthalmology study reveals a potential protective role of chronic oral nitrate use against open-angle glaucoma (OAG). Analyzing real-world data, researchers found that long-term nitrate use was associated with a significantly lower risk of OAG and primary open-angle glaucoma at three and five years, but had no effect at one year. This suggests nitrates may influence glaucoma pathogenesis beyond IOP reduction. Photo: Michael Chaglasian, OD. Click image to enlarge. Research has uncovered certain systemic medications may contribute to glaucoma risk modulation, such as beta blockers, glucagon-like peptide 1 receptor agonists, metformin and statins, to name a few. Nitrates—a class that includes nitroglycerin, isosorbide mononitrate and isosorbide dinitrate—have become a more widely used therapy in chronic ischemic heart disease (IHD) management, helping to release nitric oxide (NO). Given their ability to regulate ocular blood flow and intraocular pressure (IOP) dynamics, interest is growing in the potential of NO-based therapies to manage glaucoma, but the association between their use and disease risk remains uncertain. New research published in American Journal of Ophthalmology systematically investigated chronic oral nitrate use and the risk of open-angle glaucoma (OAG) and ocular hypertension (OHT) with real-world data. The findings suggest a potential protective role for nitrates.This retrospective cohort study used anonymized patient data from 30,937 patients in the TriNetX database. Those 40 years or older with a diagnosis of chronic IHD were included, and the cohort was divided into two groups: those with documented evidence of at least four refill prescriptions for nitrates prior to the index date and those who had never been prescribed nitrates. Mean age was approximately 69 years; over 72% non-Hispanic whites were the majority of each group.According to the results of the study, chronic nitrate use was associated with a significantly lower risk of OAG at three years (1.18% vs. 1.27%) and five years (1.84% vs. 2.18%). The risk of POAG was also reduced at three years (0.96% vs. 1.07%) and five years (1.44% vs. 1.78%). This protective effect was not observed at the one-year mark. However, patients in the nitrate group were also less likely to require first-line glaucoma therapy at one year (2.10% vs. 2.53%), three years (2.99% vs. 3.55%) and five years (4.59% vs. 5.27%).No significant association was observed between nitrate use and OHT risk at any time point, noted the study authors. These findings imply that the protective effects of nitrates may extend beyond lowering IOP, wrote the authors. “This supports the growing body of evidence indicating that glaucoma pathogenesis involves not only elevated IOP but also vascular dysregulation and impaired optic nerve perfusion,” they continued. “Nevertheless, it remains possible that oral nitrates could still exert a protective effect by lowering IOP in the normal-tension glaucoma group or modulating diurnal IOP fluctuations, even if the overall incidence of OHT remains unchanged. Further studies are warranted to investigate these possibilities.”Researchers offered several biological mechanisms that may contribute to this. “Nitric oxide-mediated vasodilation improves ocular perfusion, reducing ischemic damage to the optic nerve head,” the authors wrote in their paper. “Chronic oral nitrate therapy has been associated with significant retinal venous dilation, suggesting enhanced ocular blood flow that may protect against glaucomatous damage. Additionally, NO exerts direct neuroprotective effects by  modulating glutamate-mediated excitotoxicity, which has been suggested to be a key contributor  to retinal ganglion cell apoptosis in glaucoma.”This study did not find an association between nitrate use and the development of OHT, “which may be attributed to the modest effect of nitrates on IOP reduction suggested in some studies. Evidence on this relationship remains inconclusive,” they continued. “While this study establishes an association between oral nitrate use and reduced glaucoma risk, causal inferences cannot be drawn without prospective validation in randomized controlled trials,” concluded the authors. “These results lay the foundation for future research into NO-based therapeutics in glaucoma, positioning oral nitrate therapy as a potential adjunct in glaucoma management. Prospective cohort studies and randomized clinical trials are needed to assess whether oral nitrate therapy influences glaucoma progression and visual function over time.”Click here for the journal source. Elhusseiny, Abdelrahman M. et al. Association between chronic oral nitrate use and the risk of ocular hypertension and open-angle glaucoma. American Journal of Ophthalmology. July 18, 2025. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.