Therapeutic Penetrating Keratoplasty Button Cultures in The Mycotic Ulcer Treatment Trial II: A Randomized Trial Comparing Oral Voriconazole Versus Placebo

Abstract

Objective: To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis.

Design: Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial.

Methods: Study Participants: Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK).

Intervention: Study participants were randomized to oral voriconazole vs oral placebo; all received topical antifungal drops.

Main outcome measures: TPK button culture positivity.

Results: A total of 95 of 194 (49.5%) study participants enrolled at Madurai, Coimbatore, or Pondicherry, India eventuated to TPK in an average of 20.9 days (standard deviation 15.2 days, range 2-71 days). TPK button cultures were available for 67 of 95 (71%) of the TPKs performed and were positive for filamentous fungus in 45 of 67 (67%) cases. For each 1-day increase in the time to TPK there was 0.94-fold decreased odds of fungal culture positivity (95% confidence interval [CI] 0.90-0.98, P = .005). Those randomized to oral voriconazole had 1.26-fold increased odds of TPK button culture positivity after controlling for time to TPK and baseline organism, but this was not statistically significant (95% CI 0.32-4.87; P = .74). Those who underwent TPK for lack of response to medical therapy were 10.64-fold more likely to be culture positive than if the indication for surgery was perforation and this was statistically significant (95% CI 2.16-51.70; P = .003).

Conclusions: There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. Infection rather than inflammation appears to be the reason for the worsening clinical picture in many of these patients.