What is the treatment for a fungal corneal ulcer with hypopyon?

Treatment of Fungal Corneal Ulcer with Hypopyon

Initiate topical natamycin 5% (NATACYN®) one drop hourly or every two hours as first-line therapy for fungal keratitis with hypopyon, and obtain corneal scrapings for culture and sensitivity testing before starting treatment to guide subsequent therapy. 1

Immediate Management Algorithm

Initial Diagnostic Steps

• Obtain corneal scrapings immediately using proparacaine 0.5% anesthetic (avoid tetracaine due to antimicrobial effects) from the base and periphery of the ulcer before initiating antifungal therapy 2, 3
• Inoculate samples directly onto fungal culture media (Sabouraud agar) and perform KOH/Calcofluor white staining to visualize fungal elements 2
• Do NOT tap the hypopyon - it is typically sterile in fungal keratitis unless there is concurrent endophthalmitis from trauma or surgery 2

First-Line Antifungal Therapy

Natamycin 5% is the only FDA-approved topical antifungal for fungal keratitis and should be started immediately 1:

• Loading phase: 1 drop hourly or every 2 hours for the first 3-4 days 1
• Maintenance phase: Reduce to 1 drop 6-8 times daily after initial improvement 1
• Duration: Continue for 14-21 days or until complete resolution of active infection 1
• Gradual taper: Reduce dosage at 4-7 day intervals to ensure organism elimination 1

Alternative and Adjunctive Antifungal Options

If natamycin fails or for specific organisms, consider these alternatives based on culture results:

• Voriconazole shows the lowest minimum inhibitory concentration (MIC) against most fungal pathogens and may be superior to natamycin, particularly for Aspergillus species 4, 5
• Amphotericin B 0.15-0.3% topical ointment or drops can be compounded for resistant cases, especially Aspergillus fumigatus and Fusarium solani 6
• Intracameral amphotericin B (5-10 μg/0.1 mL sterile water) or voriconazole (100 μg/0.1 mL) may be necessary for severe cases with deep stromal involvement 2, 5

Critical Management Considerations

Organism-Specific Treatment Adjustments

• Aspergillus species: Higher natamycin MIC values warrant early consideration of voriconazole or amphotericin B 4
• Fusarium species: Natamycin is FDA-approved specifically for Fusarium solani keratitis 1
• Candida species: May present with ring infiltrates and hypopyon; consider fluconazole 400-800 mg daily orally for susceptible isolates 2, 7

Adjunctive Medical Therapy

• Cycloplegics (atropine 1% or homatropine 5%) to reduce pain and prevent synechiae formation 3
• Oral doxycycline or minocycline (100 mg twice daily) to inhibit matrix metalloproteinases and reduce corneal melting risk 2
• AVOID topical corticosteroids initially - fungal keratitis has worse outcomes than bacterial keratitis with higher perforation rates 2
• Steroids may be considered cautiously only after definitive fungal identification, confirmed response to antifungals, and ruling out Nocardia 3, 5

Surgical Interventions for Complicated Cases

Indications for Surgical Management

Consider surgical intervention when:

• Progressive stromal thinning despite maximal medical therapy 2
• Impending or frank corneal perforation 2
• Large corneal perforation requiring structural support 2
• Unresponsive disease after 7-10 days of appropriate antifungal therapy 2

Surgical Options

• Amniotic membrane transplantation: May stabilize the ocular surface and improve outcomes, though it does not reduce hypopyon size or duration 2
• Therapeutic penetrating keratoplasty: For large perforations or progressive disease; send excised tissue for pathology and culture 2
• Tissue adhesive with bandage contact lens: For small perforations with good surrounding tissue 2
• Tenon's patch graft with cyanoacrylate glue: Effective for larger perforations 2

Monitoring and Follow-Up Protocol

• Daily examination initially until clear clinical improvement is documented 3
• Reassess at 3-4 days: If no improvement, reculture after stopping antifungals for 12-24 hours 2
• Expect slower healing: Fungal keratitis has slower re-epithelialization and higher perforation rates compared to bacterial keratitis 2
• Continue treatment for minimum 14-21 days even with clinical improvement to prevent relapse 1

Common Pitfalls to Avoid

• Do not delay corneal scraping - clinical differentiation between bacterial and fungal keratitis is correct in less than 70% of cases by experienced cornea specialists 2
• Do not use preserved anesthetics or cycloplegics before obtaining cultures as they reduce culture yield 2
• Do not start corticosteroids early - this is particularly dangerous in fungal keratitis and can lead to rapid progression 3, 5
• Do not assume natamycin will work for all fungi - Aspergillus species may require voriconazole or amphotericin B from the outset 4
• Do not stop treatment too early - gradual taper over 4-7 day intervals is essential to prevent recurrence 1

Fungal keratitis with hypopyon represents a sight-threatening emergency requiring aggressive initial therapy, close monitoring, and low threshold for surgical intervention given the higher perforation rates and worse visual outcomes compared to bacterial keratitis. 2