N Venkatesh Prajna1, Naveen Radhakrishnan1, Prajna Lalitha1, Ariana Austin2, Kathryn J Ray2, Jeremy D Keenan3, Travis C Porco4, Thomas M Lietman5, Jennifer Rose-Nussbaumer6. 1. Aravind Eye Hospital, Madurai, India. 2. Francis I. Proctor Foundation, University of California, San Francisco, San Francisco, California. 3. Francis I. Proctor Foundation, University of California, San Francisco, San Francisco, California; UCSF Department of Ophthalmology, University of California, San Francisco, San Francisco, California. 4. Francis I. Proctor Foundation, University of California, San Francisco, San Francisco, California; UCSF Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California. 5. Francis I. Proctor Foundation, University of California, San Francisco, San Francisco, California; UCSF Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California; UCSF Department of Ophthalmology, University of California, San Francisco, San Francisco, California. 6. Francis I. Proctor Foundation, University of California, San Francisco, San Francisco, California; UCSF Department of Ophthalmology, University of California, San Francisco, San Francisco, California; The Permanente Medical Group, Redwood City, California. Electronic address: jennifer.rose.nussbaumer@gmail.com.
Abstract
PURPOSE: To determine if there is a benefit to adjuvant corneal crosslinking (CXL) and to compare natamycin versus amphotericin B for filamentous fungal keratitis. DESIGN: Outcome-masked, 2×2 factorial design, randomized controlled clinical trial. PARTICIPANTS: Consecutive patients presenting with moderate vision loss from a smear-positive fungal ulcer at Aravind Eye Hospital, Madurai, India. METHODS: Study eyes were randomized to 1 of 4 treatment combinations using an adaptive randomization protocol. The treatment arms included (1) topical natamycin 5% alone, (2) topical natamycin 5% plus CXL, (3) topical amphotericin B 0.15% alone, and (4) topical amphotericin 0.15% plus CXL. MAIN OUTCOME MEASURES: The primary outcome of the trial was microbiological cure at 24 hours on repeat culture. Secondary outcomes included best spectacle-corrected visual acuity (BSCVA) at 3 weeks and 3 months, percentage of study participants with epithelial healing at 3 days, 3 weeks, and 3 months, infiltrate or scar size at 3 weeks and 3 months, 3-day smear and culture, and adverse events. RESULTS: Those randomized to CXL regardless of medication (topical natamycin or amphotericin) had 1.32-fold increased odds of 24-hour culture positivity, although this was not statistically significant (95% confidence interval [CI], 0.57-3.06; P = 0.51). We were also unable to find a difference in 24-hour culture positivity between those randomized to amphotericin and those randomized to natamycin when evaluating as a group regardless of whether or not they received CXL (coefficient 1.10; 95% CI, 0.47-2.54; P = 0.84). The BSCVA was approximately 0.22 logarithm of the minimum angle of resolution (logMAR) (2.2 Snellen lines) worse on average at 3 weeks among those receiving CXL regardless of medication (95% CI, -0.04 to 0.40; P = 0.04) and 0.32 logMAR (3.2 Snellen lines) worse visual acuity at 3 months after controlling for baseline visual acuity (95% CI, 0.03-0.54; P = 0.02). There was no difference in infiltrate or scar size, percentage of epithelialized or adverse events when comparing CXL with no CXL or the 2 topical medications. CONCLUSIONS: There appears to be no benefit of adjuvant CXL in the primary treatment of moderate filamentous fungal ulcers, and it may result in decreased visual acuity.
RCT Entities:
PURPOSE: To determine if there is a benefit to adjuvant corneal crosslinking (CXL) and to compare natamycin versus amphotericin B for filamentous fungal keratitis. DESIGN: Outcome-masked, 2×2 factorial design, randomized controlled clinical trial. PARTICIPANTS: Consecutive patients presenting with moderate vision loss from a smear-positive fungal ulcer at Aravind Eye Hospital, Madurai, India. METHODS: Study eyes were randomized to 1 of 4 treatment combinations using an adaptive randomization protocol. The treatment arms included (1) topical natamycin 5% alone, (2) topical natamycin 5% plus CXL, (3) topical amphotericin B 0.15% alone, and (4) topical amphotericin 0.15% plus CXL. MAIN OUTCOME MEASURES: The primary outcome of the trial was microbiological cure at 24 hours on repeat culture. Secondary outcomes included best spectacle-corrected visual acuity (BSCVA) at 3 weeks and 3 months, percentage of study participants with epithelial healing at 3 days, 3 weeks, and 3 months, infiltrate or scar size at 3 weeks and 3 months, 3-day smear and culture, and adverse events. RESULTS: Those randomized to CXL regardless of medication (topical natamycin or amphotericin) had 1.32-fold increased odds of 24-hour culture positivity, although this was not statistically significant (95% confidence interval [CI], 0.57-3.06; P = 0.51). We were also unable to find a difference in 24-hour culture positivity between those randomized to amphotericin and those randomized to natamycin when evaluating as a group regardless of whether or not they received CXL (coefficient 1.10; 95% CI, 0.47-2.54; P = 0.84). The BSCVA was approximately 0.22 logarithm of the minimum angle of resolution (logMAR) (2.2 Snellen lines) worse on average at 3 weeks among those receiving CXL regardless of medication (95% CI, -0.04 to 0.40; P = 0.04) and 0.32 logMAR (3.2 Snellen lines) worse visual acuity at 3 months after controlling for baseline visual acuity (95% CI, 0.03-0.54; P = 0.02). There was no difference in infiltrate or scar size, percentage of epithelialized or adverse events when comparing CXL with no CXL or the 2 topical medications. CONCLUSIONS: There appears to be no benefit of adjuvant CXL in the primary treatment of moderate filamentous fungal ulcers, and it may result in decreased visual acuity.
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