Treatment of Endogenous Fungal Endophthalmitis with Systemic and Intravitreal Voriconazole: A Clinical and Penetration Pharmacokinetic Study

Abstract

Abstract: : Purpose:Voriconazole is a new generation triazole antifungal agent that has been shown to achieve therapeutic intraocular levels after systemic administration. It has a spectrum of coverage encompassing those organisms most commonly responsible for endogenous fungal endophthalmitis. This series describes the experience at two centers in using voriconazole through systemic and intravitreal routes. Methods:A retrospective review of four patients from the Barnes Retina Institute and the Cullen Eye Institute who were diagnosed with endogenous fungal endophthalmitis and who were subsequently treated with voriconazole through oral, intravenous, or intravitreal routes. Post–mortem intraocular voriconazole concentrations on a fifth patient will be presented as well. Results:All patients had systemic cultures positive for Candida species. The first patient had complete resolution of ocular mycosis with oral voriconazole treatment. The second patient received 100mcg of intravitreal voriconazole (final vitreous concentration 25 mcg/ml) followed by oral voriconazole treatment and responded favorably. Our third patient with bilateral disease responded well to intravenous voriconazole, however, had a recurrence when discharged on oral voriconazole. This patient had a history of bowel resection with an ileostomy; therefore, it was felt that absorption of oral voriconazole may have been inadequate. Therefore, she was treated with bilateral amphotericin–B intravitreal injection and outcome will be reviewed. Patient number four had prompt resolution of fungal endophthalmitis after being treated with intravenous voriconazole. Our fifth patient was an individual who presented with multi–system failure and passed away one week after initiating intravenous voriconazole for systemic candidiasis. Post–mortem high–performance liquid chromatography analysis of the aqueous and vitreous revealed intraocular voriconazole concentrations of 1.52 mcg/ml and 1.12 mcg/ml, respectively (MIC₉₀ of C. albicans is 0.06 mcg/ml). Conclusions:Treatment of intraocular mycotic infection is challenging. Voriconazole appears to be a powerful weapon to add to our existing armamentarium against fungal endophthalmitis. Further studies are warranted to precisely define the role of this agent.

Keywords: antibiotics/antifungals/antiparasitics • endophthalmitis • fungal disease