Topical Voriconazole as a Novel Treatment for Fungal Keratitis

Abstract

Paecilomyces lilacinus is a fungal pathogen which is generally resistant to amphotericin B and certain other antifungals and is an uncommon cause of devastating fungal keratitis. In the present studies, we evaluated topical voriconazole as therapy for P. lilacinus keratitis in rabbits. Thirty eyes of 15 rabbits were studied. In five animals, the uninfected left eye was treated twice daily with voriconazole (drug control, uninfected eye). In these same animals, the right eye was infected with P. lilacinus but not treated with voriconazole (infection control eye). By day 5, the infection controls had lesions of >2.4 mm in diameter, with conjunctivitis and severe hypopyon, and were sacrificed. In the other 10 rabbits (voriconazole treatment), the right eyes were infected with P. lilacinus and treated with voriconazole beginning on day 3 after infection. Voriconazole therapy caused lesions to decrease during 8 days of therapy, after which rabbits were sacrificed (11 days postinfection). Hyphal masses were present in the control infected eyes and absent in treated infected eyes. Voriconazole was detected in all tissues of treated eyes. Topical voriconazole is effective treatment for P. lilacinus experimental keratitis, and it penetrates more deeply than the corneal tissue.

Topikal tedaviye dirençli Aspergillus fumigatus keratitinde intrastromal vorikonazol uygulaması

“…Currently available topical antifungal drugs have limitations such as poor penetration into the eye, limited spectrum of activity and surface toxicity (3)(4)(5). In this study, the result of using intrastromal voriconazole in a Aspergillus fumigatus keratitis non-responsive to topical and systemic conventional amphotericin B therapy is reported.…”

“…Voriconazole and other new triazoles are, at least theoretically, superior to the traditionally used antifungal agents (3,4). This study presents a patient with intractable fungal keratitis treated with an intrastromal injection of voriconazole and topical voriconazole to further elucidate the effectiveness of voriconazole for the treatment of fungal keratitis.…”

“…Most available antifungal agents are fungistatic (3). This limitation, together with the poor topical penetration of fungal agents, has prompted ophthalmologists to seek more potent antifungal agents and better routes of application.…”

Aqueous humor concentration of voriconazole after topical administration in rabbits

“…Several authors have reported topical attempts at treatment of fungal keratitis with voriconazole, with variable success. Despite the treatment failure in two patients with topical voriconazole reported by Giaconi in 2006 [7], the majority of reports have shown effective clinical outcome and are therefore promising [8,9].…”

Uso de voriconazol tópico en queratitis por alternaria

“…En los modelos experimentales, la inmunosupresión de los tejidos oculares inducida mediante la administración sistémica de metilprednisolona, conduce a un incremento de la severidad de la infección y a una persistencia más prolongada del hongo en la córnea (2). Estudios previos han demostrado la eficacia del voriconazol en el tratamiento de las queratitis fúngicas (3,4). En nuestro caso se utilizó voriconazol tópico al 1% y sistémi-co, evidenciándose una mejoría significativa en la inflamación corneal.…”