Intrastromal Voriconazole and Amphotericin B for Fungal Keratitis: A Systematic Review and Meta-analysis

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Karanvir Gill¹, Arvin Zaker¹, Aaryamaan Verma¹

¹UBC Faculty of Medicine, Department of Ophthalmology and Visual Sciences, Vancouver, BC, Canada.

The Ocular Surface

|October 28, 2026

Abstract

Purpose:

To evaluate the efficacy and safety of intrastromal voriconazole (IS-VCZ) and intrastromal amphotericin B (IS-AMB) for fungal keratitis.

Methods:

PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library were searched from inception for randomized trials, comparative observational studies, and case series evaluating IS-VCZ or IS-AMB. Random-effects meta-analyses were performed for comparative and single-arm outcomes.

Results:

Thirty-six studies were included: 33 evaluated IS-VCZ (732 eyes) and 7 evaluated IS-AMB (171 eyes), with four contributing to both groups. In uncontrolled single-arm analyses, pooled healing proportions were 79.1% (95% CI, 70.5%-85.7%) for IS-VCZ and 86.4% (95% CI, 71.9%-94.1%) for IS-AMB; these estimates were descriptive and do not establish treatment efficacy. Pooled therapeutic keratoplasty rates were 12.3% (95% CI, 6.7%-21.4%) and 13.2% (95% CI, 4.4%-33.4%), respectively. Compared with non-intrastromal therapies, IS-VCZ demonstrated no significant difference in clinical healing (OR 1.20, 95% CI 0.40-3.56), therapeutic keratoplasty (OR 1.29, 95% CI 0.59-2.82), or final visual acuity (MD 0.22, 95% CI -0.51 to 0.94). Comparative evidence remained limited, with wide confidence intervals across several outcomes. Comparative evidence for IS-AMB was limited and similarly demonstrated no significant differences in healing (OR 2.62, 95% CI 0.68-10.03), therapeutic keratoplasty (OR 0.45, 95% CI 0.02-8.23), or healing time (MD -5.64 days, 95% CI -25.05 to 13.77). Substantial heterogeneity was observed across most pooled outcomes.

Conclusions:

Current comparative evidence is insufficient to establish the efficacy of IS-VCZ or IS-AMB relative to existing antifungal therapies. Uncontrolled studies report favorable healing outcomes, but these findings cannot establish treatment efficacy. Intrastromal antifungal therapy may have a role as adjunctive or salvage treatment, but higher-quality comparative studies with standardized protocols are needed.

Keywords:

corneal ulcer fungal keratitis intrastromal amphotericin B intrastromal voriconazole keratomycosis meta-analysis systematic review therapeutic keratoplasty

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