Antifungal Therapy for Fusarium Keratitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PURPOSE: Fusarium keratitis is a leading cause of fungal corneal ulceration worldwide and is associated with substantial visual morbidity. Despite the availability of randomized controlled trial (RCT) data, optimal antifungal therapy remains debated. This study aims to define an evidence-based therapeutic hierarchy for F. keratitis using RCT evidence. METHODS: A systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. MEDLINE, EMBASE, and CINAHL were searched from inception to December 2025 for RCTs evaluating antifungal therapies in fungal keratitis with extractable Fusarium-specific data. Two independent reviewers performed study selection, data extraction, and risk of bias assessment using the Cochrane Risk of Bias 2.0 tool. Random-effects meta-analysis (DerSimonian-Laird) was used to pool outcomes. The primary outcome was best spectacle-corrected visual acuity (BSCVA, LogMAR). Secondary outcomes included corneal perforation and requirement for therapeutic penetrating keratoplasty. Certainty of evidence was assessed using the GRADE framework. RESULTS: Eleven RCTs comprising over 1800 participants were included. Meta-analysis demonstrated that topical natamycin 5% was associated with significantly improved visual acuity compared with topical voriconazole 1% (pooled mean difference -0.18 LogMAR, 95% confidence interval -0.30 to -0.05; I2 = 38%), corresponding to an improvement of approximately 2 Snellen lines. Natamycin was also associated with a substantial reduction in corneal perforation and requirement for therapeutic keratoplasty (pooled odds ratio 0.42, 95% confidence interval 0.22-0.80). The direction of effect was consistent across included trials, with low-to-moderate heterogeneity (I2 = 38%). Adjunctive systemic or intrastromal voriconazole did not demonstrate consistent benefit and was associated with increased adverse events. Evidence for alternative antifungal agents remains limited. CONCLUSIONS: Meta-analytic findings define a clear evidence-based therapeutic hierarchy in F. keratitis and establish topical natamycin 5% as the standard of care. Routine use of voriconazole is not supported in unselected patients. Further adequately powered, species-specific randomized trials are required to optimize treatment strategies in this vision-threatening condition.