Effect of pretreatment with antifungal agents on clinical outcomes in fungal keratitis

BackgroundTo determine if pretreatment with antifungal agents is predictive of worse clinical outcome in a fungal keratitis clinical trial.DesignNon-pre-specified subgroup analysis of a randomized controlled trial in a tertiary hospital.ParticipantsThree hundred twenty-three fungal ulcer cases with an enrolment visual acuity of 20/40 to 20/400.MethodsThe Mycotic Ulcer Treatment Trial I was a randomized, double-masked trial to determine the optimal treatment for filamentous fungal keratitis at the Aravind Eye Care System, India. Enrolled cases were randomized to receive topical natamycin or voriconazole. Prior antifungal medication use, dose and duration were collected at enrolment. A subgroup analysis was performed to determine if patients using natamycin or azoles at presentation have worse clinical outcomes compared with those who were not pretreated.Main outcome measuresThree-month visual acuity (primary), 3-month infiltrate or scar size, corneal perforation and/or transplant and re-epithelialization time.ResultsOf the 323 patients enrolled, 44% presented on an antifungal agent. Pretreated patients had larger mean baseline infiltrate size (P < 0.001) and epithelial defect size (P = 0.02). Multivariate regression analysis demonstrated that pretreatment was associated with significantly worse 3-month visual acuity (P = 0.006), larger 3-month scar size (P < 0.001) and increased odds of corneal perforation and/or transplant (P = 0.001).ConclusionsFungal keratitis that is smear-positive despite being pretreated with appropriate antifungal agents appears to be a risk factor for worse outcomes, likely a result of initial ulcer severity and treatment failure. These patients may benefit from more aggressive multimodal therapy at a tertiary centre