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Abstract Fungal keratitis is a serious ocular problem that causes devastating corneal damage d blindness worldwide. Trauma associated with contamination by vegetative material, aring contact lens, corneal surgeries and long term corticosteroid use are common risk tors. In developed countries, trauma associated with contamination by vegetative material the main cause of fungal keratitis. The most common causative fungi are Candida albicans . albicans), Aspergillus species and Fusarium solani (F. Solani). There are three main classes of drugs available for use In fungal eye infections: lyenes, azoles and 5-fluorocytosine. Available effective drugs are essentially limited. These tablished agents suffer from a number of limitations that can render their use difficult. ese limitations include dose-limiting nephrotoxicity associated with amphotericin Band pid development of resistance with flucytosine and azoles. Accordingly, there is an urgent eed for new antifungals with a broad,’ fungicidal spectrum of action, suitable dosage form, wer dose-limiting side effects and good corneal penetration. Eugenol is the active component of clove (Syzigium aromaticum), It is documented as timicrobial drug against different strains of bacteria and fungi. The aim of this study was to ’nd a suitable antifungal natural product for treatment of induced C. albicans and to evaluate e effect of eugenol on induced C. albicans-induced keratitis in New Zealand albino rabbits. To find out the suitable antifungal natural products, five plants containing volatile oils s the main constituents underwent water distillation to extract the volatile oil content of each. All the extracted oils were tested for their in vitro antifungal activity against C. albicans, A. niger and F. solani, and the data proved that clove oil had the lowest MIC (1 mg/ml) against C. albicans, A. niger and (1.5 mg/ml against) F. solani followed by cumin and caraway (3 mg/ml) against C. albicans, A. niger and (1.5 mg/ml) against F. solani then basil (6 mg/ml) against C. albicans, (3 mg/ml) against A. niger and and (1.5 mg/ml) against F. Summary, Conclusion, and Recommendations solani and marjoram (6 mg/ml) against the three mentioned orgamsms. This data was amazing when compared with the MIC of fluconazole which was used as control (MIC> 400 Ilg/ml). Mixtures of clove, cumin and caraway essential oils were tested for their in vitro antifungal activity and showed synergistic effect. However, clove oil alone showed the best activity. Antifungal activity of the major components of clove, cumin and caraway oils (eugenol, cuminaldehyde and carvone, respectively) was tested and the data confirmed that eugenol had the best antifungal activity (MIC= 2mg/ml) against C. albicans and (O.5mg/ml) against A. niger. Mixtures of eugenol, cuminaldehyde and carvone were tested for synergistic effect and according to the MICs of all; we can conclude that there is no synergism between the main components which drew our thoughts to choose eugenol for testing on C. albicanssinduced keratitis. To evaluate the effect of eugenol in treating C. albicans-induced keratitis, we examined the toxicity and the penetration of eugenol on corneal tissues. For toxicity study, eugenol was applied as eye drops (eugenol dissolved in PG) to 54 New Zealand rabbit eyes. The doses used were 256, 128,64, 32, 16, 8,4,2 and 1 mg/ml. Another six eyes were used as control (received PG eye drops). We found that the 4 mg/ml dose was the maximum nontoxic dose. The penetration of eugenol inside the eye was investigated by HPLC analysis in two steps. The first step was to analyze samples of aqueous humor and the results was negative for small concentrations (no detection of eugenol inside the samples for 4, 2 and I mg/ml). The second step was analysis of samples of corneal tissue supernatant using eugenol eye drops (4 mg/ml) as a preliminary test and the analysis confirmed that eugenol had been detected in the corneal tissue supernatant when used with that dose. mmary, Conclusion, and Recommendations To evaluate the effect of eugenol eye drops on a rabbit model of C. albicans-induced atitis, 3 groups of rabbit’s eyes were used and were divided as follows: Group 1 (control group): 12 rabbit eyes received saline eye drops every hour for 15 s immediately after intrastromal inoculation of the fungus. By the end of the period (15 s), there were six eyes (50%) that had very large corneal lesions, five eyes (42%) that had ophthalmitis and one eye (8%) that had a healed scar. Group 2: 12 rabbit eyes had immediate treatment with eugenol eye drops every hour 15 days started after 1 hour of intrastromal inoculation of the fungus. By the end of the tment period, seven eyes (58%) showed clear cornea, two eyes (17%) had healed scar and e eyes (25%) had severe lesions. Group 3: 16 rabbit eyes had treatment with eugenol eye drops at the fourth day of the stromal inoculation of the fungus every hour for 15 days. By the end of the treatment ’od, five eyes (31.3%) showed clear cornea, seven eyes (43.7%) had healed scar and three s(19%) had localized lesion that started healing and one eye (6%) had endophthalmitis. This study shows promising data of topical eugenol in the treatment of C. albicanssced keratitis in non-human primates either after immediate or delayed treatment. Treatment with eugenol eye drops for 15 days was successful in at least 75% of |