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Cross-linking Assisted Infection Reduction: A Randomized Clinical Trial (CLAIR)

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Abstract Number: 2222

AuthorBlock: Jennifer Rose-Nussbaumer1,2, Ariana Austin1, Travis C. Porco1, Venkatesh Prajna3, R Naveen3
1Ophthalmology, University of California San Francisco, San Francisco, California, United States; 2Ophthalmology, The Permanente Medical Group, Redwood City, California, United States; 3Aravind Eye Hospital, , India;

DisclosureBlock: Jennifer Rose-Nussbaumer, None; Ariana Austin, None; Travis C. Porco, None; Venkatesh Prajna, None; R Naveen, None;

Purpose
Filamentous fungal keratitis is a challenging disease with poor prognosis. In this randomized clinical trial we compare the efficacy of two commonly used topical antifungal medications, natamycin and amphotericin as well as the effect of adjuvant corneal cross-linking (CXL).

Methods
In this prospective, 2 x 2 factorial design, randomized, outcome-masked clinical trial, study participants presenting with smear positive filamentous fungal ulcers and visual acuity worse than 20/70 were enrolled at Aravind Eye Hospital in Madurai India. Using an adaptive randomization allocation study participants were assigned to 1 of 4 possible treatment arms: 1) natamycin only; 2) natamycin + CXL; 3) amphotericin only; 4) amphotericin + CXL in a 2 x 2 factorial design trial. The primary outcome was culture taken 24 hours after initiating treatment, secondary outcomes included visual acuity, scar size and complication rates including perforation and rate of therapeutic penetrating keratoplasty.

Results
111 patients were enrolled between January 2016 and March 2018. Table 1 outlines the baseline characteristics which were similar across the 4 treatment groups. There were small differences in culture status (culture positivity rate: natamycin only, 68%; natamycin + CXL, 81%; amphotericin only, 90%; amphotericin + CXL, 78%) and visual acuity (median [IQR], in logMAR: natamycin only, 1.05 [0.62, 1.12]; natamycin + CXL, 1.10 [0.60, 1.70]; amphotericin only, 1.05 [0.62, 1.70]; amphotericin + CXL, 1.22 [0.91, 1.70]). Culture positive ulcers were mostly Fusarium species (52%), Aspergillus (16%), and Curvularias (8%).

Amphotericin had similar efficacy compared with Natamycin with regard to repeat culture positivity, visual acuity, scar size and complication rates (Figure 1). We found no benefit of CXL on 24 hour repeat culture result. Those randomized to CXL had decreased visual acuity at 3 months compared with medical therapy (regression model of 3-month visual acuity by treatment arm, accounting for baseline visual acuity and comparing each arm to natamycin only: natamycin + CXL, coef. 0.42 [p = 0.03]; amphotericin only, coef. 0.10 [p = 0.59]; amphotericin + CXL, coef. 0.25 [p = 0.19]).

Conclusions
Amphotericin has similar efficacy compared to Natamycin for the treatment of filamentous fungal keratitis. There is no benefit to adjuvant CXL for the treatment of moderate fungal keratitis.

Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details.