Evaluation of topical 1% posaconazole therapy in refractory fungal keratitis

Purpose: The primary objective was to evaluate the clinical response of refractory cases of fungal keratitis to topical 1% posaconazole therapy.

Methods: Prospective longitudinal non-randomized open label dual-cohort study of 70 eyes of refractory fungal keratitis, 35 were recruited as posaconazole treatment (PCZ) group for topical 1% posaconazole therapy and compared to 35 eyes on conventional antifungal therapy. Study parameters included demographic and treatment details, visual acuity, comprehensive slit-lamp biomicroscopy, clinical photography, ASOCT at recruitment and weekly (week 1, 2, 3 and 4 after treatment initiation). Clinical assessment included keratitis severity grade, time of healing, and healing response. Anti-fungal susceptibility testing was performed.

Results: The mean age of 35 patients recruited in the PCZ treatment group was 45 ± 17.32 years and that for the conventional treatment group was 43.22 ± 15.04 years. Culture isolation was possible in 25 eyes (71.4%) in the PCZ treatment group, with Fusarium and Aspergillus spp. being the most common cornea pathogenic mycotic organisms. The mean healing time in the PCZ group was 27.13 ± 5.8 days and in the conventional treatment group was 26.41 ± 4.81 days. Healing response in the PCZ treatment showed that 27 eyes (77.14%) had healed, 3 (8.5%) had delayed healing, and 5 (14.28%) required therapeutic keratoplasty, whereas in the conventional treatment group, 26 (74.28%) healed, 2 (5.7%) had delayed healing, and 7 (20%) needed keratoplasty (P = 0.65, 0.72, 0.54, respectively). Topical 1% PCZ therapy of chronic mycotic keratitis was helpful in resolution in 85.7% of cases (30 eyes) with five eyes needing surgical intervention, which was comparable to that of conventional antimycotic therapy cohorts. Fusarium isolates showed greater susceptibility to natamycin in our study per MIC50 values, with susceptibility to the common antimycotic agents varying between the Aspergillus spp. in both PCZ treatment and conventional treatment groups. All isolates showed minimal values of MIC-50 with PCZ. Antifungal susceptibility testing in our study recruits showed that about 90% of the Fusarium spp. isolates to be best responsive to natamycin and PCZ, whereas Aspergillus niger isolates were sensitive to voriconazole, itraconazole, amphotericin B, and PCZ, Aspergillus flavus to voriconazole and PCZ, Aspergillus fumigatus to both polyenes and triazoles. Cladosporium spp. were best sensitive to natamycin and PCZ, Penicillium spp. to natamycin and azoles. Alternaria keratitis isolates were sensitive to voriconazole and PCZ, whereas Rhizopus isolate was best sensitive to PCZ.

Conclusion: Topical 1% PCZ therapy in refractory fungal keratitis was comparable to that of conventional antimycotic agents, with lower MIC-50 against the common pathogenic fungi as compared to natamycin, amphotericin B, and voriconazole.