title: Toxicity of topical antifungal agents to stratified human cultivated corneal epithelial sheets.
abstract: OBJECTIVE
  Prolonged use of topical antifungal agents may compromise corneal epithelial integrity. Here, we used an in vitro model of human stratified corneal epithelium to compare the ocular toxicity profiles of 4 different antifungal eye drops.
  
  
  METHODS
  Human corneal epithelial cell sheets were cultured in a serum-free medium containing 0.1% micafungin, 1% voriconazole, 5% pimaricin, 0.1% amphotericin B, or controls (saline or 5% glucose). Cell viability and barrier function were measured by WST-1 assay and carboxyfluorescein permeability assay, respectively. Cell migration was measured on a wound healing assay.
  
  
  RESULTS
  WST-1 assay and carboxyfluorescein permeability assay revealed that amphotericin B was the most toxic drug, followed by pimaricin, micafungin, and voriconazole. Cell migration on a wound healing assay was decreased in the following order, amphotericin B, pimaricin, micafungin, and voriconazole.
  
  
  CONCLUSIONS
  Topical micafungin and voriconazole appeared to be the least toxic to the corneal epithelium. Drug prescription should consider not only fungal species and susceptibility but also ocular toxicity and stage of treatment.
authors.affiliation: Department of Ophthalmology, University of Tokyo School of Medicine , Tokyo, Japan .
authors.forename: Mikiko
authors.initials: M
authors.lastname: Kimakura
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Usui
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yokoo
authors.forename: Suguru
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamagami
authors.forename: Shiro
authors.initials: S
authors.lastname: Amano
mesh_terms: D000666:Amphotericin B / Q000633:toxicity; D000935:Antifungal Agents / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054714:Echinocandins / Q000633:toxicity; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D055666:Lipopeptides / Q000633:toxicity; D000077551:Micafungin; D009883:Ophthalmic Solutions; D065819:Voriconazole / Q000633:toxicity; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D009883:Ophthalmic Solutions; D000666:Amphotericin B; D065819:Voriconazole; D000077551:Micafungin