What are the indications for intrastromal antifungal (IAF) injections in patients with fungal keratitis?

Indications for Intrastromal Antifungal Injection in Fungal Keratitis

Intrastromal antifungal injection should be reserved for deep stromal fungal keratitis that has failed to respond to intensive topical and systemic antifungal therapy for at least 7-14 days. 1

Primary Indications

Deep stromal involvement with recalcitrant disease is the key indication for intrastromal antifungal injection:

• Deep stromal fungal infiltrates not responding to topical therapy represent the primary indication, as superficial anterior stromal disease should not receive intrastromal injection 1, 2
• Recalcitrant fungal keratitis defined as no improvement or progression despite combined topical voriconazole and amphotericin B hourly for at least 10 days 3
• Progressive disease despite maximal medical therapy with topical and systemic antifungals for a minimum of 7-14 days 1, 4

Clinical Scenarios Supporting Use

The following clinical presentations warrant consideration of intrastromal injection:

• Large deep stromal abscesses with satellite lesions not responding to conventional therapy 4, 5
• Aspergillus or Fusarium keratitis with deep stromal involvement, as these organisms are particularly difficult to treat with topical therapy alone 4, 3
• Acremonium keratitis unresponsive to full medical therapy over 3 weeks, where intrastromal injection has shown efficacy 6
• Cases approaching the need for therapeutic keratoplasty where medical salvage is still possible 4, 2

Absolute Contraindications

Do not proceed with intrastromal injection in the following situations:

• Impending or frank corneal perforation - these cases require immediate surgical intervention, not injection therapy 7, 1
• Extremely thin cornea (less than approximately 200 microns) where needle insertion risks iatrogenic perforation 7
• Active corneal melting with significant stromal loss making injection technically unsafe 7
• Superficial anterior stromal disease only - topical therapy is sufficient for these cases 1

Practical Decision Algorithm

Step 1: Assess disease depth and severity

• Confirm deep stromal involvement on slit-lamp examination 2
• Document failure of intensive topical therapy (hourly voriconazole and/or amphotericin B) for minimum 7-14 days 1, 3

Step 2: Evaluate corneal structural integrity

• Measure corneal thickness and assess for thinning or melting 7
• Rule out impending perforation - if present, proceed directly to surgical intervention 7, 1

Step 3: Confirm adequate trial of conventional therapy

• Verify patient has received both topical and systemic antifungals 4, 5
• Ensure compliance with hourly topical therapy before escalating to injection 3

Step 4: Proceed with injection if criteria met

• Inject voriconazole 50 μg in 0.1 ml circumferentially around the infiltrate using 30-gauge needle in five quadrants to form a barrage 4, 2
• Continue all topical and systemic antifungal therapy during injection treatment 4, 3
• Repeat injections may be necessary (mean 9.3 injections in one series) until resolution 3

Important Clinical Caveats

Fungal keratitis has inherently worse outcomes than bacterial keratitis with larger infiltrates, slower re-epithelialization, and higher perforation rates at 3 months 7, 8

The risk-benefit calculation is critical: perforation during or after injection must be weighed against progressive disease without intervention, and cases with impending perforation within hours to days should proceed directly to surgery 7

Combination intrastromal therapy with both voriconazole and amphotericin B may be more effective than single-agent injection for persistent disease, achieving resolution in 87.5% of cases 3

Expected outcomes: In successfully treated cases, mean resolution time is approximately 40 days, with visual acuity typically improving from worse than 20/1200 to better than 20/400 4