Treatment of Choice for Active Ocular Histoplasmosis
For active ocular histoplasmosis, anti-vascular endothelial growth factor (anti-VEGF) therapy is the treatment of choice for choroidal neovascularization, while systemic antifungal therapy with itraconazole is recommended for disseminated or active histoplasmosis infection. 1, 2
Understanding Ocular Histoplasmosis Syndrome (OHS)
Ocular histoplasmosis syndrome is characterized by:
- Punched-out atrophic chorioretinal lesions ("histo spots")
- Peripapillary scarring
- Absence of vitreal inflammation
- Choroidal neovascularization (CNV) - the primary cause of vision loss 2
Treatment Algorithm
1. For Active Choroidal Neovascularization in OHS:
Location-based treatment approach:
Subfoveal and juxtafoveal CNV:
- First-line: Anti-VEGF therapy 2
- Alternative: Photodynamic therapy or combination therapy
Extrafoveal CNV:
2. For Systemic/Disseminated Histoplasmosis with Ocular Involvement:
Initial therapy:
- Liposomal amphotericin B (3-5 mg/kg IV daily) for 1-2 weeks 1
Step-down therapy:
- Itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily 1
- Total treatment duration: at least 12 weeks 1
- Monitor blood levels of itraconazole after 2 weeks to ensure adequate drug exposure 1
Important Clinical Considerations
Monitoring and Follow-up
- Regular monitoring with spectral-domain optical coherence tomography to assess disease activity and CNV regression 2
- Self-monitoring with Amsler grid for early detection of CNV 4
- For patients on systemic antifungals:
- Monitor renal function, electrolytes, CBC, and liver function tests during amphotericin B therapy
- Check itraconazole blood levels to ensure therapeutic concentrations 1
Cautions and Contraindications
- Avoid voriconazole as it has been associated with increased mortality in the first 42 days compared to itraconazole in histoplasmosis treatment 5
- Fluconazole has lower success rates than itraconazole and may lead to resistance 1
- Patients with OHS considering LASIK surgery should be informed that the procedure may trigger choroidal neovascularization 4
Prevention of Reactivation
- Aggressive treatment of other fungal infections (dermatomycoses, onychomycosis, vaginal candidiasis) may decrease risk of OHS lesion reactivation 4
- Patients should be educated on avoiding activities that create dust in endemic areas, especially those with compromised immunity 6
Special Populations
Immunocompromised patients:
- May require longer or indefinite suppressive therapy with itraconazole 200 mg daily 6
- More aggressive monitoring for disease progression
Pregnant women:
- Amphotericin B formulations are preferred due to teratogenicity of azoles 6
Emerging Therapies
- Submacular surgery for removal of subfoveal CNV shows promising results in selected cases 3
- Antiangiogenic compounds being developed for age-related macular degeneration may benefit OHS-associated CNV 3
The management of ocular histoplasmosis requires close collaboration between ophthalmologists and infectious disease specialists to address both the ocular manifestations and any underlying systemic infection.