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    Eyedrops Change Surface Microbiota

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    Benzalkonium chloride (BAK) is the most frequently found preservative in eyedrops. Now researchers report a possible link between preservatives, which are intended to prevent growth of pathogenic bacteria in medication bottles, and microbial changes that may put the ocular surface at greater risk for inflammation.1

    For this study, the researchers evaluated the impact of topical glaucoma medications. “We found that glaucoma patients taking IOP-lowering drops [with preservatives] had an altered ocular surface microbiome compared to age-matched subjects without a history of glaucoma or use of eyedrops,” said Bryan J. Winn, MD, at the University of California, San Francisco. “These glaucoma patients had fewer of the normal commensal bacteria that we think are important for maintaining ocular surface homeostasis.”

    Microbial changes found on ocular surface of patients who use glaucoma drops, including greater presence of Bifidobacterium.

    MICROBIAL COMPOSITION. Treated eyes had a highly diverse array of microbes on their ocular surface, including Bifidobacterium.

    Comparing three groups. For this study, the researchers conducted ribosomal RNA sequencing on ocular surface swabs collected from both eyes of 17 participants. Ten patients had asymmetric/unilateral glaucoma and were being treated with a variety of topical eyedrops containing BAK on one eye. Seven age-matched healthy controls had no history of ocular disease or eyedrop use.

    The samples were categorized into three groups: 1) patients’ glaucomatous eyes treated with eyedrops (n = 10), 2) a control group of the patients’ contralateral untreated eyes (n = 10), and 3) a secondary control group of healthy eyes (n = 14). The researchers compared microbial diversity and composition, with differences tested for association with ocular surface disease measures.

    Effect on the microbiota. The microbial composition of treated eyes was distinct from that found in healthy controls. Specifically, treated eyes had a highly diverse array of bacteria that was significantly different from the less diverse microbes found on the eyes of healthy controls.

    In an unexpected finding, ocular surface changes occurred in both treated and contralateral untreated glaucomatous eyes. This may indicate that the ocular surface microbiome is a “bilateral microbial niche,” Dr. Winn said. In other words, changes or perturbations that occur in one eye may have bilateral effects.

    Other findings. In other findings, treated eyes were found to have decreased tear meniscus height and tear break-up time. In addition, results of genome inference analysis suggested that the ocular surface microbes of treated eyes had a greater capacity for inducing inflammation than those of healthy controls.

    Is BAK to blame? Patients were treated with a variety of eyedrop formulations, yet all eyes exhibited similar changes to the ocular microbiome. In addition, neither the duration nor the frequency of glaucoma therapy was associated with differences in ocular bacterial diversity or microbiome composition. “These findings suggest that an ingredient common to all drops, and not the active medication ingredient, may be responsible for inducing the changes to the microbiota,” Dr. Winn said.

    Follow-up study. Are the findings relevant to other drops with preservatives, such as those recommended for dry eye? “That is one of our concerns and is an avenue we are investigating,” Dr. Winn said. “The greatest number of drops used, including those available over the counter, are for the treatment of dry eye. If preservatives disturb ocular surface homeostasis via microbiome alterations, it may lend even more support for using nonpreserved alternatives.”

    Dr. Winn added, “We think the most plausible explanation for our findings is that a constant application of a detergent-like preservative to the ocular surface alters the ocular surface microbiome, but prospective studies are needed to confirm this.”

    —Miriam Karmel


    1 Chang CJ et al. Invest Ophthalmol Vis Sci. 2022;23(9):32.


    Relevant financial disclosures: Dr. Winn—Columbia University: P.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Aggarwal None.

    Dr. Al-Aswad AI Optics: C; Alcon: C; Bausch + Lomb: C; EnVision Health Technologies: EE; GlobeChek: PS; Mother Cabrini Health Foundation: S; New World Medical: S; Research to Prevent Blindness: S; Russell Berrie Foundation: S; Save Vision Foun­dation: C,S; Topcon: C,S; Virtual Field: C; Visi Health Technol­ogies: EE; World Care Clinical: C.

    Dr. Do Allergan/AbbVie: C,L; Alimera Life Sciences: C,L; Apellis: L; Bausch + Lomb: C,L; EyePoint: C,L.

    Dr. Winn Columbia University: P.

    Disclosure Category



    Consultant/Advisor C Consultant fee, paid advisory boards, or fees for attending a meeting.
    Employee E Hired to work for compensation or received a W2 from a company.
    Employee, executive role EE Hired to work in an executive role for compensation or received a W2 from a company.
    Owner of company EO Ownership or controlling interest in a company, other than stock.
    Independent contractor I Contracted work, including contracted research.
    Lecture fees/Speakers bureau L Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
    Patents/Royalty P Beneficiary of patents and/or royalties for intellectual property.
    Equity/Stock/Stock options holder, private corporation PS Equity ownership, stock and/or stock options in privately owned firms, excluding mutual funds.
    Grant support S Grant support or other financial support from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and\or pharmaceutical companies. Research funding should be disclosed by the principal or named investigator even if your institution receives the grant and manages the funds.
    Stock options, public or private corporation SO Stock options in a public or private company.
    Equity/Stock holder, public corporation US Equity ownership or stock in publicly traded firms, excluding mutual funds (listed on the stock exchange).


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