1. Copyright restrictions may apply JAMA Ophthalmology Journal Club Slides: Mycotic Ulcer Treatment Trial Prajna NV, Krishnan T, Mascarenhas J, et al; Mycotic Ulcer Treatment Trial Group. The Mycotic Ulcer Treatment Trial: a randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol. Published online December 10, 2012. doi:10.1001/jamaophthalmol.2013.1497.

2. Copyright restrictions may apply Introduction Infectious keratitis is a leading cause of monocular blindness globally, and fungal keratitis accounts for about 50% of all corneal ulcers. Fungal keratitis is more difficult to treat than bacterial corneal ulcers and often results in worse outcomes. Natamycin is the only US Food and Drug Administration–approved antifungal for topical ophthalmic use, but expert opinion and in vitro results indicate that voriconazole may be superior. Objective: –To compare topical natamycin vs topical voriconazole in the treatment of filamentous fungal keratitis.

3. Copyright restrictions may apply Study Design: Double-masked, multicenter, randomized controlled trial. Participants: 368 patients with smear-positive filamentous fungal keratitis and visual acuity between 20/40 and 20/400 (inclusive). Data Analysis: Best spectacle-corrected visual acuity (BSCVA) at 3 months analyzed in a multiple linear regression model with baseline BSCVA and treatment arm as covariates. Limitations: –Enrolled patients only from South India. –No contact lens wearers enrolled. –Compared only topical monotherapies. Methods

4. Copyright restrictions may apply Natamycin-treated cases had significantly better 3-month BSCVA than voriconazole-treated cases (P =.006) Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (P =.009). Fusarium cases fared better with natamycin than with voriconazole for 3-month BSCVA (P <.001) and perforation (P =.001). Non-Fusarium cases fared similarly for 3-month BSCVA (P =.81) and perforation (P =.86). Results

5. Copyright restrictions may apply Table title or figure legend with table or figure Results Multiple Linear Regression Predicting 3-Month BSCVA Covariate Coefficient, logMAR SE95% CIP Value Model with enrollment BSCVA and treatment arm Enrollment BSCVA0.720.080.56 to 0.89<.001 Natamycin vs voriconazole −0.180.06−0.30 to −0.05.006 Model with interaction for Fusarium species Enrollment BSCVA0.710.080.55 to 0.87<.001 Natamycin vs voriconazole Fusarium−0.410.11−0.61 to −0.20<.001 Non-Fusarium−0.020.08−0.17 to 0.13.81 Abbreviation: BSCVA, best spectacle-corrected visual acuity.

6. Copyright restrictions may apply Results Adverse Events by Treatment Arm Adverse EventVoriconazoleNatamycinTotalP Value Serious Corneal perforation151025.31 TPK291342.01 Corneal perforation and/or TPK341852.02 Endophthalmitis202.50 Death112>.99 Myocardial infarction or stroke101>.99 Nonserious >2-mm increase in hypopyon12517.09 >50% increase in infiltrate/scar size13518.06 Progressive corneal thinning to ≥50% of thickness at enrollment 202.25 Other nonserious336>.99 Abbreviation: TPK, therapeutic penetrating keratoplasty.

7. Copyright restrictions may apply Why voriconazole? –Recent survey of cornea specialists indicated that while natamycin was the most commonly used antifungal, voriconazole was largely preferred. –Isolates from fungal keratitis demonstrated good in vitro susceptibility to voriconazole. The Mycotic Ulcer Topical Treatment Trial I (MUTT I) found that natamycin- treated cases had significantly better clinical and microbiological outcomes compared with voriconazole-treated cases. –Much of the difference was attributable to improvements seen in Fusarium cases. Comment

8. Copyright restrictions may apply If you have questions, please contact the corresponding author: –Thomas M. Lietman, MD, Department of Ophthalmology, University of California, San Francisco, 513 Parnassus Ave, Box 0412, San Francisco, CA 94143-0412 (tom.lietman@ucsf.edu). Funding/Support This work was supported by grants U10 EY018573 (Dr Lietman) and K23 EY017897 (Dr Acharya) from the National Eye Institute and grants from That Man May See, the Harper/Inglis Trust, the South Asia Research Foundation, and Research to Prevent Blindness (Drs Lietman and Acharya). Natamycin and voriconazole were donated by Alcon and Pfizer, respectively. Conflict of Interest Disclosures None reported. Contact Information