PDE-5 Inhibitors May Protect Against Glaucoma Development

While the potential protective mechanism of PDE-5 inhibitor therapy against open-angle glaucoma remains unelucidated, researchers believe the association is related to vascular or perfusion-related mechanisms affecting the optic nerve head. Click image to enlarge. Phosphodiesterase-5 inhibitors (PDE-5i) are a class of systemic agents that enhance endogenous nitric oxide signaling to relax smooth muscles and increase blood flow. While primarily prescribed for the treatment of erectile dysfunction (ED) and pulmonary arterial hypertension, a growing body of evidence suggests these drugs may have therapeutic benefits for other disorders characterized by impaired microvascular perfusion, including glaucoma. To investigate, a new study evaluated the association between PDE-5i therapy and the development of glaucoma suspect status or open-angle glaucoma in a cohort of men with ED. The multicenter, retrospective cohort study used deidentified electronic health records of men aged 40 or older with ED. The development of glaucoma suspect or open-angle glaucoma at one, two and three years was compared between men who received PDE-5i therapy (n=40,676) and those with no exposure (n=32,415). The average age at index was 61.8 ±10.2 years in the PDE-5i group and 64.3 ±11.9 years in non-users.After propensity score matching, the data showed that compared to non-users, fewer men receiving PDE-5i therapy developed glaucoma suspect status at one year (6.49% vs. 9.73%), two years (9.27% vs. 10.86%) and three years (11.17% vs. 12.06%). PDE-5i users also had a lower rate of open-angle glaucoma development at all three time intervals compared to non-users (one year: 2.13% vs. 3.22%; two years: 3.00% vs. 3.80%; three years: 3.88% vs. 4.28%). Cox proportional hazards models further confirmed the robustness of these associations.“The mechanism underlying the reduced glaucoma hazard observed in this study remains uncertain,” the researchers explained in their paper on the study, published in American Journal of Ophthalmology. “One biologically plausible explanation relates to the vascular effects of PDE-5 inhibition,” they noted, clarifying that “PDE-5 inhibitors enhance nitric oxide-cGMP signaling and produce vasodilatory effects within the ocular circulation.” Experimental studies have also demonstrated “that sildenafil increases choroidal capillary diameter in animal models, reflecting a pronounced hemodynamic response,” the researchers added.Since prior research has shown that PDE-5 inhibitors have no significant or lasting effects on intraocular pressure measurements, this suggests that “the association observed in our study is unlikely to be mediated through direct effects on aqueous humor dynamics,” the researchers pointed out. Rather, they posited, “any potential influence of PDE-5 inhibition on glaucoma risk is more plausibly related to vascular or perfusion-related mechanisms affecting the optic nerve head.”The authors acknowledge several limitations of their study, including its retrospective observational nature, which prevented their ability to draw causal conclusions. Moreover, detailed ophthalmic parameters were not available to assess glaucoma severity or progression. The study’s reliance on prescription records also precludes the confirmation of adherence, dosing and cumulative exposure to PDE-5i therapy.“Prospective studies are needed to clarify exposure-response relationships, assess long-term effects and determine the clinical implications of PDE-5 inhibition for glaucoma risk reduction and management,” the authors concluded.Click here for the journal source. Elhusseiny AM, Abboud I, Almobayed A, Medeiros FA. Association between PDE-5 inhibitor therapy and the hazard of open-angle glaucoma. Am J Ophthalmol. April 12, 2026. [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.