What is the treatment of choice for active ocular histoplasmosis?

Treatment of Choice for Active Ocular Histoplasmosis

For active ocular histoplasmosis with choroidal neovascularization, anti-vascular endothelial growth factor (anti-VEGF) therapy is the treatment of choice, with systemic antifungal therapy using itraconazole recommended when there is evidence of active histoplasmosis infection. 1, 2

Antifungal Treatment Options

First-line Antifungal Therapy

• Itraconazole: 200 mg three times daily for 3 days, then 200 mg twice daily
  • Duration: At least 12 weeks for acute infection 2
  • Monitoring: Blood levels should be obtained after 2 weeks to ensure adequate drug exposure 2
  • Preferred over other azoles due to superior efficacy 2, 3

Alternative Antifungal Options (for severe cases or itraconazole intolerance)

• Liposomal amphotericin B: 3-5 mg/kg daily IV for 1-2 weeks, followed by step-down to itraconazole 2

  • Particularly indicated for severe or disseminated disease
  • Requires monitoring of renal function, electrolytes, and infusion reactions

• Fluconazole: Can be used if itraconazole is not tolerated, but has lower success rate 2

  • Not recommended as first-line due to lower efficacy and risk of resistance development

• Avoid voriconazole: Associated with increased mortality in the first 42 days compared to itraconazole (HR 4.30,95% CI 1.3-13.9) 3

Management of Ocular Manifestations

Choroidal Neovascularization (CNV) Treatment

• Location-based approach:
  • Extrafoveal CNV: Laser photocoagulation is effective 1, 4
  • Subfoveal and juxtafoveal CNV: Anti-VEGF therapy is the standard of care 1
  • Alternative/adjunctive options: Photodynamic therapy or combination therapy 1, 4

Monitoring and Follow-up

• Regular fundoscopic examinations to assess for disease progression
• Spectral-domain optical coherence tomography to monitor CNV regression 1
• Patient self-monitoring with Amsler grid to detect early symptoms of CNV 5

Prevention of Reactivation

• Aggressive treatment of concurrent fungal infections (dermatomycoses, onychomycosis, vaginal candidiasis) may decrease risk of ocular lesion reactivation 5
• Patients should avoid activities that create dust in endemic areas or disturb areas contaminated with bird/bat droppings 6
• Patients considering LASIK surgery should be informed of potential risk for triggering CNV 5

Clinical Pearls and Pitfalls

• Pitfall: Failing to recognize the distinction between treating the infectious component (with antifungals) and treating the inflammatory/neovascular complications (with anti-VEGF or laser)
• Pitfall: Using voriconazole as first-line therapy despite evidence of increased mortality compared to itraconazole
• Pearl: The absence of vitreal inflammation is characteristic of ocular histoplasmosis syndrome 7
• Pearl: Modern imaging technologies like spectral-domain OCT have improved diagnostic abilities and monitoring of disease activity 1

Special Considerations

• In pregnant women, amphotericin B formulations are preferred due to teratogenicity of azoles 6
• For severe cases with respiratory complications, adjunctive corticosteroids may be beneficial 2
• Immunocompromised patients may require longer or indefinite suppressive therapy 6