Nonarteritic anterior ischemic optic neuropathy (NAION) occupies an uncomfortable position in clinical medicine: it is simultaneously rare, feared, poorly understood, and frustratingly unpredictable. For a condition capable of permanently altering vision within hours, the scientific community has long sought to uncover why NAION occurs and whether common medications could influence its incidence. Among the many therapeutic agents examined, sildenafil citrate — a selective phosphodiesterase type 5 (PDE5) inhibitor widely used for erectile dysfunction (ED) — has received unusual scrutiny.

The question fueling debate is simple: Does sildenafil increase the risk of NAION?

The answer, as always in medicine, is less straightforward — but far more interesting. Drawing on pooled epidemiologic data, global clinical trials, and a careful analysis of underlying risk factors, the evidence suggests that the connection between sildenafil and NAION is, at best, coincidental. At worst, it is the product of overlapping risk profiles rather than drug-induced ocular injury.

This article provides a deep, clinically grounded review of the topic, integrating available data into a structured, readable, yet academically rigorous narrative.

Understanding NAION: A Condition of Vascular Vulnerability

NAION represents the most common acute optic neuropathy in adults aged 50 and older. Despite this distinction, it remains an uncommon diagnosis, with an estimated 1500–6000 cases annually in the United States. The condition is characterized by sudden, painless, unilateral visual loss, typically occurring upon awakening — a detail that has sparked more hypotheses about nocturnal blood pressure dips than any retina specialist may care to remember.

At its core, NAION is believed to stem from an ischemic event involving the short posterior ciliary arteries supplying the optic nerve head. In other words, when blood flow falters in this critical vascular network, the crowded architecture of the optic disc leaves little room for error. The resulting ischemia damages the anterior portion of the optic nerve, leading to an abrupt loss of visual field or acuity.

Although complete blindness is uncommon, the psychological impact of partial, irreversible vision loss can be substantial. Worse yet, patients who experience NAION in one eye face a higher risk of developing it in the other eye — a reality that physicians must discuss, however reluctantly, during follow-up care.

Risk factors for NAION are well documented and include:

age over 50
white race
small cup-to-disc ratio (“crowded disc”)
hypertension, diabetes, and hyperlipidemia

The “disc-at-risk,” a small scleral channel packed tightly with optic nerve fibers, remains the anatomical hallmark of susceptibility. If this compact structure experiences even modest ischemia, the resulting swelling further compromises local circulation — a vicious cycle exquisitely designed to frustrate both patients and ophthalmologists.

In addition to the classic vascular risk factors, several other conditions have been hypothesized to contribute: glaucoma, sleep apnea, arteriosclerosis, cardiac surgery, and even nocturnal hypotension. Any systemic state that reduces perfusion to the optic nerve may tip the physiological balance.

Shared Risk Factors: Why ED Patients May Appear Overrepresented

Here is where the narrative becomes clinically nuanced. Erectile dysfunction and NAION share a strikingly overlapping risk profile. Hypertension, diabetes, hyperlipidemia, and smoking — the very pillars of vascular compromise — are central to the development of both conditions.

In fact, epidemiological data demonstrate that men seeking treatment for ED behave very differently from the general male population in terms of comorbidities. For example, among more than 270,000 men with ED, the prevalence of diagnosed hypertension and diabetes in the 56–65 age group reached 51% and 23%, respectively — far higher than their prevalence in the general US adult population.

The similarity of vascular risk burdens between ED patients and NAION patients means that any overlap between sildenafil use and NAION diagnosis must be interpreted with caution. Patients receiving sildenafil are not randomly sampled from the male population; they represent a group already enriched with vascular vulnerabilities.

Thus, the mere observation that some cases of NAION occurred in individuals who had taken sildenafil does not imply causality. It reflects, instead, a far more mundane truth: the same patients who experience ED are those naturally predisposed to conditions such as NAION.

Regulatory Attention and Postmarketing Concerns

Reports linking NAION and PDE5 inhibitors began emerging after sildenafil’s approval in 1998. The Food and Drug Administration (FDA), trained to be appropriately suspicious of low-frequency but high-impact adverse events, requested updated prescribing information for all PDE5 inhibitors, including sildenafil, tadalafil, and vardenafil.

The revised labeling acknowledges the postmarketing cases of NAION temporally associated with PDE5 inhibitor use. However, the language reflects the uncertainty inherent in spontaneous reports: the events were rare, most patients had known predisposing factors, and causality could not be established.

The FDA guidance advises:

discontinuation of PDE5 inhibitors in the event of sudden vision loss
heightened caution in individuals with a prior history of NAION
careful risk–benefit discussions for patients with significant vascular risk profiles

Notably, no NAION cases were reported in sildenafil users treated for pulmonary arterial hypertension (Revatio®), suggesting that the phenomenon, if present at all, is neither universal nor mechanistically obvious.

The Challenge of Interpreting Spontaneous Case Reports

Spontaneous reporting systems — while invaluable for detecting early safety signals — carry inherent limitations. Reports may be incomplete, unverified, or influenced by media attention. They cannot establish incidence rates, much less causality. Indeed, the sudden media interest around possible “blindness from Viagra” likely encouraged patients and physicians alike to report events that might otherwise have gone undocumented.

The authors of the source study wisely note that spontaneous reporting often both underestimates and overestimates true incidence. For a rare condition such as NAION, accurate epidemiologic assessment requires structured data, controlled observation, and sufficiently large sample sizes — criteria that spontaneous report registries simply do not meet.

Population-Based Incidence of NAION: Understanding the Baseline

Two major population-based studies offer insight into the baseline incidence of NAION in the general US population.

The Rochester Epidemiology Project reported an incidence of 10.3 cases per 100,000 adults aged ≥50 years. Among men alone, the incidence was slightly higher at 11.8 per 100,000. A second, larger study using data from ophthalmologists in Missouri and Los Angeles found a much lower incidence: 2.3 cases per 100,000 adults in the same age group, and 2.52 per 100,000 among men.

After adjustments for survey nonresponse, the corrected incidence rose modestly to 3.06 cases per 100,000. Regardless of the variability, these data demonstrate that NAION is rare — a point worth repeating whenever discussions about sildenafil safety arise.

Assessing NAION Incidence in Sildenafil Users: What the Data Show

To evaluate whether sildenafil use meaningfully alters NAION risk, investigators examined data from three robust sources: global clinical trials, the International Men’s Health Study, and a large UK prescription-event monitoring study.

Clinical Trials: More Than 13,400 Men, Zero Cases

Across more than 13,300 patient-years of sildenafil exposure in clinical trials conducted between 1993 and 2003, not a single case of NAION was reported. Although clinical trials sometimes underrepresent real-world risks, the complete absence of cases provides an important signal.

The International Men’s Health Study: 2935 Patient-Years, Zero Cases

This prospective study across Germany, France, Spain, and Sweden followed more than 3800 men with ED. Detailed quarterly questionnaires and rigorous confirmation of serious events yielded no NAION cases during nearly 3000 patient-years of observation.

UK Prescription Event Monitoring Study: 35,500 Patient-Years, One Case

This large, independent epidemiologic study identified a single case of NAION among 35,500 patient-years of sildenafil use. Importantly, that patient:

was 61 years old
smoked
had hypertension and ischemic heart disease
was taking multiple medications
developed NAION more than a year after starting sildenafil

Even taken at face value, this single case translates to an incidence of 2.8 cases per 100,000 patient-years — nearly identical to background population levels.

Clinical Interpretation: Coincidence, Not Causation

When all data are viewed together, a consistent pattern emerges: the incidence of NAION among sildenafil users aligns with — and does not exceed — the incidence observed in the general population of similarly aged adults.

The reasons for this are conceptually straightforward:

Patients with ED have high baseline NAION risk due to shared vascular comorbidities.
Large datasets do not show increased incidence, despite extensive global exposure.
The pathophysiology of NAION does not align with sildenafil’s mechanism of action, and no biological model convincingly explains a causal link.
The few reported cases reflect background population risk, not drug-induced injury.

Thus, available evidence strongly suggests coincidence rather than causation.

Practical Guidance for Clinicians

Although the data do not support a causal link, clinical prudence remains essential. Physicians prescribing PDE5 inhibitors should:

review ocular history, particularly prior NAION
discuss vascular risk factor control (hypertension, diabetes, lipids)
emphasize smoking cessation
instruct patients to seek immediate attention for sudden visual symptoms

These conservative measures mirror best practices for any patient with vascular comorbidities — regardless of sildenafil use.

Conclusion

Sildenafil citrate remains a well-studied, widely used, and generally safe therapy for erectile dysfunction. Based on more than 52,000 patient-years of observation across epidemiologic studies and clinical trials, the incidence of nonarteritic anterior ischemic optic neuropathy in sildenafil users mirrors the incidence in the general population of men aged 50 years and older.

While spontaneous reports may have raised suspicion, systematic evidence does not support an increased risk of NAION attributable to sildenafil. Instead, overlapping vascular risk profiles explain the rare coincidences observed in clinical practice.

From a clinical perspective, vigilance is always appropriate — but alarm is not.

FAQ: Key Questions About Sildenafil and NAION

1. Does sildenafil directly cause NAION?

No. Current evidence does not support a causal relationship. NAION cases in sildenafil users occur at the same rate expected based on age and vascular risk factors in the general population.

2. Should patients with a history of NAION avoid PDE5 inhibitors?

Yes. Regulatory agencies advise caution and generally recommend avoiding PDE5 inhibitors in individuals who have had NAION in one eye, as these patients are at increased baseline risk for recurrence.

3. What should a patient do if vision changes suddenly after taking sildenafil?

They should stop the medication immediately and seek urgent ophthalmologic evaluation. Although causal linkage is unlikely, prompt assessment is essential to prevent further visual loss.