An Emerging Global Threat of Mycotic Keratitis Caused by Uncommon Fungal Species: A Systematic Review and Meta-Analysis.

Purpose: The purpose of this study was to analyze epidemiological characteristics, clinical spectrum, and treatment outcome of mycotic keratitis (MK) caused by uncommon species. Methods: The systematic review in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines has been registered on "PROSPERO" (CRD42023410825), whereas the systematic literature search was conducted on PubMed, Cochrane, Google Scholar, and Semantic Scholar on uncommon MK from January 1963 to March 2023. The main keywords for the literature search comprised: "mycotic keratitis," "fungal keratitis," "keratomycosis," "oculomycosis," "uncommon," "rare," "emerging," "atypical," "unusual," and various combinations of it. Results: The study identified a pool of 13,662 articles. Five hundred sixty-six studies were deemed suitable, and 186 studies met the inclusion criteria to ascertain the pooled prevalence. A total of 154 uncommon fungal species/genera were identified among 61 countries. Australia exhibited the highest pooled prevalence, whereas India reported the maximum number of cases, genera, and species. Clinical presentation varied from mild to severe disease with unequivocal response to standard therapeutic regimes. Microbiologically proven species with reported sensitivity had better visual and structural outcomes. Conclusions: The study provides the first-ever global prevalence estimate of MK caused by uncommon species, estimating 154 fungal genera/species with varying severity, assuming that several culture-negative cases with specific predispositions would also qualify as cases of MK. Microbiologically proven species with reported sensitivity have better visual and structural outcomes. Cases that fail to respond to standard therapy should be re-evaluated for uncommon species with a high index of suspicion. Prompt diagnosis with culture and sensitivity analysis, PCR or in vivo confocal microscopy (IVCM)-based test and timely treatment remain the most important factors in salvaging visual and structural function. Translational Relevance: This review catalogues the epidemiological, clinical, and morphological traits of rare fungi implicated in atypical MK and also provides a global prevalence estimate. Further, it emphasizes the role of implementation of specialized diagnostic techniques and collaborative efforts to combat the visual disability stemming from afflictions due to rare or atypical fungal species. Information on continent and country wise prevalence of atypical species would be helpful in appropriate management of such cases, in event of inconclusive diagnosis and consequent suboptimal response to treatment.