What are the recommendations for eye screenings to monitor for ethambutol (antitubercular medication) toxicity in an infant?

Eye Screening for Ethambutol Toxicity in Infants

For infants receiving ethambutol, monthly color vision testing should be performed throughout treatment, with baseline and ongoing monitoring using visual-evoked potentials (VEPs) when available, as standard visual acuity testing is not feasible in this age group. 1, 2

Monitoring Schedule for Infants

Baseline Assessment (Before Starting Ethambutol)

• Visual-evoked potentials (VEPs) if specialized equipment and expertise are available 2
• Document baseline visual behavior and parental observations 2
• Note: Standard Snellen chart testing and Ishihara color plates cannot be performed in infants who cannot cooperate (typically under 5 years of age) 1

During Treatment Monitoring

• Monthly color vision testing throughout the entire duration of ethambutol therapy 1
• VEP monitoring at baseline, months 1,2,4, and 6 if available, as this can detect subclinical changes before clinical symptoms appear 2, 3
• Retinal nerve fiber layer optical coherence tomography (RNFL OCT) can detect early toxicity (increased RNFL thickness at 5 months) before visual symptoms develop 3
• Careful parental education about observing for behavioral changes suggesting visual impairment (reaching for objects, tracking movements, unusual eye movements) 2, 4

Critical Safety Considerations

Why Infants Are High-Risk

• Visual impairment is likely severely underestimated in children under 5 years because they cannot report visual symptoms 2
• The British Thoracic Society explicitly states ethambutol should only be used in patients who can appreciate and report visual symptoms, highlighting the inherent risk in infants 2
• Despite this risk, ethambutol may be necessary when drug-resistant tuberculosis is suspected 2, 5

Dosing Requirements

• Never exceed 15-20 mg/kg/day in infants 2, 4
• Careful dose calculation is essential, as toxicity is dose-dependent 1, 6
• At the recommended 15 mg/kg/day dose, ocular toxicity in children is extremely rare (0.05% or 2 out of 3,811 children) 1, 6

Practical Monitoring Algorithm

Monthly Visits Should Include:

1. Parental questionnaire about any behavioral changes suggesting vision problems 4
2. Color vision testing (documented monthly per guidelines) 1
3. VEP testing if available at months 1,2,4, and 6 2, 3
4. Clinical assessment for signs of visual disturbance 1

Post-Treatment Monitoring

• Continue monitoring for 12 months after stopping ethambutol, as early subclinical changes may progress for 6 months before returning to baseline 3
• VEP and RNFL OCT changes can persist for 6 months after discontinuation before resolving 3

When to Stop Ethambutol Immediately

• Any parental report of suspected visual changes in the infant 4
• Abnormal VEP findings showing delayed P100 latency 3
• Increased RNFL thickness on OCT suggesting early toxicity 3
• Any clinical suspicion of visual impairment, even without objective confirmation 2, 4

Key Pitfalls to Avoid

• Do not rely solely on clinical observation in infants—objective testing with VEPs is critical when available 2, 3
• Do not assume safety based on dose alone; individual susceptibility varies 4
• Do not discontinue monitoring immediately after stopping ethambutol; continue for 12 months 3
• Do not use ethambutol unless drug resistance is suspected or confirmed, given the monitoring challenges in infants 2, 5

The American College of Chest Physicians emphasizes that ethambutol toxicity can result in permanent blindness, making vigilant monitoring essential despite the practical challenges in infants 2. The FDA label confirms that visual changes may be irreversible if not recognized promptly 4.