In a multinational cohort study of nearly 74,000 men with lower urinary tract symptoms (LUTS), men taking a daily phosphodiesterase type 5 inhibitor had a 22% higher relative risk of developing glaucoma over 5 years compared with nonusers.¹ Before we conclude that tadalafil is causing glaucoma, however, let’s ask a more fundamental question: Are we looking at a medication effect, or are we seeing the consequences of the underlying vascular disease?

The study reported that 3.93% of tadalafil users developed glaucoma over 5 years, compared with 3.16% of nonusers.¹ That’s an absolute difference of less than 1%. The increased risk was seen primarily with primary open-angle glaucoma (POAG) and ocular hypertension. Interestingly, there was no significant association with low-tension glaucoma or angle-closure glaucoma.¹ So, there is a statistical association, but an association is not the same thing as causation. 

This prompts a more interesting question: What is different about the men who need daily tadalafil in the first place? Men taking tadalafil for erectile dysfunction (ED) or LUTS frequently have the same constellation of vascular risk factors that we associate with systemic endothelial dysfunction and microvascular disease.²

In fact, ED has long been considered a potential early marker for systemic vascular disease.³ The small arteries that supply the penile tissues are particularly vulnerable to endothelial dysfunction, hypertension, arterial stiffness, and other forms of vascular compromise. That should sound familiar to anyone who manages glaucoma.

We increasingly understand glaucoma as more than simply an intraocular pressure (IOP) problem. POAG is a complex neurovascular disease in which ocular perfusion pressure, blood flow, vascular regulation, and susceptibility of the optic nerve all play important roles.⁴^,⁵ That knowledge leads me to ask whether the patients who require tadalafil already have the vascular biology that puts them at greater risk for glaucoma.

When a patient develops enough vascular dysfunction to require treatment for ED or LUTS, the same systemic factors can also affect the microcirculation that supplies the optic nerve and retina.⁴^,⁶ That doesn’t prove that these factors explain the association seen in the Hsia et al study, but it does provide a biologically plausible alternative explanation.

And this is where observational data have limitations. A large administrative database can tell us that a patient was prescribed tadalafil and subsequently developed a glaucoma diagnosis. What it cannot necessarily tell us is the degree of underlying pathology that existed before the glaucoma diagnosis. That makes it entirely plausible that at least some of the increased glaucoma risk observed in tadalafil users reflects the underlying vascular health of these patients rather than a direct toxic effect of tadalafil itself.

These findings should not prompt recommendations for patients to stop this medication. Tadalafil remains an effective and generally well tolerated treatment for both LUTS and ED. Instead, I think there is a more useful clinical takeaway: If a patient is taking daily tadalafil, it may be worth thinking about their vascular health as whole rather than just this medication.

For men over age 50, particularly those with a family history of glaucoma or other eye disease, a baseline comprehensive eye examination and regular monitoring of IOP/optic nerves are reasonable. More importantly, we should not lose sight of the bigger picture: Systemic risk factors matter for both cardiovascular health and the health of the optic nerve.

Maybe tadalafil isn’t the problem. It may simply be another clue that the vascular system has been trying to tell us something, and it’s our job to listen. OM

References

1. Hsia Y, Tsai C-Y, Hung S-C, et al. Risk of glaucoma among patients using tadalafil for lower urinary tract symptoms: a multinational cohort study. Br J Ophthalmol. 2026:bjo-2026-329957. doi:10.1136/bjo-2026-329957

2. Stasso J, Novosel O, Balas M, et al. Retinal vascular and structural changes in men with erectile dysfunction: a systematic review. Graefes Arch Clin Exp Ophthalmol. 2026. doi: 10.1007/s00417-026-07454-3

3. Jackson G, Boon N, Eardley I, et al. Erectile dysfunction and coronary artery disease prediction: evidence-based guidance and consensus. Int J Clin Pract. 2010;64(7):848-857. doi:10.1111/j.1742-1241.2010.02410.x

4. Flammer J, Orgül S, Costa VP, et al. The impact of ocular blood flow in glaucoma. Prog Retin Eye Res. 2002;21(4):359-393. doi:10.1016/s1350-9462(02)00008-3

5. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311(18):1901-1911. doi:10.1001/jama.2014.3192

6. Schmidl D, Garhofer G, Schmetterer L. The complex interaction between ocular perfusion pressure and ocular blood flow – relevance for glaucoma. Exp Eye Res. 2011;93(2):141-155. doi:10.1016/j.exer.2010.09.002

Mike Cymbor, OD, FAAO is director of the Glaucoma Institute of State College and the lead OD at Nittany Eye Associates in State College, Pennsylvania.