A New Combination Formula for Treatment of Fungal Keratitis: An Experimental Study

Abstract

Objective. To formulate and evaluate slow release ketoconazole and ketorolac to treat fungal keratitis and associated inflammation. Methods. Experimental study with the following outcome measures. Pharmaceutical Evaluation. Mucoadhesive gels containing ketoconazole and ketorolac were used. Microbiological in vitro evaluation was performed using cup method. In vivo evaluation was performed on 24 rabbits divided into 2 groups, 12 rabbits each, group A (fast release formula; 6 times daily) and group B (slow release formula; 3 times daily). Each group was divided into two subgroups (6 rabbits each). Both eyes of rabbits were inoculated with Candida albicans. The left eye of all rabbits received the combination formulae. The right eye for one subgroup received ketoconazole as control 1 while the other subgroup received placebo as control 2. Clinical follow-up was done and, finally, the corneas were used for microbiological and pathological evaluation. Results. Gels containing high polymer concentration showed both high viscosity and mucoadhesion properties with slower drug release. The infected eyes treated with slow release formula containing both drugs showed better curing of the cornea and pathologically less inflammation than eyes treated with fast release formula. Conclusion. Slow release formula containing ketoconazole and ketorolac showed higher activity than fast release formula against fungal keratitis and associated inflammation.

Keratomycosis in a pet rabbit (Oryctolagus cuniculus) treated with topical 1% terbinafine ointment

“…The inoculation procedure used was superficial keratectomy followed by stromal injection of a spore suspension of a fungal strain, isolated from human samples . Clinical manifestations of induced keratomycosis include deep stromal infiltrate, surrounding stromal edema, and inflammation . The corneal lesions in the present rabbit resembled those of equine keratomycosis.…”

“…Keratomycoses have been induced experimentally in the rabbit with Candida albicans, Aspergillus fumigatus, and Fusarium solani, as part of safety and efficacy testing of various antifungal agents. The inoculation procedure used was superficial keratectomy followed by stromal injection of a spore suspension of a fungal strain, isolated from human samples . Clinical manifestations of induced keratomycosis include deep stromal infiltrate, surrounding stromal edema, and inflammation .…”

Conjunctival bacterial and fungal flora and cutaneous fungal flora in healthy domestic rabbits (Oryctolagus cuniculus)

“…Various reports described fungal keratitis induced experimentally in the rabbit as part of safety and efficacy testing of various antifungal agents (Lourdes Garcia et al 2002, Goldblum et al 2005, Yavas et al 2008, El -Mofty et al 2014. In contrast to other species, spontaneously occurring keratomycosis has only been reported once in a pet rabbit; fungal culture identified the pathogen as Aspergillus fumigatus (Bourguet et al 2016).…”

Reduced administration frequency for the treatment of fungal keratitis: a sustained natamycin release from a micellar solution

“…Afterwards, these plates were incubated for 24 hours at 37℃, and the inhibition zone was measured using a Vernier caliper. CFU/ml of C. albicans was circularly injected into the superficial stroma of rabbit eyes [29], [30]. Antibiotics (tobramycin and dexamethasone eye ointment, and levofloxacin eye drops) were administered to the eyes after surgery for three times a day for 15 days, in order to prevent bacterial growth.…”