Intrastromal Antifungal Injection for Fungal Keratitis
Intrastromal voriconazole injection (50 µg/0.1 mL) should be considered for deep recalcitrant fungal keratitis that fails to respond to intensive topical antifungal therapy (natamycin 5% and/or voriconazole 1%) combined with systemic antifungals after 7-14 days of treatment. 1, 2
Primary Indications for Intrastromal Antifungal Injection
The evidence supports intrastromal voriconazole specifically for:
- Deep stromal involvement extending beyond mid-stromal level that is not responding to topical therapy 1, 2
- Recalcitrant fungal keratitis showing progressive worsening or no improvement after 1-2 weeks of maximal topical antifungal therapy (hourly natamycin 5% plus topical voriconazole 1%) combined with oral antifungals 3, 1, 4
- Large infiltrates (mean area >30 mm²) with or without hypopyon that demonstrate poor penetration of topical agents 2
- Deep fungal abscess in the corneal stroma where conventional topical medications cannot achieve adequate tissue levels 4
Clinical Context and Evidence Quality
The 2024 American Academy of Ophthalmology guidelines acknowledge that "there is variable evidence on the efficacy of intrastromal injection of antifungals" for fungal keratitis 5. However, this statement reflects the lack of large randomized controlled trials rather than evidence of inefficacy. The available case series consistently demonstrate benefit in specific clinical scenarios.
Technical Approach When Indicated
When proceeding with intrastromal injection:
- Inject voriconazole 50 µg in 0.1 mL using a 30-gauge needle at the junction of clear cornea and infiltrates 3, 1, 4
- Create a circumferential barrage by injecting in five divided doses around the infiltrate to form a depot of drug around the lesion 1, 2
- Continue intensive topical and systemic antifungal therapy concurrently—intrastromal injection is an adjunct, not a replacement 3, 1, 4
- Repeated injections may be necessary in approximately 15% of cases if initial response is inadequate 2
Expected Outcomes and Response Patterns
Based on the strongest case series evidence:
- 72% resolution rate in deep recalcitrant cases when used appropriately 2
- Mean resolution time of approximately 40 days after intrastromal injection 1
- Smaller ulcers respond better than larger lesions 2
- Visual acuity improvement from worse than 20/1200 to better than 20/400 in most successful cases 1
Organism-Specific Considerations
Fusarium species show suboptimal response to intrastromal voriconazole compared to Aspergillus species 2. In one series, Fusarium was responsible for 6 of 7 treatment failures despite intrastromal injection 2. However, some Fusarium cases do respond, particularly when combined with aggressive topical therapy 3, 6.
Aspergillus species demonstrate better response rates to intrastromal voriconazole, with 8 of 8 cases in one series showing favorable outcomes 1.
Critical Pitfalls to Avoid
- Do not use intrastromal injection as first-line therapy—it is reserved for cases failing conventional treatment 1, 4, 2
- Never discontinue topical therapy after intrastromal injection; continued hourly topical application is critical for favorable outcomes 3
- Avoid corticosteroids in fungal keratitis, as steroids are contraindicated and increase the risk of requiring penetrating keratoplasty 7, 8
- Monitor closely for perforation—approximately 15-20% of deep recalcitrant cases may still progress to perforation requiring therapeutic keratoplasty despite intrastromal injection 1, 2
When NOT to Use Intrastromal Injection
Do not proceed with intrastromal injection if:
- The infection is responding adequately to topical therapy alone
- The infiltrate is superficial (anterior stroma only)
- Impending or frank perforation is present—these cases require urgent surgical intervention 5
- The patient has not yet received adequate trial of intensive topical therapy (minimum 7-14 days)
Surgical Alternatives for Treatment Failures
If intrastromal voriconazole fails or perforation occurs: