Fungal keratitis capsule
✍️ rare.
✍️ usually seen with trauma with organic material or where there is underlying susceptibility such as tissue devitalization or immunosuppression (including topical corticosteroid use).
✍️ Candida, Fusarium, and Aspergillus spp. are the most common infectious agents.
✅ Risk factors
✍️ trauma (including LASIK)
✍️ immunosuppression
☝️ topical corticosteroids
☝️ alcoholism
☝️ diabetes
☝️ systemic immunosuppression
✍️ ocular surface disease
☝️ dry eye
☝️neurotrophic cornea
☝️hot humid climate
☝️contamination with organic matter (agricultural work, gardening, etc.)
✅ Yeast infection
✍️ Candida species
✍️ Frequently associated with immunosuppression
✍️ those who have a compromised ocular surface
✅ Filamentary fungal infection
✍️ Fusarium and Aspergillus species.
Clinical features
✅ General
✍️ variable presentation
✍️ onset ranging from insidious to rapid
✍️ symptoms range from none to pain, photophobia, tearing, and dropped VA.
✅ Yeast infection
✍️ insidious or rapid
✍️ often localized with button appearance expanding stromal infiltrate with relatively small epithelial ulceration.
✅ Filamentary fungal infection
✍️ usually insidious.
✍️ Early
☝️ may be asymptomatic
☝️ intact epithelium
☝️ minimal corneal stromal infiltrate
☝️ mild AC in ammation.
✍️ Later
☝️ satellite lesions
☝️ feathery branching infiltrate
☝️ immune ring.
✍️ In severe infection
☝️ ulceration
☝️ involvement of deeper corneal layers and Descemet’s membrane
☝️ white plaque on the endothelium
☝️ severe AC inflammation (hypopyon).
✅ Complications
✍️ limbal and scleral extension
✍️ corneal perforation
✍️ endophthalmitis
✍️ 2ry bacterial infections (infectious crystalline keratopathy)
NB In late infection, these distinctive patterns may be lost, and the clinical appearance may resemble an advanced bacterial keratitis.
✅ Investigation
✍️Perform early and adequate corneal scrapes
✍️ Stains
☝️ gram (stains fungal walls)
☝️ giemsa (stains walls and cytoplasm)
☝️ grocott’s methenamine silver (GMS) stain, periodic acid–Schi (PAS) stain, and Calco uor white may also be used.
✍️ Culture
☝️ Sabouraud dextrose agar (for most fungi)
☝️ blood agar (for Fusarium)
✍️ If strong clinical suspicion, but negative investigations consider
☝️ confocal microscopy
☝️ corneal biopsy for histopathology
☝️ PCR for fungal DNA.
✅ Fungal keratitis treatment
✍️ Effective eradication of fungi is frequently difficult because of the deeply invasive nature of the infectious process.
✍️ Identification of the organism must be a priority so as to ensure the optimal choice of therapy.
✍️ Admit.
✍️ Intensive topical broad-spectrum antifungal agents
☝️ non-preserved clotrimazole 1%
☝️ natamycin 5% (preserved only)
☝️ voriconazole 1%
☝️ dose hourly day and night for the first 72h
☝️ voriconazole is the preferred agent for suspected or proven candidal infection and natamycin for filamentary fungal infection.
☝️ For severe or unresponsive disease, add a second agent (preservative-free amphotericin 0.15% hourly day and night for first 24h, then reducing to day only).
☝️ Avoid corticosteroids (reduce or stop them if already on them) but may cautiously be used during healing phase
☝️ Oral analgesia and cycloplegia (preservative-free cyclopentolate 1% 3×/d).
✍️ Systemic treatment in fungal keratitis
☝️ consider oral fluconazole (50–100mg 1×/d for 7–14d) which is effective against Candida and Aspergillus.
☝️ In resistant cases or where Aspergillus has been identified: consider voriconazole (PO 400mg 2×/d for two doses, then 200mg 2×/d, but can increase to 300mg 2×/d OR (IV 6mg/kg 2×/d for two doses, then 4mg/kg 2×/d).
☝️ An alternative for invasive yeast infections is IV flucytosine (50mg/kg 4×/d then adjust as per plasma level monitored
☝️ Consider systemic antifungal treatment with
• Severe disease
• deep stromal lesions
• threatened perforation
• endophthalmitis
• All immunocompromised patients.
• Topical treatment should be continued.
☝️ Liaise with a microbiologist for advice drug selection, dosing, and monitoring.
☝️ Systemic antifungals are associated with significant side effects
• renal dysfunction (voriconazole)
• hepatotoxicity ( fluconazole, voriconazole)
• blood disorders ( flucytosine, voriconazole).
☝️ Monitoring should include FBC, U+E, and LFT prior to starting treatment and at least weekly during treatment.
☝️ dosing may need to be reduced in the presence of renal dysfunction
✍️ Taper treatment, according to clinical improvement.
✍️ Relapse is common and may signify incomplete sterilization or reactivation.
✍️ Treatment is prolonged (12wk).
✍️ In the healing phase, topical corticosteroids (preservative-free dexamethasone 0.1% 1×/d) are sometimes used but this should be at the direction of a corneal specialist and carefully monitored.
✍️ Consider PK
☝️ progressive disease (to remove fungus or prevent perforation)
☝️ in the quiet, but visually compromised, eye.
Antifungal agents and mode of action
✍️ Polyene
☝️Destabilize cell wall
☝️ Natamycin, amphotericin
✍️ Imidazole
☝️ Destabilize cell wall
☝️ Clotrimazole, econazole, ketoconazole, miconazole
✍️ Triazole
☝️ Destabilize cell wall
☝️ Itraconazole, voriconazole, fluconazole
✍️ Pyrimidine
☝️ Cytotoxic
☝️ Flucytosine