What drug is used for antifungal intrastromal injection in fungal keratitis?

Antifungal Intrastromal Injection for Fungal Keratitis

For intrastromal injection in fungal keratitis, voriconazole 50 μg/0.1 mL is the preferred agent, with amphotericin B 5-10 μg/0.1 mL as an alternative or combination option.

Primary Agent: Voriconazole

• Voriconazole at a dose of 50 μg in 0.1 mL (0.05 mg/0.1 mL) is the most commonly used intrastromal antifungal agent for fungal keratitis 1
• This concentration provides effective tissue levels against both yeasts and molds, including Aspergillus species which are the predominant organisms in fungal keratitis 1
• Combined intrastromal voriconazole with topical therapy achieved complete resolution in 87.5% of persistent fungal keratitis cases that had failed topical therapy alone 1
• The mean number of injections required is approximately 9 (range 1-18), with complete epithelial closure achieved in a mean of 45 days 1

Alternative Agent: Amphotericin B

• Amphotericin B at 5-10 μg/0.1 mL can be used for intrastromal injection, with this dose achieving effective drug levels in the cornea that exceed the MIC90 for a wide spectrum of fungi and molds 2
• After a single intrastromal injection, therapeutic amphotericin B levels are maintained in the cornea for up to 7 days 2
• Intrastromal amphotericin B has been successfully used to eradicate fungal plaques in cases of recurrent fungal keratitis, offering a less invasive alternative to repeat penetrating keratoplasty 3

Combination Therapy Approach

• For persistent or severe fungal keratitis, combined intrastromal voriconazole (0.05 mg/0.1 mL) and intrastromal liposomal amphotericin B (0.01 mg/0.1 mL) provides synergistic benefit 1
• This combination is indicated when there is no improvement or progression despite at least 10 days of hourly topical voriconazole and amphotericin B 1
• The combination approach resulted in only 12.5% requiring therapeutic penetrating keratoplasty, with no cases requiring evisceration 1

Critical Contraindications

• Intrastromal injection must be avoided in impending or frank corneal perforation, extremely thin cornea (<200 microns), and active corneal melting with significant stromal loss 4
• The risk of iatrogenic perforation during needle insertion outweighs potential benefits when corneal integrity is severely compromised 4
• Cases with imminent perforation (within hours to days) should proceed directly to surgical intervention rather than intrastromal injection 4

Clinical Decision Algorithm

Step 1: Assess corneal structural integrity

• Measure corneal thickness and evaluate for active melting 4
• If thickness <200 microns or active melting present, proceed to surgical options 4

Step 2: Determine injection indication

• Consider intrastromal injection for deep stromal infiltration not responding to topical therapy after 10+ days 1, 5
• Intrastromal injection achieves steady-state drug levels and prevents subtherapeutic intervals 5

Step 3: Select agent(s)

• Use voriconazole 50 μg/0.1 mL as first-line for most fungal keratitis 1
• Add amphotericin B 10 μg/0.1 mL (or liposomal 0.01 mg/0.1 mL) for Aspergillus or persistent cases 1, 2

Step 4: Injection technique

• Administer injections every 2-3 days initially, then space based on clinical response 1
• Continue until complete epithelial closure and resolution of infiltrate 1

Important Caveats

• Fungal keratitis inherently has worse outcomes than bacterial keratitis, with larger infiltrates, slower re-epithelialization, and higher perforation rates at 3 months 4
• Topical therapy remains the mainstay and should be continued intensively alongside intrastromal injections 5
• Visual acuity typically improves significantly (mean improvement from 2.17 to 1.76 logMAR) with successful treatment 1
• The procedure can be performed in-office, avoiding the need for operating room procedures in many cases 3