J Med Microbiol. 2025 Dec;74(12). doi: 10.1099/jmm.0.002106.
ABSTRACT
Introduction. Fungal keratitis, particularly in tropical and subtropical regions, poses significant therapeutic challenges due to biofilm formation by fungal pathogens. These biofilms confer increased resistance to antifungal treatments and are associated with poorer clinical outcomes.Hypothesis/Gap Statement. Despite growing recognition of their impact, there remains a lack of comprehensive synthesis on the role of fungal biofilms in corneal ulcers.Aim. This study aims to determine the impact of and how biofilm formation influences the chronicity and treatment outcomes in fungal corneal ulcers.Methodology. A comprehensive literature search was performed across PubMed, ScienceDirect, Scopus and the Cochrane Library in April 2025. Only English articles were included, and animal studies were excluded. Eligible studies included clinical and in vitro investigations that assessed biofilm formation in fungal corneal ulcers and its impact on antifungal susceptibility and treatment outcomes. This systematic review and meta-analysis were conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 guidelines and registered under PROSPERO (an international systematic review registry, ID:CRD420251017502). Independent data extraction was done by two reviewers. Data on MICs were synthesized using random-effects models, and heterogeneity was assessed with I² statistics and Cochran’s Q test. Clinical outcomes were analysed narratively due to reporting variability.Results. Seven studies were included, spanning Brazil, India, China and Mexico, and covering both in vitro and clinical designs. Meta-analysis showed significantly increased MIC values for biofilm-forming fungal isolates: amphotericin B [pooled log₂ fold change=5.31; 95% confidence interval (CI): 2.92-7.70], voriconazole (6.06; 95% CI: 2.25-9.87) and natamycin (1.25; 95% CI: 0.48-2.02). High heterogeneity was noted for amphotericin B and voriconazole, while results for natamycin were consistent. Narrative synthesis of clinical data indicated that biofilm formation is associated with prolonged healing times, increased recurrence rates, reduced visual acuity and higher complication risks.Conclusion. Biofilm formation by fungal pathogens significantly reduces antifungal susceptibility and worsens clinical outcomes in fungal keratitis. Elevated MIC, delayed healing and increased rates of complications emphasize the need for targeted biofilm-disrupting therapies and standardized diagnostic protocols. Future research should focus on developing clinical strategies that integrate biofilm assessment to improve patient outcomes.
PMID:41411030 | DOI:10.1099/jmm.0.002106
