Regular phosphodiesterase 5 inhibitor use in men has been found to be associated with an increased risk of ocular adverse events
Phosphodiesterase 5 inhibitor use in men is associated with an increased risk of developing adverse ocular events including serous retinal detachment (SRD, retinal vascular occlusion (RVO) and ischaemic optic neuropathy (ION). This was the finding of an analysis of a US private health claims database by researchers from Collaboration for Epidemiology of Ocular Diseases, Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, Canada.
The phosphodiesterase 5 inhibitor (PDE5I) drugs have revolutionised the management of erectile dysfunction in men. While the condition is not an inevitable consequence of the aging process, the prevalence increases from around 5.1% in 20 to 39-year-old men to 70.2% in men 70 years of age and older. The first agent to be made available was sildenafil and there are currently three other marketed agents, vardenafil, tadalafil and avanafil. Although adverse ocular events such as transient blue discolouration and increased brightness have been reported with these drugs, one critical analysis of the literature concluded that there was a lack of conclusive evidence to indicate a direct cause-effect relationship between phosphodiesterase 5 inhibitor and vision-threatening ocular events.
Since most of the data on adverse optic events has arisen through case reports, for the present study, the Canadian team sought to quantify the risks of SRD, RVO and ION associated with the use of phosphodiesterase 5 inhibitors.
Using the PharMetrics Plus database the team identified a cohort of new PDE5I users and excluded all cases where SRD, RVO and ION had been diagnosed in the year prior to initiation of the drugs. Male users were then followed up until the development of one of the three adverse events occurred and which was set as the composite primary outcome. For each PDE5I, the researchers age-matched 4 control, non-users, who entered the database at the same time.
Phosphodiesterase 5 inhibitor use and adverse ocular events
The PDE5I cohort included 213,033 individuals with a mean age of 64.6 years and who were followed-up for a mean of 3.8 years. Among PDE5I users, co-morbidities included hypertension (24.6%), diabetes (38.1%) and coronary artery disease (36.1%) and 9.8% were smokers.
After adjustment for co-morbidities, PDE5I use was associated with a higher incidence of all three (SRD, RVO, ION) adverse ocular events (incidence rate ratio, IRR = 1.85, 95% CI 1.41 – 2.42). Moreover, when considered separately, each of the outcomes was also independently associated with a higher risk among PDE5I users compared to non-users. For example, the IRR for SRD, RVO and ION were 2.58, 1.44 and 2.02 respectively.
While the use of PDE5I appeared to be associated an increased risk of adverse ocular events, the actual incidence was low, with 15.5 cases per 10,000 person years for the composite outcome and, for example, 3.8 cases 10,000 person years for SRD.
The authors concluded that their findings suggested that men who were regular users of PDE5I should be cognisant of any adverse ocular events and to alert their physician if they experience any visual problems.
Etminan M et al. Risk of Ocular Adverse Events Associated With Use of Phosphodiesterase 5 Inhibitors in Men in the US JAMA Ophthalmol 2022