Phosphodiesterase Type-5 Inhibitors and Glaucoma

Phosphodiesterase type-5 (PDE5) inhibitors are widely prescribed for erectile dysfunction and exert their pharmacologic effects through augmentation of nitric oxide-cyclic guanosine monophosphate signaling, a pathway with important ocular vascular implications. Given the expression of PDE5 within ocular tissues, increasing attention has been directed toward the effects of these agents on intraocular pressure (IOP), ocular blood flow, and glaucoma-related outcomes. Most clinical and experimental studies evaluating PDE5 inhibitors demonstrate no clinically meaningful or sustained effect on IOP across a range of dosing regimens, exposure durations, and patient populations, including individuals with established open angle glaucoma. Although isolated studies have reported transient or modest IOP elevations, these changes were typically small, transient, and unlikely to be clinically significant. In contrast, substantial evidence indicates that PDE5 inhibition increases ocular blood flow, with effects that appear more pronounced in the choroidal circulation than in the retinal vasculature. Human and animal studies have consistently demonstrated increased choroidal perfusion and thickness after sildenafil administration, supporting a preferential choroidal vascular response. Regarding glaucoma, early concerns were largely based on isolated case reports and postmarketing observations. More recent large-scale observational analyses suggest that PDE5 inhibitor exposure is associated with a lower hazard of being diagnosed as a glaucoma suspect or with open angle glaucoma. Collectively, current evidence supports a neutral effect of PDE5 inhibitors on IOP, a consistent enhancement of choroidal blood flow, and a potential protective association with glaucoma, warranting further mechanistic and prospective investigation. In this review, we examine the available clinical and experimental evidence regarding the effects of PDE5 inhibitors on IOP, ocular perfusion, and glaucoma risk to clarify their ophthalmic safety profile and potential therapeutic implications.