In vitro effects of preserved or preservative-free antiglaucoma medications on human complement system

Abstract

Carteolol, timolol, betaxolol and latanoprost did not activate complement system. On the contrary, the beta-blockers timolol and betaxolol exerted an anti-inflammatory effect by preventing complement activation. The deleterious effect of benzalkonium seems to have been neutralized within the preserved eyedrops through a mechanism that remains to be elucidated. Our study suggests that inflammatory signs in glaucoma patients should not be attributed to complement activation by antiglaucoma drugs.

Comparison of Corneal and Conjunctival Changes After Dosing of Travoprost Preserved With sofZia, Latanoprost With 0.02% Benzalkonium Chloride, and Preservative-free Artificial Tears

“…Multiple studies have documented the deleterious effects of BAK on the ocular surface, ranging from corneal epithelial damage to chronic lymphocytic infiltration and fibroblast proliferation. [1][2][3][4][5][6][7][8]11,12 A recent study by Malvitte et al 3 examined the inflammatory response to chronic topical glaucoma therapy in humans through tear cytokine levels by using multiplex bead analysis. Cytokines studied included interleukin (IL) 1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-colony stimulating factor, granulocyte-macrophage stimulating factor, interferon g, monocyte chemotactic Blunting of tips with #50% loss of surface microvilli 4…”

“…[1][2][3][4][5] Benzalkonium chloride (BAK) is the most commonly used preservative in topical multidose glaucoma medications. 6 It is a quaternary ammonium compound that acts as a detergent and disrupts bacterial cell membranes, leading to cell death.…”

“…Several studies have shown the deleterious effects of BAK, both in vitro and in vivo, on corneal and conjunctival epithelium and stroma. [1][2][3][4][5][6][7][8] The side effects of BAK seem to be dose and time dependent, increasing with larger amounts used for longer periods. Many patients using topical glaucoma medications frequently require long-term treatment with .1 medication, thus increasing the chance of BAK-related side effects.…”

Quantitative analysis of conjunctival goblet cells after chronic application of topical drops

“…4 These interventions may alleviate some signs or symptoms of the ocular surface problem rather than addressing the underlying risk factor for OSD, which is the chronic use of eye drops that contain significant amounts of the preservative benzalkonium chloride (BAK), found in the majority of ophthalmic medications. [5][6][7][8][9][10][11] BAK is the most commonly used preservative in topical multidose glaucoma medications. 10 It is a quaternary ammonium compound that breaks down bacterial cell membranes, eventually leading to cell death.…”

Scanning Electron Microscopy Applied to Impression Cytology for Conjunctival Damage From Glaucoma Therapy

“…[2][3][4][5][6] The most widely used preservative in topical multidose glaucoma medications is benzalkonium chloride (BAK), 7 whose side effects seem to be dose-and time-dependent. The need for long-term treatment with medication in primary open-angle glaucoma increases the risk of BAK-related adverse effects.…”