Erectile Dysfunction Drugs Linked to Lower Glaucoma Risk in Men

DENVER — Men using phosphodiesterase type 5 (PDE-5) inhibitors for erectile dysfunction (ED) had a modestly lower risk of glaucoma, according to a study reported here.

During 3 years of follow-up, men taking PDE-5 inhibitors had a reduced likelihood for glaucoma suspect (risk factors) and open-angle glaucoma (OAG). The absolute difference ranged from 1-3% for glaucoma suspect and about 1% for OAG. The relative risk differential achieved statistical significance each year for both conditions (P=0.04 to P<0.01).

“The association is likely vascular in origin, as PDE-5 inhibitors enhance [nitric oxide-cyclic guanosine monophosphate] signaling, improving ocular blood flow and optic nerve perfusion,” concluded Abdelrahman M. Elhusseiny, MD, of the University of Miami, and colleagues in a poster presentation at the Association for Research in Vision and Ophthalmology (ARVO) meeting. “PDE-5 inhibitors do not produce sustained intraocular pressure reduction, suggesting the effect is not mediated by aqueous humor dynamics. Further prospective studies are needed to clarify mechanisms, evaluate long-term effects, and determine clinical implications.”

PDE-5 inhibitors (such as sildenafil [Viagra], tadalafil [Cialis], and vardenafil [Levitra]) are prescribed primarily for ED and pulmonary hypertension, but the drugs’ vascular and cryoprotective effects may have broader therapeutic implications, the investigators noted. To examine the issue, they queried the TriNetX clinical network for the years 2005-2025 to identify men at least 40 years old with diagnosed ED, and then grouped them according to history of PDE-5 inhibitor use.

The primary analysis included two propensity-matched groups of 23,603 men each (PDE-5 users and non-users). Mean follow-up in each group was almost 1,000 days. The primary endpoints were glaucoma suspect and OAG.

After a year of follow-up, rates of glaucoma suspect and OAG were 6.49% and 2.13% versus 9.73% and 3.22% for PDE-5 inhibitor users and non-users, respectively (P<0.01 for both comparisons). Rates of both conditions increased in both groups and between-group differences shrank during the next 2 years. At the end of follow-up, rates of glaucoma suspect and OAG were 11.17% and 3.88% among PDE-5 inhibitor users versus 12.06% (P=0.01) and 4.28% (P=0.04) among non-users.

Higher HDL Linked to Lower AMD Risk in Women

Higher levels of high-density lipoprotein (HDL) in women were associated with a small but statistically significant lower risk of developing neovascular age-related macular degeneration (nAMD), according to a study reported at ARVO.

Women with HDL levels ≥60 mg/dL had a 1% absolute difference in nAMD (10.2% vs 11.2%) with women who had low HDL (<50 mg/dL). The difference translated into a 9% reduction in relative risk (95% CI 0.83-0.99, P=0.03). However, the difference no longer remained significant in a time-to-event analysis (HR 0.93, 95% CI 0.85-1.02, P=0.11). A comparison of low versus normal HDL (50-59 mg/dL) showed no difference, and neither high nor low HDL levels altered nAMD risk in men.

“These findings suggest there may be sex-specific, lipid-related mechanisms involved in AMD progression, and highlight the need for further research into the role of HDL and retinal disease biology,” said Adriana Kaganovski, of SUNY Downstate Health Sciences University in New York City, in a recorded summary of the study.

Lipid metabolism has been implicated in AMD pathogenesis but the influence of HDL on AMD risk remains unclear, said Kaganovski. To examine whether sex-specific HDL categories are associated with AMD risk, investigators searched the TriNetX network to identify adults with diagnosed nAMD and HDL measurements within 6 months of diagnosis. Men and women were stratified by sex-specific HDL levels for comparisons of high versus low and low versus normal levels.

Data analysis involved matched cohorts (4,347 to 8,911 participants each) to compare nAMD prevalence by HDL levels in men and women. For men, nAMD prevalence was 9-10% regardless of HDL level. Among women, nAMD prevalence was about 10-11%, and only the comparison of high versus low HDL produced a statistically significant difference.

Statin Use and Glaucoma Risk

Previously documented neuroprotective effects of statins may extend to glaucoma, according to a retrospective analysis involving more than 500,000 patients.

Statin use was modestly associated with the 5-year incidence of OAG (5.0% vs 5.3%, P<0.001). In a separate analysis of glaucoma-associated surgery, reflecting progressive disease, statin users had significantly lower hazards for incisional surgery, minimally invasive glaucoma surgery (MIGS), and selective laser trabeculoplasty (SLT).

“Our results are consistent with our hypothesis that statin use is associated with lower risk of glaucoma onset and progression,” concluded Forest Lin, of the University of South Florida in Tampa, and colleagues in a poster presentation. “Prospective trials are needed to further elucidate the relationship between statin usage and glaucoma.”

Statins’ neuroprotective potential in glaucoma remains poorly understood, as previous studies have yielded inconsistent results, the investigators noted. To inform the issue, they tested the hypothesis that statin use would be associated with a decreased risk of OAG and progressive disease, as reflected in surgery and other interventions.

A search of the TriNetX database produced matched cohorts of 218,677 patients each for the analysis of glaucoma incidence and matched cohorts of 51,551 patients each for the analysis of progressive disease.

Over a 5-year period, 10,223 statin users and 10,801 non-users had new diagnoses of OAG, a difference that translated into a 9% reduction in the hazard ratio (95% CI 0.89-0.94). Statin use was associated with larger reductions in HRs for incisional surgery (HR 0.83, 95% CI 0.78-0.88), MIGS (HR 0.82, 95% CI 0.78-0.87), and SLT (HR 0.88, 95% CI 0.84-0.92). Statin users were more likely to be treated with ocular hypotensive agents (HR 1.39, 95% CI 1.37-1.41).