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    BAK linked to ocular surface damage in animal studies

    Today's drugs better able to get into eye even if cell-cell adhesions intact


    Dr. Kahook
    Taormina, Sicily—Findings from two studies in an animal model indicate that medications preserved with benzalkonium chloride (BAK) may lead to loss of goblet cells as well as loss of cell-cell adhesions, which can predispose patients to having ocular surface damage. Once-daily dosing of latanoprost with 0.02% BAK (Xalatan, Pfizer) produced more goblet cell loss compared with either a preservative-free artificial tear or a travoprost ophthalmic solution (Travatan Z, Alcon Laboratories) preserved with an ionic-buffered preservative system (sofZia, Alcon Laboratories), said Malik Kahook, MD, presenting at the Fifth International Conference on the Tear Film and Ocular Surface: Basic Science and Clinical Relevance.

    Dr. Kahook, assistant professor, University of Colorado Denver, discussed the findings of two studies that he and Robert J. Noecker, MD, MBA, performed to investigate the effect on the ocular surface of rabbits of travoprost preserved with the ionic-buffered preservative system compared with latanoprost preserved with 0.02% BAK. They analyzed changes in conjunctival goblet cells and corneal epithelial desmosomes after exposure to the drops.

    "Part of the problem with using BAK as a preservative in glaucoma medications is the toxic effect that builds up over time," Dr. Kahook said. "It is not just the initial use of the preserved drop; it is the cumulative effect.

    "BAK specifically is what we call a detergent preservative as compared with others that are oxidizing preservatives and have a different effect on the ocular surface," he continued. "We have known for years that BAK has an effect on the ocular surface that consists of loss of goblet cells and breakdown of cell-cell connections. Being a detergent preservative, BAK breaks down the cell walls and causes cell death. Oxidizing preservatives do not cause cell death in human cells because we have the power to overcome the oxidizing effect."

    First study

    In the first study, 15 New Zealand white rabbits randomly were assigned into groups of five and were treated with once-daily topical application of travoprost, latanoprost, or preservative-free artificial tears. This dosing was chosen to mimic the clinical dosing of prostaglandin analogues in humans, Dr. Kahook said.

    The rabbits were treated for 30 days, at which time the investigators harvested conjunctiva and performed histologic analysis using mucin stains to count the number of goblet cells on the conjunctival surface.

    Investigators found a statistically significant difference between latanoprost with BAK and travoprost with the ionic-buffered preservative system. The mean number of goblet cells per high-power field was 2.21 ( 0.40) in the latanoprost with BAK group, 6.02 ( 1.20) in the travoprost with ionic-buffered preservative group, and 7.03 ( 1.33) in the preservative-free artificial tear group.

    "The number of goblet cells in the latanoprost with BAK group was significantly lower than the other two groups [p = 0.0001]," Dr. Kahook said.

    The difference in goblet cell numbers between the travoprost with ionic-buffered preservative group and the control group was not statistically significant (p = 0.24).

    Second study

    In a second study, the investigators also compared the formulations of travoprost and latanoprost, using preservative-free artificial tears in the control group. They followed the same protocol, treating 15 New Zealand white rabbits divided into three groups, with once-daily application of one of the three drops for 30 days.

    At the end of treatment, the central cornea of each rabbit was harvested, and transmission electron microscopy was performed on it. The number of desmosomal attachments per photomicrograph (3,400) was quantified and analyzed using Student's t-test to compare means between groups.


    Nancy Groves
    Nancy Groves is a freelance medical writer.

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