Are Phosphodiesterase Type 5 Inhibitors Associated with Vision-Threatening Adverse Events? A Critical Analysis and Review of the Literature

Abstract

Introduction Phosphodiesterase type 5 (PDE5) inhibitors are the first line drugs for treatment of erectile dysfunction. Sildenafil (ViagraR), tadalafil (CialisR), and vardenafil (LevitraR) are from the same class of drugs that inhibit PDE5. Transient visual symptoms such as change in color perception and increased light sensitivity are well-known adverse effects of these drugs and occur in 3–11% of sildenafil users. Vision-threatening (serious) ocular complications, such as nonarteritic ischemic optic neuropathy and cilio-retinal artery occlusion have rarely been reported in PDE5 inhibitor users. Aims To highlight and analyze the most recently published case literature on serious ocular complications of PDE5 inhibitors. Methods Search of the peer-reviewed English literature was conducted using Medline. The following databases also were searched: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult. The causality assessment of the reported adverse drug reactions was analyzed by applying both the World Health Organization (WHO) Probability Scale and the criteria utilized by the National Registry of Drug-Induced Ocular Side Effects. Main Outcome Measures To scientifically and objectively find out if PDE5 inhibitors are associated with vision-threatening ocular complications. Results Eight case reports of serious PDE5 inhibitor-associated ocular complications were identified since January 2006 until February 2011. Case reports included cases of anterior and posterior nonarteritic ischemic optic neuropathy, central retinal vein occlusion, cilio-retinal artery occlusion, acute angle closure glaucoma and optic atrophy after sildenafil use. Conclusion There is lack of conclusive evidence to indicate a direct cause–effect relationship between PDE5 inhibitor use and vision-threatening ocular events. Men who use PDE5 inhibitors appear to suffer vision-threatening complications at the same frequency as the general population. However, minor visual adverse effects occur in 3–11% of users and they are transient and reversible.

Acute onset of bilateral visual loss during sildenafil therapy in a young infant with congenital heart disease

“…This enzyme is responsible for the main vascular remodelling in arterial PH, which includes vasoconstriction, smooth-muscle cells proliferation and vascular wall cells apoptosis. In addition, PDE5 decreases right ventricle contractility 4 6…”

“…As soon as the diagnosis of posterior NAION was made, sildenafil was immediately suspended, while methylprednisolone intravenously (0.5 mg/kg, four times a day) was started, as suggested in the literature 4. In addition, captopril was introduced for a better control of blood pressure, which however persisted at 90th–95th centile levels for age.…”

“…NAION has been described as a potential complication in adults on demand therapy with PDE5i for sexual dysfunction 4. Clinically, it may manifest as unilateral or bilateral visual loss, which could be either transient or permanent.…”

Neuro-ophthalmologic side-effects of systemic medications

“…Intravenous benztropine is a proposed treatment for an attack AEDs, antiepileptic drugs. inhibitors to suggest AION occurs at a higher proportion than in the general population [59][60][61]. An open label crossover study is currently underway to further define a causal link (clinicaltrials.gov identifier: NCT00867815) Antiarrhythmics Amiodarone Average drug use of 9 months prior to symptoms.…”

Toxic optic neuropathies

“…Over the last few years, an association between phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, vardenafil, or tadalafil) and anterior or posterior ischemic optic neuropathy has been suspected based on the reported cases in the literature [33,34]. The hypothesis has been a possible increase in the physiologic nocturnal hypotension with these medications, resulting in ischemia to the optic nerve head or that they might interfere with the autoregulation of blood flow, thereby decreasing the perfusion to the optic nerve head [35].…”