The Prognostic Value of Persistent Culture Positivity in Fungal Keratitis in the Mycotic Antimicrobial Localized Injection Trial.

PURPOSE: To evaluate the utility of repeat cultures at days 3 and 7 after starting antifungal medications for predicting outcomes in fungal keratitis. DESIGN: Pre-specified secondary analysis of the randomized clinical trial Mycotic Antimicrobial Localized Injection trial. METHODS: Patients presenting to Aravind Eye Hospital, Pondicherry with fungal keratitis and visual acuity worse than 20/70 received topical natamycin and were randomized to either receive intrastromal injection of voriconazole or topical therapy alone. All subjects received corneal cultures at date of presentation, day 3, and day 7. Outcome measures included 3-week and 3-month visual acuity and scar size, corneal perforation and/or the need for therapeutic penetrating keratoplasty (TPK). Visual acuity and scar size were analyzed with multiple linear regression controlling for baseline measures. Survival analysis was used to analyze the risk of corneal perforation and/or need for TPK. RESULTS: Of the 70 study subjects with fungal keratitis, 25/69 (36%) remained culture positive at day 3, and 20/62 (32%) were culture positive at day 7. Culture positivity at day 3 conferred a hazard ratio of 2.8 for requiring TPK (p=0.03), but was not a statistically significant predictor of perforation, scar size, or final visual acuity. Culture positivity at day 7 had a hazard ratio of 3.5 for requiring TPK (p=0.003). Those with positive cultures at day 7 had on average 3-LogMAR lines worse visual acuity at 3 months (95% CI 0.9 to 5.2-LogMAR lines, p=0.006) and 1.1 mm larger scar size at 3 months after controlling for baseline measures (95% CI 0.1 to 2.2 mm; p=0.03). CONCLUSIONS: While not as predictive as day 7 cultures, culture positivity at day 3 after starting treatment is a significant predictor of the need for TPK in patients with moderate to severe filamentous fungal keratitis. This has applications for risk stratification, and may facilitate earlier consideration of TPK in high-risk patients.