Researchers assessed the efficacy of oral voriconazole for treating filamentous fungal keratitis.
Study design
This is a non-prespecified secondary analysis of the MUTT II trial, which was a double-masked, placebo-controlled randomized clinical trial with 240 patients. All patients had smear-positive filamentous fungal corneal ulcers and visual acuity of 20/400 or worse. During this trial, voriconazole did not reduce risk of perforation or need for therapeutic penetrating keratoplasty (TPK).
Of the 95 eyes that underwent therapeutic penetrating keratoplasty (TPK), 67 had button cultures at time of surgery. All patients received topical antifungal drops and were then randomized to receive an additional weight-based dose of oral voriconazole or oral placebo. The TPK button culture results were analyzed, with time to TPK and baseline culture results considered as co-variates.
Outcomes
Forty-five of the 67 cases were positive for filamentous fungus; 24 grew Fusarium, 11 grew Aspergillus, 10 had other fungi, 2 had Pseudomonas aeruginosa and 20 had no growth. TPK button cultures were unavailable for 6 of the 15 ulcers that were culture negative at baseline. The odds of fungal culture positivity reduced 0.94-fold per 1-day increase in time to TPK (P=0.005).
Although the oral voriconazole cohort was 1.26-fold more likely to have TPK culture positivity, the odds were not statistically significant. There was no significant difference in any of the species subgroups. However, TPKs performed for perforation were less likely to be culture positive than those performed due to lack of response to medical therapy (39% vs. 82%).
Limitations
Since the study was a non-prespecified analysis, some measurements (e.g., TPK button cultures) were not performed consistently. In addition, findings regarding this population of severe ulcers may not translate to other settings, such as contact lens wear. The authors did not confirm weight-based voriconazole dosing by serum trough levels and therefore may not have administered adequate levels to achieve drug efficiency.
Clinical significance
The authors provide further evidence that adjunctive oral voriconazole offers no additional benefits to topical therapy for treating corneal fungal ulcers. Ulcers that do not respond to medical therapy often progress due to active infection rather than prolonged inflammation alone. Further studies are therefore necessary to evaluate adjunct therapies in these advanced infectious cases.