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    Cornea/External Disease

    This secondary analysis of the Mycotic Ulcer Treatment Trial (MUTT) II clinical trial explores the role of adjuvant oral voriconazole on clinical outcomes in Fusarium keratitis.


    MUTT II was a double-masked, placebo-controlled randomized clinical trial that included 240 patients with severe filamentous fungal keratitis and visual acuity of 20/400 or worse. Subjects were randomized to receive either oral voriconazole or placebo in addition to topical antifungal therapy. Both groups received topical voriconazole 1%, and after the results of the MUTT I became available, topical natamycin 5% was added.

    Study design

    The authors investigated the effect of adjuvant oral voriconazole on clinical outcomes specifically in patients with Fusarium corneal ulcers. Among 72 eligible participants, 33 were randomized to oral voriconazole and 39 to placebo.

    The primary outcome measure of the trial was the rate of corneal perforation or the need for therapeutic penetrating keratoplasty (PK). Secondary outcomes included rate of reepithelialization, BCVA, and infiltrate or scar size at 3 weeks and 3 months.


    After controlling for the depth of the initial infiltrate, patients randomized to oral voriconazole had a 0.43-fold decreased risk of perforation or therapeutic PK compared with placebo.

    Additionally, at 3 months, eyes treated with oral voriconazole-treated had significantly larger decreases in infiltrate and/or scar size (P<0.001) and a slight improvement in visual acuity from baseline that did not reach statistical significance (P=0.052).

    Rates of reepithelialization, however, were no better in the oral voriconazole group.


    All patients in this study were enrolled from India and Nepal, which is a significant limitation as organisms in this region might exhibit characteristics different from those found in other regions. Moreover, most of the infections in the study were related to agricultural exposure and not contact lens wear, which is the predominant cause of fungal keratitis in developed countries.

    Last, in an accompanying editorial,  Bennie Jeng, MD, notes that 6 individuals in the oral placebo group were using systemic antifungals at presentation compared with 2 in the oral voriconazole group. Prior studies have suggested that pretreatment with antifungal agents (including oral azoles) could be a risk factor for worse outcomes.

    Clinical significance

    This was a rigorous clinical trial that has provided useful information for a specific situation. While questions remain about the widescale application of the results, the findings still provide guidance on the use of available antifungal agents in the case of Fusarium keratitis.