Candida Endophthalmitis: Focus on Current and Future Antifungal Treatment Options

Abstract

Candida endophthalmitis is a sight-threatening manifestation of disseminated candidiasis. The occurrence of endogenous candida endophthalmitis in patients with candidemia has ranged from 0-45% in the published literature. In critically ill patients, it has even been associated with increased mortality. In recent years, use of newer antifungal therapies for invasive candidiasis has increased given the rise in infections with non-albicans species of Candida. To identify current practices of the management of endogenous candida endophthalmitis and relevant antifungal drug research in this disease state, we conducted a MEDLINE search (1967-2006) and bibliographic search of the English-language literature. Treatments for candida endophthalmitis have not been evaluated through well-designed, well-powered clinical trials. Data have mainly been presented in case reports, case series, animal studies, pharmacokinetic studies, and as small subsets of larger trials. Traditional systemic therapies have been amphotericin B with or without flucytosine or fluconazole. Cure rates with antifungal drugs alone appear to be much higher in patients with chorioretinitis than in endophthalmitis with vitreal involvement. Pars plana vitrectomy with or without intravitreal amphotericin B injections has been advocated particularly for patients with moderate-to-severe vitritis and substantial vision loss. Information on new antifungal agents for endophthalmitis is limited, despite increasing use in patients with candidemia. Voriconazole may be a particularly attractive agent to consider for infections with fluconazole-resistant, voriconazole-susceptible strains. The current patchwork of animal studies and small patient reports provide clinicians with some insight into the role of newer agents in the treatment of candida endophthalmitis. In general, it appears that chorioretinitis infections can be more readily cured with most systemic antifungal agents, whereas more aggressive treatment, often including vitrectomy with or without intra-vitreal antifungal administration, is needed for patients with endophthalmitis with vitritis.

Incidence and Risk Factors of Ocular Infection Caused by Staphylococcus aureus Bacteremia

“…Ocular infection caused by candidemia is well known (15,19,20). In one prospective study, the incidence of eye involvement was 16%, and that of endophthalmitis was 1.6% (15).…”

Aqueous Humor Concentrations of Topically Administered Caspofungin in Rabbits

“…This newer antifungal agent was therefore the first showing intraocular penetration due to lower protein binding and improved water solubility. However, fluconazole lacked a broad spectrum of coverage against many of the commonly encountered organisms found to cause fungal endophthalmitis [7] .…”

Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part II: Retinal Toxicity of Current and New Drugs

“…Amphotericin B has been traditionally used for the treatment, either systemically or intravitreally usually injected at doses varying from 1 to 50 g. In one study with the application of escalating doses from 10, 20, 30 to 50 g, the 3 higher doses of amphotericin B appeared to be associated with stronger degrees of retinal toxicity [32] . Based on animal experiments, intravitreal amphotericin B in doses of 5 or 10 g remains an appropriate therapeutic option for patients with severe fungal endophthalmitis, for instance secondary to Aspergillus [32] .…”

“…A single intravitreal injection of fluconazole at a concentration of 100 g/ml and higher caused harmful retinal changes with disorganization of the photoreceptor outer segments [34] . Clinical experience revealed that intravitreal injection of 10 g/0.1 ml fluconazole may be the safe dosage for intraocular fungal infection [32] .…”