title: Intravitreal voriconazole: an electroretinographic and histopathologic study.
abstract: BACKGROUND
  Voriconazole, a novel triazole antifungal agent, presents potent activity against a broad spectrum of yeast and molds.
  
  
  OBJECTIVE
  To determine whether voriconazole could be safely used as an intravitreal agent in the treatment of fungal endophthalmitis.
  
  
  METHODS
  Retinal toxicity of voriconazole was examined in a rodent animal model. Voriconazole solutions were serially diluted and injected intravitreally into the eyes of normal adult Sprague-Dawley rats so that the final intravitreal concentrations were 5 microg/mL, 10 microg/mL, 25 microg/mL, 50 microg/mL, and 500 microg/mL (n = 3 for each concentration group). Saline was injected into the fellow eyes of all animals as controls. Three weeks after injections, electroretinograms were measured, and eyes were subsequently enucleated for histologic examination.
  
  
  RESULTS
  In electroretinographic studies, maximum scotopic b-wave, intensity needed for half saturation, and saturated a-wave amplitude were measured. There was no statistically significant difference in these parameters recorded between control eyes and voriconazole-injected eyes in any concentration groups. Histologic examination with light microscopy did not reveal any retinal abnormality in the eyes with 5 to 25 microg/mL of intravitreal voriconazole. In the eyes with 50 microg/mL and 500 microg/mL of voriconazole, small foci of retinal necrosis were occasionally observed in the outer retina, especially in the eyes with 500 microg/mL of voriconazole.
  
  
  CONCLUSIONS
  Our results demonstrate that intravitreal voriconazole of up to 25 microg/mL [corrected] causes no electroretinographic change or histologic abnormality in rat retinas. This indicates that voriconazole is a safe antifungal agent for intravitreal injection in rodents and may be used in the treatment of human fungal endophthalmitis following further study.
authors.affiliation: Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.forename: Mark E
authors.initials: ME
authors.lastname: Pennesi
authors.forename: Kekul
authors.initials: K
authors.lastname: Shah
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Qiao
authors.forename: Seenu M
authors.initials: SM
authors.lastname: Hariprasad
authors.forename: William F
authors.initials: WF
authors.lastname: Mieler
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Wu
authors.forename: Eric R
authors.initials: ER
authors.lastname: Holz
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D004596:Electroretinography / Q000187:drug effects*; D009877:Endophthalmitis / Q000188:drug therapy / Q000382:microbiology; D015821:Eye Infections, Fungal / Q000188:drug therapy; D007267:Injections; D009883:Ophthalmic Solutions / Q000633:toxicity; D011743:Pyrimidines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000473:pathology*; D014230:Triazoles / Q000633:toxicity*; D014822:Vitreous Body; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D009883:Ophthalmic Solutions; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole