Toxicity of Intravitreal Fluconazole in Rabbits: An Extended Abstract

Abstract

Fungal endophthalmitis has been associated with a high degree of morbidity; this, together with an increase in the postsurgical incidence of the infection and the inadequacy of currently available therapies, has emphasized the need for safe and effective treatment alternatives [1]. Optimal therapeutic regimens for fungal endophthalmitis have not been defined. Several studies have reported encouraging results in the treatment of mycotic intraocular infections with intravitreous injection of amphotericin B alone or in combination with vitrectomy. Intravitreous administration of amphotericin B in conjunction with parenteral support has also been useful in the treatment of patients with fungal endophthalmitis. However, toxic effects following both systemic and intraocular administration make this agent less than ideal [2-4]. Reports indicate that parenterally administered miconazole, despite having few toxic effects, is generally less effective than amphotericin B in the treatment of both experimental and clinical fungal endophthalmitis [5, 6]. The solubility of miconazole in aqueous solution is poor, and preliminary tests have shown that doses of >40 gtg dissolved in 100%7o DMSO are toxic when injected intravitreally in rabbit eyes. The toxicity was considered to be due to miconazole and not to the solvent DMSO [7]. Intraocular toxicity studies were performed in New Zealand white rabbits. Our results indicate that fluconazole at concentrations of up to 100 ig/0.1 mL can be injected into the vitreous cavity in these animals without producing toxic effects [8]. These findings suggest a possible role for intravitreal injection of fluconazole in the treatment of exogenous fungal endophthalmitis in humans. Savani and associates [9] found that fluconazole exhibited good intravitreal penetration (21.5 ? 0.1