Abstract
Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra® (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. It also exerts minor inhibitory action against PDE6, which is present exclusively in rod and cone photoreceptors. The effects of sildenafil on the visual system have been investigated in a wide variety of clinical and preclinical studies due to the fact that a high dose of sildenafil may cause mild and transient visual symptoms in some patients. A literature review was performed using PubMed, Cochrane Library and Clinical Trials databases from 1990 up to 2020, focusing on the pathophysiology of visual disorders induced by sildenafil. The aim of this review was not only to gather and summarize the information available on sildenafil clinical trials (CTs), but also to spot subpopulations with increased risk of developing undesirable visual side effects. This PDE inhibitor has been associated with transient and reversible ocular side effects, including changes in color vision and light perception, blurred vision, photophobia, conjunctival hyperemia and keratitis, and alterations in the electroretinogram (ERG). Sildenafil may induce a reversible increase in intraocular pressure (IOP) and a few case reports suggest it is involved in the development of nonarteritic ischemic optic neuropathy (NAION). Reversible idiopathic serous macular detachment, central serous retinopathy and ERG disturbances have been related to the significant impact of sildenafil on retinal perfusion. So far, sildenafil does not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors as long as the therapeutic dose is not exceeded and is taken under a physician’s direction to treat a medical condition. However, the recreational use of sildenafil can lead to harmful side effects, including vision changes.
Highlights
Given that sildenafil nonselective inhibition of retinal phosphodiesterase 6 (PDE6) results in visual disturbances, several reports have questioned the ocular safety of this drug over the last two decades [11,53,64,72,73]
The remaining 20% is divided between pulmonary arterial hypertension (PAH) (10%), chronic open-angle glaucoma (COAG) (5%), and ischemic stroke (IS) (5%) patients (Figure 2b and Table 3)
Phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil are often used for the treatment of erectile dysfunction (ED) and PAH
Summary
Homeostasis within the photoreceptor, K+ and Ca2+ are, in parallel, continuously extruded via the potassium-dependent sodium-calcium exchanger (NCKX). This constant inward current, referred to as the dark current, causes photoreceptor depolarization and glutamate release at the synaptic terminal, inhibiting postsynaptic second-order neurons (bipolar cells). Absorption of photons by rhodopsin leads to the sequential activation of G-protein transducin and phosphodiesterase 6 (PDE6), responsible for the hydrolysis of cGMP and the consequent closure of CNG channels. This interrupts the dark current, resulting in the Biomedicines 2021, 9, 291.
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