Impact of Iontophoresis and PACK-CXL Corneal Concentrations of Antifungals in an In Vivo Model

Cornea. 2018 Nov;37(11):1463-1467. doi: 10.1097/ICO.0000000000001696.


Purpose: To investigate voriconazole (VRZ) penetration and fungal load in the cornea after applying VRZ therapy with various treatment combinations in a fungal keratitis model.

Methods: Fifty-four eyes of 27 young albino rabbits were provided for this experimental study. Twelve corneas were inoculated with Candida albicans, 12 corneas were inoculated with Fusarium solani, and 6 eyes were selected as controls. Infected corneas received various treatment combinations including VRZ 1% drop therapy alone, VRZ 1% plus amphotericin B 1% drop combination therapy, iontophoretic VRZ therapy, and VRZ 1% drop therapy after corneal cross-linking. Fungal load was measured by log reduction, and VRZ levels were quantified by liquid chromatography-tandem mass spectrometry.

Results: Iontophoresis-assisted VRZ application showed the highest antifungal activity against F. solani keratitis (4-log reduction) and C. albicans keratitis (5-log reduction) compared with other treatment applications. VRZ levels were also found to be the highest in corneas that received iontophoretic VRZ treatment (3.6313 ± 0.0990 ppb for F.solani keratitis and 1.7001 ± 0.0065 ppb for C. albicans keratitis) compared with other treatment applications.

Conclusions: Iontophoresis seems to provide the highest VRZ concentration and highest antifungal activity in the cornea compared with other treatment applications for C. albicans and F. solani keratitis.

MeSH terms

  • Animals
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / therapeutic use*
  • Candida albicans / isolation & purification
  • Candidiasis / drug therapy
  • Collagen / metabolism
  • Cornea / metabolism*
  • Cornea / microbiology
  • Cross-Linking Reagents / therapeutic use*
  • Disease Models, Animal
  • Eye Infections, Fungal / drug therapy*
  • Fusariosis / drug therapy
  • Fusarium / isolation & purification
  • Iontophoresis*
  • Keratitis / drug therapy
  • Photochemotherapy / methods*
  • Rabbits
  • Ultraviolet Rays
  • Voriconazole / pharmacokinetics
  • Voriconazole / therapeutic use*


  • Antifungal Agents
  • Cross-Linking Reagents
  • Collagen
  • Voriconazole