Efficacy and safety of intracameral amphotericin B for fungal keratitis: A systematic review and meta-analysis.

BACKGROUND: Fungal keratitis remains a leading cause of corneal blindness in tropical and subtropical regions. The limited corneal penetration of topical antifungals has prompted investigation into intracameral amphotericin B (ICAMB), which delivers higher intraocular concentrations beyond the corneal epithelium and stroma, although the corneal endothelium remains a pharmacologic barrier.

OBJECTIVE: To systematically evaluate the efficacy and safety of ICAMB in fungal keratitis and synthesize current evidence from randomized and observational comparative studies, together with descriptive case-based evidence.

METHODS: This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline using PubMed, Scopus, Cochrane Library, and Google Scholar through May 2025. Eligible studies assessed ICAMB, alone or in combination with topical therapy, in confirmed or clinically suspected fungal keratitis. Outcomes included ulcer healing rate, mean healing time, visual acuity, hypopyon resolution, need for keratoplasty, and adverse events. Fixed- or random-effects models were applied according to statistical heterogeneity, and Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess evidence certainty.

RESULTS: Seventeen studies (n = 491 eyes) were included. ICAMB significantly improved ulcer healing rate (odds ratios 1.8, 95% confidence intervals [CI]: 1.6-1.9, P < 0.001), shortened mean healing time by 4.27 days (95% CI: -5.8 to -2.8, P < 0.001), and reduced hypopyon duration by 14.6 days (95% CI: -17.4 to -11.8, P < 0.001). The requirement for therapeutic keratoplasty decreased significantly (logit event rate -0.71, P < 0.001). Improvement in visual acuity was modest but significant (standardized mean difference 0.49, P < 0.001). Heterogeneity across pooled analyses was negligible (I² = 0% in the reported pooled endpoints), and GRADE indicated moderate-to-high certainty for efficacy. Regarding safety, no definite ICAMB-attributable ocular toxicities (e.g., corneal endothelial decompensation, lens toxicity, retinal toxicity, or sustained intraocular pressure elevation temporally and causally linked to ICAMB) or systemic toxicities were reported at commonly used doses (typically ≤10 µg/0.1 mL); however, inflammatory and structural complications of fungal keratitis (e.g., uveitis, hypopyon, progressive thinning, perforation) were variably reported during follow-up and should not be interpreted as drug toxicities without explicit causal attribution.

CONCLUSIONS: ICAMB was associated with improved healing and reduced surgical intervention in fungal keratitis without reported definite ICAMB-attributable ocular or systemic toxicity at commonly used doses. Although the evidence is primarily observational, the consistency of effect across cohort and case-series data supports its potential role as an adjunctive therapy in severe or refractory fungal keratitis. Conventional treatment in this context refers to standard topical antifungal therapy (e.g. natamycin, voriconazole). Available data on species-specific amphotericin susceptibility and ocular surface disease parameters in Candida-associated cases were limited, heterogeneous, and not suitable for pooled analysis. Future trials should include standardized outcome definitions and controlled comparisons to validate these findings.