Topical amphotericin B and subconjunctival injection of fluconazole (combination therapy) versus topical amphotericin B (monotherapy) in treatment of keratomycosis. Trial of chlorhexidine gluconate for fungal corneal ulcers. Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh. A randomised clinical trial comparing 2% econazole and 5% natamycin for the treatment of fungal keratitis. Efficacy of topical and systemic itraconazole as a broad-spectrum antifungal agent in mycotic corneal ulcer. A preliminary study. Topical silver sulphadiazine--a new drug for ocular keratomycosis. Comparison of natamycin and voriconazole for the treatment of fungal keratitis. Silver sulphadiazine in the treatment of mycotic keratitis. Voriconazole versus natamycin as primary treatment in fungal corneal ulcers.
The aim of the study was to compare the use of combination therapy of topical amphotericin B (0.5 mg/mL) eye drops together with subconjunctival injection of fluconazole (2 mg/mL) with the use of topical amphotericin B (0.5 mg/mL) eye drops alone in dealing with cases of fungal keratitis.
                The study was performed in the Ophthalmology Department, Zagazig University and included 48 eyes of 48 patients who presented clinically with fungal keratitis. Laboratory investigations were performed, including direct microscopy of corneal smear using gram staining and culture of corneal specimens using Saboraud agar media and bacterial agar media. According to laboratory results, cases were classified into 2 groups: group 1 comprising 24 eyes treated by a combination therapy of topical amphotericin B eye drops (0.5 mg/mL) with subconjunctival injection of fluconazole (2 mg/mL) and group 2 comprising 24 eyes treated by topical amphotericin B eye drops (0.5 mg/mL) alone.
                Direct corneal smear for all 48 eyes included in the study revealed 18 eyes (38%) with positive fungal spores, 3 of them (6%) with gram-positive bacterial infection. Fungal culture of corneal specimens revealed positive result in 36 eyes (75%), including the positive corneal smear cases showing Candida in 12 eyes and filamentous fungi in 24 eyes. Treatment by a combination therapy in group 1 revealed statistically significant result (P < 0.05) of healing of corneal ulcers in 20 eyes (83%), with a mean duration of healing of 31 days (standard deviation [SD] +/-3), in comparison to group 2 with monotherapy, which revealed 16 eyes (67%), with a mean duration of healing of 37 days (SD +/-2).
                Combination therapy of topical amphotericin B eye drops with subconjunctival injection of fluconazole was more efficient (according to the percentage and the duration of healing of the ulcers) than the use of topical amphotericin B eye drops alone in dealing with cases of fungal keratitis--it may be contributed to the broad spectrum of the antifungal agents of the combination therapy than the monotherapy. Suppurative corneal ulcers due to filamentous fungi are a serious and intractable problem in many tropical developing countries. In vitro studies and a small pilot study have shown that chlorhexidine gluconate is effective. The aim was to establish the optimum concentration which would be appropriate to use in a larger randomized clinical trial.
                A masked randomized clinical trial of three concentrations of chlorhexidine compared with natamycin 5% was carried out in consecutive patients with established corneal ulcers shown by microscopy to contain fungal hyphae and later proven to be culture positive. Topical treatments were applied 1/2-hourly to 2-hourly for up to 5 days, with reduced frequency thereafter, and all patients were re-assessed at 21 days.
                Of 60 patients entered in the trial, 2 were lost to follow-up, and 12 were classified as 'severe' with little prospect of recovery. At 5 days the response was related to the concentration of chlorhexidine, with 0.2% giving the best results. Compared with the response to natamycin as the referent, the relative efficacy was 1.17 with chlorhexidine 0.05%, 1.43 with 0.1%, and 2.00 with 0.2%. The superiority of 0.2% chlorhexidine over natamycin was statistically significant (relative efficacy 2.20, p = 0.043) in patients not having had prior antifungal treatment.
                This preliminary study justifies further trials of chlorhexidine as a primary treatment for fungal corneal ulcers in circumstances where specific antifungal agents are not available. The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries. The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis.
                Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy. They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5%. The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals. The outcome measures were healing at 21 days and presence or absence of toxicity. If there was not a favourable response at 5 days, "treatment failure" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial.
                71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin. One allocated to natamycin grew bacteria and therefore was excluded from the analysis. None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days. Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04). If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers. Equal numbers of Aspergillus (22) and Fusarium (22) were grown. The Aspergillus were the most resistant to either primary treatment.
                Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available. To compare 2% econazole and 5% natamycin in the management of fungal keratitis.
                A randomised clinical trial was performed using 2% econazole or 5% natamycin as the two treatment arms on patients presenting with culture positive fungal keratitis to the cornea service at Aravind Eye Care System, Madurai, India.
                116 patients were recruited, and 112 continued in the study. There were no significant differences between the two arms at baseline or for success (defined as a healed or healing ulcer) at final visit (p = 0.79).
                2% Econazole appears to be as effective as 5% natamycin for the management of fungal keratitis. To evaluate the efficacy of topical (1%) and systemic itraconazole against common fungi such as Aspergillus and other filamentous fungi that cause mycotic corneal ulcer.
                A prospective randomised, controlled study was done in 54 clinically suspected cases of fungal keratitis of which 44 were culture proven. Half the cases (n=27) with superficial involvement were treated with only topical itraconazole (1%) and the other half were treated with both topical and systemic itraconazole.
                Aspergillus, Penicillium and Fusarium were the most common fungi isolated. The ulcer resolved in 42 eyes (77%) and 12 eyes (23%) did not respond well to treatment. Four of 12 non-responding eyes were caused by Fusarium species.
                Itraconazole, given either topically or systemically, is effective in treating mycotic corneal ulcers. The efficacy of silver sulphadiazine in human keratomycosis has not been evaluated so far. Encouraged by the success of an earlier experimental trial, a prospective, controlled, randomised double masked clinical study was designed to evaluate the efficacy of 1% silver sulphadiazine ophthalmic ointment in 20 eyes of mycotic keratitis. Miconazole 1% was used for comparative evaluation in another 20 eyes. Silver sulphadiazine had a higher success rate (80% vs 55%) than miconazole. It had broad antifungal activity and was found to be effective in fusarium keratitis. Absence of side effects, economy, and its efficacy in deeper and extensive lesions were additional advantages. It is concluded from this study that silver sulphadiazine is a safe and effective broad spectrum antifungal agent which can be used for the treatment of human keratomycosis. To conduct a therapeutic exploratory clinical trial comparing clinical outcomes of treatment with topical natamycin vs topical voriconazole for fungal keratitis.
                The multicenter, double-masked, clinical trial included 120 patients with fungal keratitis at Aravind Eye Hospital in India who were randomized to receive either topical natamycin or topical voriconazole and either had repeated scraping of the epithelium or not.
                The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months. Other outcomes included scar size, perforations, and a subanalysis of BSCVA at 3 months in patients with an enrollment visual acuity of 20/40 to 20/400.
                Compared with those who received natamycin, voriconazole-treated patients had an approximately 1-line improvement in BSCVA at 3 months after adjusting for scraping in a multivariate regression model but the difference was not statistically significant (P = .29). Scar size at 3 months was slightly greater with voriconazole after adjusting for scraping (P = .48). Corneal perforations in the voriconazole group (10 of 60 patients) were not significantly different than in the natamycin-treated group (9 of 60 patients) (P >.99). Scraping was associated with worse BSCVA at 3 months after adjusting for drug (P = .06). Patients with baseline BSCVA of 20/40 to 20/400 showed a trend toward a 2-line improvement in visual acuity with voriconazole (P = .07).
                Overall, there were no significant differences in visual acuity, scar size, and perforations between voriconazole- and natamycin-treated patients. There was a trend toward scraping being associated with worse outcomes. Application to Clinical Practice The benefit seen with voriconazole in the subgroup of patients with baseline visual acuity of 20/40 to 20/400 needs to be validated in a confirmatory clinical trial. Trial Registration clinicaltrials.gov Identifier: NCT00557362. nan To evaluate the efficacy of topical 1% voriconazole versus 5% natamycin in treatment of fungal corneal ulcers.
                A prospective, randomized pilot study in a tertiary care hospital.
                Thirty patients of microbiologically proven fungal keratitis divided randomly in two groups of 15 patients each.
                Two groups were treated with either 5% natamycin (group A) or 1% voriconazole (group B) topically as a primary treatment for fungal keratitis. The mean size, depth of infiltrate and LogMAR visual acuity at presentation were comparable in both groups (P > 0.05). Patients were followed up for minimum of 10 weeks or till complete resolution of ulcer, whichever was later. Cultures to identify the causative organisms were performed.
                Time of resolution of the ulcer.
                Twenty-nine of the total 30 patients showed complete resolution. Average time of resolution and gain in LogMAR visual acuity was 24.3 days and 1.12 in group A and 27.2 days and 0.77 in group B. These were comparable in the two groups (P > 0.05%). Aspergillus spp. (40%) and Curvularia spp. (30.0%) were found to be most common isolates.
                Topical 1% voriconazole was found to be safe and effective drug in primary management of fungal keratitis, its efficacy matching conventional natamycin. There was no added advantage of using topical 1% voriconazole over topical natamycin as primary treatment in fungal keratitis.
                © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.
Based on the trials included in this review, there is no evidence to date that any particular drug, or combination of drugs, is more effective in the management of fungal keratitis. The trials included in this review were of variable quality and were generally underpowered.