Persistent Visual Toxicity Following High Dose of Sildenafil Citrate

Introduction

A recent case report published in *Retinal Cases and Brief Reports* discusses persistent visual toxicity stemming from a high dose of sildenafil citrate. Commonly known as Viagra, sildenafil citrate is prescribed for erectile dysfunction, pulmonary hypertension, and used off-label for conditions such as Raynaud phenomenon. Typical dosages range from 25 to 100 milligrams.

Mechanism of Action

Sildenafil citrate functions by inhibiting phosphodiesterase-5 (PDE-5), an enzyme located in the smooth muscle of blood vessels. This inhibition leads to relaxation of blood vessels, promoting increased blood flow.

Vision Problems Linked to Sildenafil Citrate

In addition to PDE-5, sildenafil citrate also inhibits phosphodiesterase-6 (PDE-6), which is found in the retina. Although the effect on PDE-6 is significantly less—approximately 10% of that on PDE-5—this inhibition can lead to visual side effects. Cone photoreceptor cells are particularly vulnerable to the effects of PDE-6 inhibition.

Visual Side Effects

The visual side effects associated with sildenafil citrate include color vision alterations, heightened brightness perception, blurred vision, light sensitivity, and temporary changes in electroretinogram results. These effects tend to be dose-dependent, with higher doses correlating with an increased likelihood of persistent side effects. Generally, side effects experienced at recommended doses resolve within 24 hours.

Case Report Overview

Patient Profile

The recent case report describes a 31-year-old male who ingested a high dose of sildenafil citrate, resulting in ongoing visual disturbances. The drug was acquired from an online source in liquid form, and the patient did not accurately measure the dosage with the provided measuring device, leaving the exact amount ingested unknown.

Symptoms and Medical Attention

Shortly after taking the high dose, the patient experienced erythropsia, characterized by red-tinted vision in both eyes, along with reduced contrast sensitivity. Additionally, he reported experiencing multicolored flashes of light, which subsided within approximately 24 hours. After two days of persistent red-tinted vision and decreased contrast, he sought medical assistance. Six months post-ingestion, optical tests revealed dark spots on the retina, indicative of photoreceptor cone loss.

Related Findings

This case report echoes findings from a 2017 study published in JAMA Ophthalmology, where a patient who consumed 750 milligrams of sildenafil citrate exhibited similar visual side effects. Electroretinogram testing in that case also indicated significant damage to cone photoreceptors. Remarkably, visual functions returned to normal after a year of ongoing symptoms. Preclinical studies conducted by Pfizer, the manufacturer of Viagra, found that 50% of participants experienced visual disturbances at doses of 200 milligrams—double the recommended amount.

Genetic Susceptibility to Visual Disturbances

Animal Studies

Research involving mice has identified a gene that may indicate a higher risk for visual disturbances from sildenafil citrate. Mice carrying rd1 genes, linked to retinitis pigmentosa, showed increased susceptibility to visual toxicity from PDE-6 inhibition. In experiments, mice with the rd1 gene did not recover from the visual toxicity, while those without the mutation returned to normal after 48 hours. Approximately 2% of the human population carries this gene mutation, potentially explaining why certain individuals are more prone to visual disturbances when using sildenafil citrate.

Limitations of the Case Report

In this case report, the high dose of sildenafil citrate was identified as the primary cause of the patient’s visual toxicity. The findings are consistent with earlier reports and preclinical data. However, a limitation of the case is the lack of purity testing of the liquid sildenafil citrate purchased online, leaving open the possibility that the patient may have been exposed to additional contaminants affecting his vision.

Conclusion

This case serves as a pertinent reminder of the potential risks associated with high doses of sildenafil citrate, particularly concerning visual health. Further research is essential to understand the mechanisms of toxicity and identify at-risk populations.

References

Yanoga F, Gentile RC, Chui TYP, et al. Sildenafil Citrate Induced Retinal Toxicity-Electroretinogram, Optical Coherence Tomography, and Adaptive Optics Findings. Retin Cases Brief Rep. 2018.
Wolters Kluwer Clinical Drug Information, Inc. (Lexi-Drugs). Wolters Kluwer Clinical Drug Information, Inc.; October 11, 2018.