• Written By: Brianna Janocha; Damien M Luviano MD
    Cornea/External Disease, Refractive Mgmt/Intervention

    Review of: Cross-Linking–Assisted Infection Reduction

    Prajna N, Radhakrishnan N, Lalitha P, et al. Ophthalmology, February 2020

    This study evaluated adjuvant corneal crosslinking (CXL) for treatment of filamentous fungal keratitis.

    Study design

    This 2x2 factorial design, outcome-masked clinical trial included 403 patients presenting with moderate smear-positive filamentous fungal corneal ulcers at Aravind Eye Hospital in Madurai, India. Patients were randomized to topical natamycin 5%, natamycin plus CXL, topical amphotericin 0.15% or amphotericin plus CXL. They received medication every hour that they were awake in addition to homatropine 2% three times daily. Corneal scraping was performed upon enrollment and repeated at 24 hours as the primary measure of a successful microbiological cure. Participants were examined at 3 days, 3 weeks and 3 months to assess epithelial healing by their measured best-spectacle corrected visual acuity (BSCVA).


    Crosslinking was linked to an increased chance of having a positive 24-hour culture, regardless of medication type; however, this was not statistically significant. There were no statistical differences between the natamycin and amphotericin arms, regardless of CXL. Patients who received CXL, on average, had worse BSCVA than those who received only topical treatment. Scar size, infiltrate size, percentage of epithelialized tissue and frequency of adverse events were similar among all groups.


    Although these findings suggest there is no benefit to adjuvant CXL for filamentous fungal keratitis, the results might not represent the procedure’s potential therapeutic effects for corneal infections. All participants in this study were natives of India and the majority acquired infections from agricultural exposure. Since contact lens use is the primary cause of infections in other regions, the microorganisms in this study may possess unique characteristics and response patterns to treatment.

    Clinical significance

    At this time, there appears to be no benefit to adjuvant CXL for moderate filamentous fungal ulcers, although it may have a negative impact on visual acuity. The topical treatments natamycin and amphotericin produce similar outcomes, both successfully decreasing culture positive rate over time. Further studies should evaluate alternative CXL duration or timing, UV-C treatment as opposed to UV-A, and the use of a larger sample size for each type of fungal infection.