In vivo evaluation of voriconazole eye drops efficacy in a rat Acanthamoeba polyphaga keratitis model

Abstract

PurposeAcanthamoeba keratitis is a sight‐threatening infectious disease. Its effective and safe medical therapy remains highly debated. The aim of this study is to test in vitro and in vivo voriconazole as a potential antiamoebic treatment for Acanthamoeba keratitis.MethodsIn vitro sensitivity of Acanthamoeba polyphaga to voriconazole was assessed using a commercially available viability assay. In vivo, Sprague‐Dawley male rats were injected in the left cornea stromal layer with trophozoites. Forty rats were divided into 3 groups, topically treated with 1% voriconazole eyedrop (hourly administrations for 3 days followed by every two hours for 11 days and followed every four hours for 7 days), orally treated with voriconazole (60 mg/kg/day), and control. At day 28, cornea and blood samples were collected and corneal scrapings were performed for bacterial and parasitological cultures and real‐time PCR analyses. Paraffin‐embedded corneas were analyzed. The plasma and corneal concentration of voriconazole was determined by high‐performance liquid chromatography.ResultsIn vitro, voriconazole inhibited Acanthamoeba polyphaga trophozoites proliferation with IC90 value of 6 μg/ml, however no cystical activity was found. Mean intracorneal concentration of voriconazole eyedrops after three days treatment was 5.6 +/‐ 4.4 ng / mg; after seven days treatment was 2.38 + /1.6 ng/mg; and after twenty one days treatment was 0.32 +/‐ 0.15 ng / mg. Clinical infection worsened in fewer rats between the 7th and the14th day post infection in the voriconazole eye drops group (1/10 rats) and the control group (9/10 rats) (p = 0.001).ConclusionsOur findings support the potential use of voriconazole as anti‐amoebic agents.