Retinal Function of Rabbits Assessed by ERG before and after Induction of Ocular Aspergillosis and Treatment by the Anti–microbials, Micafungin and Amphotericin B

Abstract

Abstract: : Purpose: To compare the effectiveness of Micafungin(FK463, Fujisawa), a new anti–fungal agent, and amphotericin B, a standard agent for treatment of fungal infection, in preserving retinal function measured by electroretinogram (ERG) following induction of endophthalmitis by intravitreal injection of Aspergillus fumigatus. Methods: Baseline full–field ERG was recorded from anesthetized rabbits OU within 24 hr prior to intravitreal injection of fungus. A 0.06 ml suspension containing 10⁶ to 10⁷ colony forming units of A. fumigatus/ml was injected into the central vitreous OD and 0.06 ml 0.9% sterile saline was injected intravitreally OS. After 12 hr, rabbits were treated by intravitreal injections into both eyes with: saline N=4 (0.06 ml 0.9% sterile saline), or Micafungin N=5 (150 µg in 0.06 ml solution), or amphotericin B N=4 (75 µg in 0.06 ml solution). Fungal infection was confirmed by indirect ophthalmoscopy. Rabbits were followed until the b–wave amplitude of the ERG OD attained a criterion value of less than 30% of baseline amplitude or until 8 days had elapsed. ERGs were also recorded at 24 and 72 hr after injection of the fungus. ERG b–wave amplitudes at baseline and at 72 hr were normalized relative to baseline and analyzed by one way ANOVA with post–hoc Newman–Keuls comparisons. Criterion for significance was p<0.05. Results: In OS, the amplitudes in the saline group were not different from baseline or from those of the Micafungin group, but the amplitudes in the amphotericin B group were significantly depressed relative to the saline group at 72 hr. All rabbits in the saline group attained the criterion amplitude in OD between 24 and 72 hr. In OD, the amplitude of the ERG in the Micafungin group (mean of 30% of baseline value) was significantly greater than that of the saline group but significantly smaller than that of the amphotericin B group which had mean amplitudes about 50% of the baseline value at 72 hr. Conclusions: The data indicate that retinal function is significantly affected by amphotericin B but not by Micafungin in eyes without endophthalmitis. These data may reflect the known toxicity of amphotericin B and suggest that Micafungin is less toxic. There is a significant preservation of retinal function in eyes with endophthalmitis treated by Micafungin and in those treated by amphotericin B, but the extent of preservation is significantly greater in the amphotericin B treated animals within the 72 hr investigation period.

Keywords: endophthalmitis • electroretinography: non–clinical • fungal disease