What are the considerations for prescribing phosphodiesterase-5 (PDE-5) inhibitors in patients with a history of nonarteritic anterior ischemic optic neuropathy (NAION)?

PDE-5 Inhibitors and Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)

PDE-5 inhibitors should be avoided in patients with a history of NAION in either eye due to increased risk of recurrence, and patients without prior NAION should be counseled about the small but significant increased risk of developing this vision-threatening condition.

Risk Assessment and Association

PDE-5 inhibitors have been associated with an increased risk of developing NAION, though the evidence is of varying quality:

• Very-low-quality evidence from a large study of 4 million veterans aged 50 years or older showed that while PDE-5 inhibitors were not associated with an increased risk for definite NAION (relative risk 1.02), they were associated with an increased risk for "possible NAION" with a relative risk of 1.34 [CI, 1.17 to 1.55] and an absolute risk of 2.4 cases per 10,000 men per year 1

• A case-crossover study found an approximately twofold increased risk of acute NAION within five half-lives of PDE-5 inhibitor use (OR 2.15,95% CI: 1.06-4.34) 2

• Based on these findings, it's estimated that weekly use of PDE-5 inhibitors adds approximately three NAION cases per 100,000 men 50 years and older annually 2

Contraindications and Precautions

The FDA drug labels for PDE-5 inhibitors contain specific warnings regarding NAION:

1. Absolute contraindication:

   • Individuals who have already experienced NAION in one eye are at increased risk of NAION recurrence and should avoid PDE-5 inhibitors 3, 4, 5

2. Relative contraindications/use with caution:

   • Patients with "crowded" optic disc (small cup-to-disc ratio)
   • Age over 50
   • Vascular risk factors (diabetes, hypertension, coronary artery disease, hyperlipidemia)
   • Smoking 3, 4

Patient Counseling and Monitoring

When prescribing PDE-5 inhibitors to patients without prior NAION:

1. Pre-treatment assessment:

   • Evaluate for pre-existing optic nerve disorders
   • Document baseline visual acuity and visual fields
   • Assess for vascular risk factors (diabetes, hypertension, etc.) 5

2. Patient education:

   • Advise patients to stop the medication and seek immediate medical attention for any sudden vision changes
   • Explain that visual symptoms can occur even hours after medication intake 5, 3
   • Inform that the risk is small but present (approximately 2.4 cases per 10,000 men per year) 1

3. Monitoring:

   • Regular follow-up for patients with risk factors for NAION
   • Consider ophthalmology referral for patients with multiple risk factors

Clinical Presentation and Timing

NAION associated with PDE-5 inhibitors can occur:

• Within the expected duration of drug action
• Even up to 36 hours after intake when blood levels are minimal 6
• May affect one or both eyes
• Presents as sudden, painless vision loss, often noticed upon awakening

Alternative Treatments for Erectile Dysfunction

For patients with a history of NAION or multiple risk factors who should avoid PDE-5 inhibitors:

1. Consider vacuum erection devices (VEDs) as an alternative treatment option 1
2. Explore non-PDE-5 inhibitor approaches as recommended by the Princeton Consensus Panel 1
3. Address modifiable risk factors such as hypertension, diabetes, and sleep apnea 5

Risk Mitigation Strategies

For patients at risk but requiring treatment:

• Consider taking antihypertensive medications in the morning rather than at night to avoid nocturnal hypotension 5
• Treat sleep apnea if present 5
• Manage vascular risk factors aggressively

Conclusion

The relationship between PDE-5 inhibitors and NAION remains under investigation, but current evidence suggests a small but significant increased risk. While the absolute risk is low, the potential for permanent vision loss warrants careful patient selection, thorough counseling, and appropriate monitoring when prescribing these medications.