What is the association between Phosphodiesterase-5 (PDE-5) inhibitors and the risk of Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION)?

PDE-5 Inhibitors and NAION Risk

PDE-5 inhibitors are associated with an approximately twofold increased risk of non-arteritic anterior ischemic optic neuropathy (NAION), with a relative risk of 1.34 (CI, 1.17 to 1.55) for "possible NAION" and should be absolutely avoided in patients with a history of NAION in either eye. 1

Risk Assessment and Relationship

PDE-5 inhibitors have been linked to NAION through several mechanisms:

• Case-crossover studies show approximately twofold increased risk of acute NAION within five half-lives of PDE-5 inhibitor use 2
• The absolute risk is relatively small but significant:
  • 4.6 cases per 10,000 men per year for definite NAION
  • 2.4 cases per 10,000 men per year for possible NAION 3

The relationship appears to be temporal, with NAION occurring between 30 minutes and 36 hours after medication intake 4. This timing corresponds with the pharmacological activity period of these medications.

Risk Factors and Patient Selection

Patients at highest risk for developing NAION while using PDE-5 inhibitors include those with:

• Structurally predisposed optic discs ("crowded disc") 1, 5, 6
• Age over 50 years 6
• Vascular risk factors:
  • Diabetes
  • Hypertension
  • Hyperlipidemia
  • Coronary artery disease
  • Smoking 6

Clinical Recommendations

Contraindications

• Previous history of NAION in either eye is a strong contraindication for PDE-5 inhibitor use 1, 5, 6
• Multiple case reports document sequential NAION in the contralateral eye when patients continued PDE-5 inhibitor use after an initial NAION event 7

Patient Counseling

Before prescribing PDE-5 inhibitors:

1. Assess for pre-existing optic nerve disorders
2. Document baseline visual acuity and visual fields
3. Evaluate for vascular risk factors 1
4. Inform patients about the small but present risk of this vision-threatening condition

Monitoring and Management

• Advise patients to seek immediate medical attention for any visual disturbances 5, 6
• Instruct patients to stop taking PDE-5 inhibitors immediately if visual changes occur 5, 6
• If NAION is diagnosed, discontinue PDE-5 inhibitor use permanently 8

Pathophysiology and Mechanism

The mechanism linking PDE-5 inhibitors to NAION likely involves:

• Vasodilatory properties affecting optic nerve head blood flow
• Possible nocturnal hypotension exacerbated by PDE-5 inhibitors
• Compromised blood flow through posterior ciliary arteries in predisposed individuals 1

Important Caveats

1. The shared risk factors between erectile dysfunction and NAION make causality assessment challenging
2. FDA and drug manufacturers have updated product labeling to reflect this risk 5, 6
3. Unfortunately, no proven effective treatment exists for NAION once it occurs 1
4. Visual recovery is generally limited, with only about 40% of patients experiencing some spontaneous improvement 1

In summary, while the absolute risk is small, the potential for permanent vision loss makes this a serious consideration when prescribing PDE-5 inhibitors, particularly in patients with pre-existing risk factors or a history of NAION.