Intravitreal voriconazole: in vitro safety-profile for fungal endophthalmitis.
BACKGROUND
Fungal endophthalmitis is a rare but sight-threatening disease. Despite an expanding range of fungal pathogens, there are only few therapeutic agents for its treatment available. Voriconazole is a second-generation synthetic triazole with a broad action against yeasts and molds. The current study investigates the safety of Voriconazole for intravitreal application in a cell culture model.


METHODS
Primary human retinal pigment epithelium cells (RPE) and primary human optic nerve head astrocytes were treated with concentrations of Voriconazole ranging from 25 microg/mL to 10 mg/mL. Possible toxic effects and IC50 were evaluated after 24 hours and under conditions of oxidative stress. By treating the RPE cell lines with tumor-necrosisfactor alpha (TNF-alpha), lipopolysaccharides (LPS), and interleukin-6 (IL-6) the effects of Voriconazole on cellular viability under conditions of inflammation were investigated. Toxicity was evaluated by colorimetric measuring the inhibition of RPE cell proliferation (MTT). Additionally cell viability was quantified by a microscopic live-dead-assay.


RESULTS
Concentrations <250 microg/mL Voriconazole had no influence neither on RPE nor on optic nerve head astrocytes cell proliferation and cell viability when administered for 24 hours and under oxidative stress. When preincubated with tumor-necrosis-factor alpha, lipopolysaccharides and interleukin-6 for 24 hours and subsequently treated with Voriconazole at concentrations up to 250 microg/mL for 24 hours no significant decrease in proliferation and viability was observed.


CONCLUSIONS
This study showed that no significant toxicity existed for Voriconazole in vitro on primary RPE and optic nerve head astrocytes when administered in therapeutic concentrations up to 250 microg/mL.
Kernt
Marcus
M
Department of Ophthalmology, Ludwig Maximilian University, Munich, Germany. marcus.kernt@med.uni-muenchen.de
Neubauer
Aljoscha S
AS
De Kaspar
Herminia Mino
HM
Kampik
Anselm
A
D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003124:Colorimetry; D009877:Endophthalmitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015821:Eye Infections, Fungal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007267:Injections; D008875:Middle Aged; D018384:Oxidative Stress; D011743:Pyrimidines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014822:Vitreous Body; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole