What is the management of fungal keratitis?

Management of Fungal Keratitis

Topical natamycin 5% applied hourly or every 2 hours is the first-line treatment for fungal keratitis, with frequency reduced to 6-8 times daily after 3-4 days and continued for 14-21 days until resolution. 1

Initial Diagnostic Approach

Before initiating therapy, obtain corneal scrapings for:

• KOH staining and Gram stain to identify fungal elements 2
• Fungal culture to determine the specific organism and guide therapy 2, 1
• In vitro susceptibility testing when possible to optimize antifungal selection 1

Clinical features suggesting fungal rather than bacterial keratitis include:

• Dry rather than suppurative appearance 2
• Feathered edges of the infiltrate 2
• Satellite lesions 2
• Posterior endothelial plaque 2
• Ring infiltrate (also seen in Acanthamoeba) 2

Stepwise Treatment Algorithm (TST Protocol)

Step 1: Topical Monotherapy

Start with topical natamycin 5%:

• Initial dosing: 1 drop hourly or every 2 hours 1
• Reduce to 6-8 times daily after 3-4 days 1
• Continue for 14-21 days or until resolution 1
• Gradually taper dosage at 4-7 day intervals to ensure organism elimination 1

Step 2: Add Systemic Therapy

Add oral antifungals if:

• Ulcer size >5 mm 3
• Depth >50% of corneal thickness 3
• Impending perforation 3

Systemic options:

• Oral voriconazole (preferred for Aspergillus and severe cases) 2, 3
• Oral ketoconazole 3

Step 3: Targeted Topical Therapy

If poor response at 7-10 days, add:

• Topical voriconazole 1% 1, 3
• Alternative topical agents: chlorhexidine, amphotericin B, or econazole 4

Critical caveat: Failure to improve after 7-10 days suggests the organism may not be susceptible to natamycin and requires reassessment 1

Step 4: Intrastromal/Intracameral Injections

For severe cases not responding to combination topical and systemic therapy:

• Intrastromal antifungal injections achieve steady-state drug levels within corneal tissue 5
• Intracameral injections for deep stromal infiltration 2, 5, 3
• Voriconazole can be administered intravitreally or systemically for endophthalmitis 2

Step 5: Surgical Intervention

Therapeutic penetrating keratoplasty (PKP) is indicated for:

• Corneal perforation 6, 3
• Progressive disease despite maximal medical therapy 6, 3
• Severe cases with impending perforation 3

Surgical outcomes:

• 79.6% graft clarity rate with no recurrence when infection completely removed 6
• Early surgical intervention before advanced disease is critical 6
• Complete removal of infected tissue is essential for cure 6

Adjunctive Management

Cycloplegic agents:

• Use when substantial anterior chamber inflammation present 2
• Decreases pain and prevents synechia formation 2

Corticosteroid use - AVOID in fungal keratitis:

• Corticosteroids are a risk factor for requiring penetrating keratoplasty 2
• Should be avoided in fungal, Acanthamoeba, and Nocardia infections 2
• If patient already on steroids at presentation, reduce or eliminate until infection controlled 2

Post-surgical antifungal therapy:

• Continue antifungal therapy for 1-2 months post-keratoplasty with gradual tapering 6
• Cyclosporine for rejection prevention starting 2 weeks post-PKP 6
• Topical steroids only for grafts >8.5 mm with heavy iris inflammation, starting 2 weeks post-PKP 6

Organism-Specific Considerations

Fusarium (most common, 42.2%):

• Responds to natamycin monotherapy 3
• May require combination therapy for severe cases 3

Aspergillus (32.8%):

• Voriconazole preferred systemically 2, 3
• Amphotericin B historically recommended 2

Candida:

• May present as mixed infection 7
• Responds to standard natamycin therapy 6

Expected Outcomes with TST Protocol

• Treatment success rate: 79.8% 3
• Mean healing time: 41.5 ± 22.2 days 3
• Corneal perforation rate: 7% 3
• Keratoplasty required: 20.2% 3
• Visual acuity improvement: from 2.05 logMAR at presentation to 1.6 logMAR at 3 months 3

Critical Pitfalls to Avoid

• Do not delay treatment while awaiting culture results in clinically suspected fungal keratitis 1, 5
• Do not use corticosteroids during active fungal infection 2
• Do not continue ineffective therapy beyond 7-10 days without reassessment 1
• Do not perform partial debridement during keratoplasty—complete removal of infected tissue is essential 6
• Do not confuse pooling of fluorescein stain in areas of thinning with true epithelial defects 2