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Editors Selection IGR 16-4

Medical Therapy: Effect BAK /PQ in PA+β-blocker on cultured TM cells

Comment by Tin Aung on:

46863 Effects of benzalkonium chloride- or polyquad-preserved fixed combination glaucoma medications on human trabecular meshwork cells, Ammar DA; Kahook MY, Molecular Vision, 2011; 17: 1806-1813

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Preservatives such as benzalkonium chloride (BAK) used in topical glaucoma medications are associated with ocular surface problems including changes in the tear film, damage of the corneal epithelium and chronic inflammatory changes in the conjunctiva. Such problems affect patients' comfort and tolerance, and contribute to reduced adherence to glaucoma therapy. Of note, BAK has been found to increase corneal permeability to hydrophilic agents, which can potentially lead to increased delivery of medications to the aqueous humour, with BAK itself also found to be absorbed into the aqueous.

In this interesting paper, Ammar and Kahook (1556) investigated the effect of various topical formulations of prostaglandin analogues plus beta-blocker fixed combination therapies containing varying concentrations of either BAK or polymer polyquad (PQ) preservatives on cultured human trabecular meshwork (TM) cells over 24 hours.These formulations were:

1. 0.004% travoprost with 0.5% timolol preserved with 0.015% BAK
2. 0.004% travoprost with 0.5% timolol preserved with 0.001% polyquad
3. 0.005% latanoprost with 0.5% timolol preserved with 0.02% BAK
4. BAK by itself with a range of concentrations (0.001% to 0.02%)

The study found that exposure to concentrations of BAK resulted in toxicity to TM cells in a direct dose-response relationship when assayed immediately after exposure. Exposure to 0.02% BAK over 24 hours also caused elevated levels of MMP-9, a matrix metalloproteinase implicated in the pathogenesis of glaucoma. In fixed-combination therapies preserved with BAK, exposure to travoprost/timolol resulted in greater percentage of live cells than latanoprost/timolol. The travoprost/timolol combination with PQ had better TM cell viability than that preserved with BAK. The clinical implications of this study's findings are that long term use of fixed combinations containing BAK could damage the TM by reducing the viability of TM cells. Such effects may also be possible with the use of other topical glaucoma medications containing BAK. This possibility is worrying as damage to the TM could theoretically negate intraocular pressure lowering benefits of such medications. This was a laboratory study of TM cell lines and there are likely to be differences in TM responses to BAK in vivo, compared to the in-vitro models used in this study. As noted by the authors, additional in vitro and in-vivo animal studies need to be performed to ascertain the true clinical implications of the study's findings for patients chronically treated with topical glaucoma medications.

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