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    CXL: Not for Fungal Keratitis?

    Cornea/External Disease

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    Some cornea specialists are already using corneal cross-linking (CXL) plus antifungal medica­tions to treat moderate filamentous fungal ulcers. But a recent study suggests that this strategy may be ineffective.1 Moreover, CXL in these patients may result in decreased visual acuity (VA).

    Although some evidence has suggested potential benefits of CXL for treating bacterial and fungal kerati­tis, “more robust evidence was necessary,” said Jennifer Rose-Nussbaumer, MD, at the University of California, San Francisco.

    As a result, she said, “We designed this trial to evaluate the benefit in fungal keratitis,” which can be particularly challenging to treat.

    Study design. The study was conducted at Aravind Eye Hospital in Madurai, India. Out of 403 patients with smear-positive ulcers, 111 were randomized to one of the following four treatments: 1) topical natamycin 5% alone, 2) topical natamycin plus CXL, 3) topical ampho­tericin B 0.15% alone, and 4) topical amphotericin plus CXL.

    The primary outcome of the trial was microbiologi­cal cure at 24 hours on repeat culture. Secondary out­comes included best spectacle-corrected VA (BSCVA) at three weeks and three months; percentage of study participants with epithelial healing at three days, three weeks, and three months; infiltrate or scar size at three weeks and three months; and adverse events.

    Outcomes. The researchers found no benefit to adju­vant CXL in the treatment of filamentous fungal ulcers. “Specifically, we found no improvement in microbiolog­ical cure including culture and smear, no improvement in infiltrate or scar size, no increase in the percentage epithelialized at three weeks or three months, and no difference in adverse events,” they stated. These results did not vary depending on whether patients received natamy­cin or amphoter­icin.

    Moreover, the results suggest that adjuvant CXL may have a negative effect on VA. At three weeks, BSCVA was approximately 2.2 Snellen lines worse among those receiving CXL; at three months, BSCVA in those receiving CXL was ap­proximately 3.2 Snellen lines worse. The reason for this is unclear, the researchers said.

    —Arthur Stone


    1 Prajna NV et al. Ophthalmology. 2020;127(2):159-166.


    Relevant financial disclosures—Dr. Rose-Nussbaumer: None.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Chen Research related to this study was funded by a career development award from Research to Pre­vent Blindness and by the NEI.

    Dr. Humayun Allergan: C,L; Duke Eye Center: P; Eyemedix: C,O,P,S; Iridex: P; Johns Hopkins University: P; Lu­tronic Vision: C,O; MTTR: C,O; Outlook Therapeutics: C; Regenerative Patch Technologies: C,O,P; Replenish: C,O,P; Santen: C,L; Second Sight Medical Products: O,P; USC: E,P.

    Dr. Morley None.

    Dr. Rose-Nussbaumer None.

    Disclosure Category



    Consultant/Advisor C Consultant fee, paid advisory boards, or fees for attending a meeting.
    Employee E Employed by a commercial company.
    Speakers bureau L Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
    Equity owner O Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
    Patents/Royalty P Patents and/or royalties for intellectual property.
    Grant support S Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.


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