A 68-year-old woman with poorly controlled diabetes mellitus (HbA1c 9.2%) presents with a 10-day history of progressive left eye pain, blurred vision, and a white corneal infiltrate. She recalls a minor eye trauma from a plant thorn 3 weeks prior. On slit-lamp examination, the ulcer has a dry, granular, feathery appearance with minimal hypopyon. KOH mount of corneal scrapings reveals septate hyphae. Bacterial culture remains sterile after 48 hours. What is the most appropriate next step in management?

Explanation

## Clinical Diagnosis: Fungal Corneal Ulcer **Key Point:** The combination of: - Organic matter injury (plant thorn) - Dry, granular, feathery ulcer morphology - **Septate hyphae on KOH mount** (diagnostic) - Sterile bacterial culture - Poorly controlled diabetes (immunosuppression) ...confirms a **fungal corneal ulcer**, most likely *Aspergillus* or *Fusarium* species. **High-Yield:** Septate hyphae = filamentous fungus (Aspergillus, Fusarium). Sterile bacterial culture + KOH positivity = fungal keratitis. Plant trauma + diabetes = classic risk factors. ## Management Protocol ### First-Line Antifungal Therapy **Topical natamycin 5%** is the gold standard for fungal corneal ulcers [cite:Kanski 9e Ch 4]. | Agent | Spectrum | Dosing | Corneal Penetration | Notes | |-------|----------|--------|---------------------|-------| | **Natamycin 5%** | Filamentous fungi (Aspergillus, Fusarium) | Every 1 hour | Good | First-line for fungal keratitis | | Itraconazole 200 mg | Systemic antifungal | BD | Excellent (oral) | Adjunctive to topical therapy | | Fluconazole 400 mg | Candida, some Aspergillus | Daily | Moderate | Less effective for Aspergillus/Fusarium | | Amphotericin B 0.15% | Broad antifungal | Every 1 hour | Poor | Toxic to cornea; reserved for severe/refractory cases | | Voriconazole | Broad spectrum | Variable | Excellent (oral) | Expensive; reserved for resistant/severe disease | **Clinical Pearl:** Natamycin is a **polyene antibiotic** with excellent activity against filamentous fungi and good corneal penetration. It does not penetrate the anterior chamber well, so systemic antifungal (itraconazole) is essential for adjunctive coverage. ### Dosing Regimen 1. **Topical natamycin 5%** every 1 hour while awake (16 hours/day) for the first 2 weeks 2. **Oral itraconazole 200 mg BD** for systemic coverage (better corneal penetration than fluconazole for Aspergillus) 3. **Cycloplegic agent** (tropicamide 1%) TID to reduce pain 4. **Lubricating drops** (preservative-free) QID 5. **Optimize glycemic control** (HbA1c 9.2% is suboptimal)—insulin or intensified oral agents **Warning:** Do NOT use topical corticosteroids in fungal keratitis; they promote fungal proliferation and perforation. ### Monitoring - Daily slit-lamp examination for ulcer size, infiltration, and feathery border progression - Reduce natamycin frequency to every 2 hours after 2 weeks if ulcer shows improvement - Repeat KOH mount or culture if no improvement in 3–4 weeks - Consider corneal biopsy only if diagnosis is uncertain or treatment fails **High-Yield:** Fungal ulcers progress slowly (weeks) and respond slowly to therapy (2–4 weeks). Bacterial ulcers progress rapidly (days) and respond quickly (3–5 days). ## Why Itraconazole Over Fluconazole? Itraconazole has superior activity against *Aspergillus* and *Fusarium* species compared to fluconazole, which is more effective against *Candida*. Given the KOH-positive septate hyphae (filamentous fungi), itraconazole is preferred [cite:Aravind Eye Care System]. ## Glycemic Control Diabetes impairs corneal healing and immune response. Optimization of HbA1c is essential to prevent recurrence and promote ulcer healing.