Fungal Keratitis

Fungal keratitis is a corneal infection by filamentous fungi (Fusarium, Aspergillus, Curvularia) or yeasts (Candida). It has a more indolent, but often more destructive, course than bacterial disease because antifungal penetration is poor.

• Filamentous keratitis follows trauma with vegetable matter or soil (agricultural workers, particularly in warm and humid regions); Candida affects eyes with a compromised surface (chronic keratitis, topical steroid use, dry eye, corneal graft, diabetes).
• Prevalence is high in tropical and subtropical regions. Prior topical corticosteroid therapy is a risk for severity.

• Gradual onset of pain, redness, photophobia, and reduced vision over days; symptoms may be less intense than bacterial infection initially.
• Dry, raised, rough or feathery grey white infiltrate with irregular edges, satellite lesions, an immune ring, hyphate extension into deep stroma, and an endothelial plaque.
• Hypopyon is common in advanced cases and may be thick and sterile or contain fungi.
• Candida produces a dense yellow white infiltrate with an overlying epithelial defect, like bacterial ulcers.
• Rapid melting and perforation can follow if there is deep stromal involvement.

• Corneal scraping with a spatula or blade from the base and edges: 10 percent potassium hydroxide wet mount or calcofluor white for hyphae, Gram and Giemsa stains; culture on Sabouraud dextrose agar (no cycloheximide) and blood agar; results in 2 to 7 days and sometimes longer.
• In vivo confocal microscopy shows hyphae and is non-invasive.
• PCR for fungal DNA.
• Anterior segment OCT to measure depth.
• Corneal biopsy if scraping is negative and clinical suspicion is high.
• B-scan for endophthalmitis in cases with hypopyon or opaque media.

• Stop topical corticosteroids at once.
• Topical antifungal therapy:
  • Natamycin 5 percent suspension: 1 drop hourly while awake (or every 1 to 2 hours) for the first 1 to 2 weeks, then every 2 to 4 hours until the epithelium heals and infiltrate resolves (total typically 3 to 6 weeks). It is the first choice for filamentous disease, particularly Fusarium.
  • Voriconazole 1 percent: 1 drop hourly, effective against Aspergillus and Candida; can be combined with natamycin in severe disease.
  • Amphotericin B 0.15 percent hourly for Candida or when other drugs fail.
  • Fluconazole 0.2 percent drops for Candida.
• Systemic antifungal therapy for deep stromal disease, scleral extension, or endophthalmitis: oral voriconazole 400 mg twice daily for 24 hours then 200 mg twice daily (weight adjusted), or oral fluconazole 200 mg to 400 mg daily for Candida; monitor liver function.
• Intrastromal injection of voriconazole 50 micrograms in 0.1 mL (or amphotericin B 5 to 10 micrograms) around deep lesions, and intracameral voriconazole or amphotericin B for endothelial plaque or hypopyon, are used in refractory cases.
• Supportive: cycloplegia (atropine 1 percent daily), epithelial debridement every few days to improve penetration (in some protocols), oral analgesia, lubricants, and treat raised pressure.
• Oral doxycycline 100 mg twice daily if melt is present.
• Adjuncts: corneal cross linking with riboflavin and UVA (limited evidence).
• Therapeutic keratoplasty (penetrating, with a wide margin) for perforation, progression to the limbus, or no response after 10 to 14 days of maximal treatment; endophthalmitis requires vitrectomy and intravitreal voriconazole 100 micrograms in 0.1 mL or amphotericin B 5 micrograms.
• Follow up daily to every few days at first, then weekly; clinical response is slow, and relapse can occur on reduction of therapy.
• Complications: perforation, endophthalmitis, scarring, glaucoma, and loss of the eye.