Comparison Of Efficacy Of Oral, Topical And Oral & Topical Itraconazole Treatment In Experimental Aspergillus Keratitis

Objective: To investigate the therapeutic role of topical, oral and combine itraconazole treatment using a rabbit model of Aspergillus fumigatus keratitis.Methods: The epithelium was removed from the central cornea and a inoculum of Aspergillus fumigatus blastoconidia was placed on the corneal surface and covered with a soft contact lens. Forty-eight hours later, the thirty-two rabbits were randomly divided into four groups. Topical group eight rabbits were treated with topical itraconazole (1%, eight times daily), oral group eight rabbits received oral itraconazole (40mg/kg/bid), combine group eight rabbits were treated both topical itraconazole (1%, eight times daily) and oral itraconazole (40mg/kg/bid), untreated controls eight rabbits. The eyes were examined and photographed with a slit-lamp 1, 3, 6, 10, 15, 20 and 25 days after inoculation and an observer graded the corneas in a masked fashion. Corneal scraping, cultures were taken on days 3, 6, 15 and 25 for fungus growth.Results: 1. Comparing the process of clinical pathology found that four groups consistent performance on 1 to 3 days. In the treated 6 day after, the three treatment groups in various points had significant lower the pathological changes and the course period than the control group. After day 15, the topical and combine groups had significant lower than oral groups, but no difference between topical and combine groups.2. At the beginning of treatment, 1 to 3 days, the slit-lamp scores did not differ among four groups. However, after days 6 the three treated groups had statistically significant lower scores compared to the untreated controls (P<0.01). On day 15 the topical and combine classes had statistically significant lower marks compared to the oral groups (P<0.05), but no distinguished difference was observed between topical and combine groups at any examination point.3. Three treated groups, complications such as hypopyon, corneal perforation and corneal neovascularization rate was significantly lower than the control group and there was a significant difference (P<0.01). On day 6, there were significantly lower positive fungal cultures in three treatment groups compared to the control (P<0.05). However, all cultures were negative on days 15-25.Conclusions: 1. We improved the method of experimental fungal keratitis model which has a high rate of success used by soft contact lens, the method can be used for the model of fungal keratitis.2. Our study showed that topical, oral and combine itraconazole were effective in lessening the severity of fungal keratitis in a rabbit model and should be considered effective treatment alternatives in the therapy of Aspergillus fumigatus keratitis. On day 15 after, the topical and combine classes had statistically significant better effect compared to the oral groups, but no distinguished difference was observed between topical and combine groups, suggesting that topical itraconazole were effective in lessening the severity of fungal keratitis in a rabbit model and systemic administration is not necessary.