Retinal Function Assessed by ERG Before and After Induction of Ocular Aspergillosis and Treatment by the Anti-fungal, Micafungin, in Rabbits

Abstract

This study was conducted to evaluate the effectiveness of a new antifungal drug, micafungin, and standard antifungal drugs against endophthalmitis induced in a rabbit by intravitreal injection of Aspergillus fumigatus, an important fungal pathogen. Effectiveness was evaluated by the preservation of b-wave amplitude at 72 h after injection of the fungus relative to the b-wave amplitude at baseline before any intravitreal injections. A 0.06 ml inoculum of 10(6) conidia of A. fumigatus was injected into the vitreous of the right eye of all rabbits; and, 12 h later, a 0.06 ml solution containing one of 3 antifungal drugs or saline was injected into the vitreous of both eyes. All three antifungal drugs produced significant b-wave preservation at 72 h in infected eyes compared to that in infected eyes receiving saline injections. There was no statistically significant difference between the effects of micafungin and amphotericin B in the right eyes with fungal endophthalmitis, and both produced significantly more preservation of b-wave amplitude than voriconazole. Amphotericin B, but neither micafungin nor voriconazole produced significant reduction of the b-wave amplitude in the left eyes.

24(S)-Hydroxycholesterol protects the ex vivo rat retina from injury by elevated hydrostatic pressure

“…This drug is used clinically as an antifungal agent and inhibits CYP46A1 with relatively high potency 40 . Although the safety of intravitreous injection of voriconazole on retinal function has been described in rabbits 41 , voriconazole transiently impairs bipolar cell function in monkeys 42 and is associated with retinal dysfunction in rats following repeated systemic administration 43 . Recently, the effects of repeated doses of voriconazole on the vision of healthy human subjects was investigated in a double-blind, placebo-controlled study 44 .…”

Histological Effects of Intravitreal Injection of Antifungal Agents in New Zealand White Rabbits: An Electron Microscopic and Immunohistochemical Study

“…In a similar study by Harrison et al, intravitreal injection of micafungin showed similar results to standard treatment with voriconazole and amphotericin B in A. Fumigatus keratitis, which was demonstrated by the maintenance of b-wave length in the ERG for all three antifungal therapies compared to the control group that received saline [ 60 ]. According to Hiraoka et al, topical application of micafungin (0.1%) was evaluated against the control group in uninfected rabbit eyes [ 63 ].…”

“…On the other hand, voriconazole has a disadvantage in maintaining retinal function compared to the other two substances, requires higher concentrations, and is considered more toxic than micafungin. Also, this protocol refers to the administration of only one intravitreal injection and not multiple [ 60 ].…”

Persistently Vitreous Culture–Positive Exogenous Fungal Endophthalmitis

“…Untreated, Aspergillus can cause diminution of the a-waves and b-waves on electroretinogram within 72 hours of infection in animal models. 10 Furthermore, active persistent infection can be difficult to differentiate from residual non-infectious inflammation; in these cases, repeat vitreous cultures can help guide further treatments.…”