title: Toxicity of intrastromal voriconazole injection on corneal endothelium in rabbits.
abstract: OBJECTIVE
  The aim of this study was to evaluate the toxicity of intrastromally injected voriconazole on corneal endothelial cells in rabbits.
  
  
  METHODS
  In total, 32 eyes of 16 rabbits (8 eyes for each group) were divided into 4 groups according to the concentration of voriconazole [group A: 50 μg/0.1 mL (0.05%), group B: 100 μg/0.1 mL (0.1%), group C: 250 μg/0.1 mL (0.25%), or group D: 500 μg/0.1 mL (0.5%)]. Right eyes were injected intrastromally with voriconazole at concentrations of 50 μg/0.1 mL, 100 μg/0.1 mL, 250 μg/0.1 mL, or 500 μg/0.1 mL. Left eyes were injected intrastromally with isotonic saline as controls. Central corneal thickness and endothelial cell counts were measured before and at 6 hours, 1 day, and 1 week after the injection was given. Corneas were then harvested for transmission electron microscopy.
  
  
  RESULTS
  Only the 0.5% group did not significantly recover from corneal edema 1 week after the injection (P = 0.167, P = 0.051, P = 0.086, P = 0.001 in groups A-D, respectively). There were significant differences in endothelial cell counts for the 0.1% and 0.25% groups (P = 0.077, P = 0.019, P = 0.008 in groups A-C, respectively). Transmission electron microscopy evaluation revealed definite necrotic changes in endothelial cells at concentrations of 0.1%, 0.25%, and 0.5%, but only microstructural changes at a concentration of 0.05%.
  
  
  CONCLUSIONS
  Our results suggest that voriconazole could be injected safely into the intrastromal layer at a concentration of 0.05% with low endothelial cell toxicity. However, injections should be administered with caution because of the risk of microstructural damage.
authors.affiliation: *Department of Ophthalmology and Visual Science, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; †Department of Ophthalmology, Air Base Hospital of 18th Fighter Wing, Republic of Korea Air Force, Korea; ‡Department of Ophthalmology and Visual Science, St Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Park
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Lee
authors.forename: Sung Kun
authors.initials: SK
authors.lastname: Chung
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D002452:Cell Count; D003316:Corneal Diseases / Q000139:chemically induced* / Q000473:pathology; D003319:Corneal Stroma / Q000187:drug effects* / Q000648:ultrastructure; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000648:ultrastructure; D056965:Injections, Intraocular; D008297:Male; D046529:Microscopy, Electron, Transmission; D011817:Rabbits; D065819:Voriconazole / Q000633:toxicity*
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole