A clinical trial conducted in India has reported that adjunctive topical voriconazole did not significantly improve clinical outcomes compared with natamycin 5% monotherapy. Di Zazzo and colleagues compared complete ulcer resolution with medical therapy and time to epithelial healing amongst 108 adults randomised 1:1 to receive either natamycin 5% plus voriconazole 1% (combination therapy) or natamycin 5% plus placebo (monotherapy).
Of the 108, 94 completed follow-up; 79.2% of participants in the combination group had complete healing, compared with 76.1% in the monotherapy group (p = 0.7). The median time to epithelial healing was 38 days for combination therapy and 39 days for monotherapy (p=0.86). Better visual outcomes (p=0.048) and lower rates of corneal perforation were documented for non-Aspergillus (Fusarium) cases using natamycin monotherapy.
Although voriconazole achieves higher intraocular concentrations and deeper stromal distribution compared with natamycin, the findings of this randomised trial yet affirm natamycin 5% monotherapy given hourly is an effective and well-tolerated first-line therapy for fungal keratitis, including cases caused by Fusarium species. Moreover, Fusarium species have been shown to exhibit intrinsic resistance to many azoles, including voriconazole. Conclusively, as previously reported in studies by Narayana et al., Sharma et al., and Prajna et al., combining voriconazole (topical and systemic) has no benefit in the treatment of fungal keratitis.
Image courtesy: Professor David Denning