Effects of common ophthalmic preservatives on ocular health

Noecker, Robert J.

doi:10.1007/bf02853166

Cited by 255 publications

(187 citation statements)

References 22 publications

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“…1 Preservatives can be classifi ed into four main categories: detergents, oxidants, chelating agents, and metabolic inhibitors (pentavalent antimonials [Sb V ], quaternary ammoniums, and organomercurials). 2,3 Examples of such preservatives include: benzalkonium chloride (BAK; detergent), chlorobutanol (Cbl; detergent), methyl paraben (MP; chelating agent), sodium perborate (SP; oxidative agent), and stabilized thimerosal (Thi; organomercurial); although by far, the most common of the topical ophthalmic medication preservatives is BAK, typically used in concentrations varying from 0.015% to 0.05%.…”

Section: Introductionmentioning

confidence: 99%

Comparative Toxicity of Preservatives on Immortalized Corneal and Conjunctival Epithelial Cells

Epstein

Ahdoot

Marcus

et al. 2009

Journal of Ocular Pharmacology and Therapeutics

167

105

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Purpose: Nearly all eye drops contain preservatives to decrease contamination. Nonpreservatives such as disodium-ethylene diamine tetra-acetate (EDTA) and phosphate-buffered saline are also regularly added as buffering agents. These components can add to the toxicity of eye drops and cause ocular surface disease. To evaluate the potential toxicity of these common components and their comparative effects on the ocular surface, a tissue culture model utilizing immortalized corneal and conjunctival epithelial cells was utilized. Methods: Immortalized human conjunctival and corneal epithelial cells were grown. At confl uency, medium was replaced with 100 μL of varying concentrations of preservatives: benzalkonium chloride (BAK), methyl paraben (MP), sodium perborate (SP), chlorobutanol (Cbl), and stabilized thimerosal (Thi); varying concentrations of buffer: EDTA; media (viable control); and formalin (dead control). After 1 h, solutions were replaced with 150 μL of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazonium bromide). After 4 h, solutions decanted, 100 μL of acid isopropanol added, and the optical density determined at 572 nm to evaluate cell viability. Results: Conjunctival and corneal cell toxicity was seen with all preservatives. Depending upon concentration, BAK exhibited from 56% to 89% toxicity. In comparison, Cbl exhibited from 50% to 86%, MP from 30% to 76%, SP from 23% to 59%, and Thi from 70% to 95%. EDTA with minimal toxicity (from 6% to 59%) was indistinguishable from SP. Conclusions: Generally, the order of decreasing toxicity at the most commonly used concentrations: Thi (0.0025%) > BAK (0.025%) > Cbl (0.25%) > MP (0.01%) > SP (0.0025%) ≈ EDTA (0.01%). Even at low concentration, these agents will cause some degree of ocular tissue damage.

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Section: Introductionmentioning

confidence: 99%

Comparative Toxicity of Preservatives on Immortalized Corneal and Conjunctival Epithelial Cells

Epstein

Ahdoot

Marcus

et al. 2009

Journal of Ocular Pharmacology and Therapeutics

167

105

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“…[5][6][7] One of the more common preservatives used today is benzalkonium chloride (BAK). 8 BAK is a quaternary ammonium compound whose antimicrobial activity arises from its ability to disrupt cell membranes and potentiate cell death. Along with its antimicrobial activity, BAK is toxic to the corneal epithelium as well as conjunctival epithelium and stroma.…”

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confidence: 99%

Effects of prostaglandin analog therapy on the ocular surface of glaucoma patients

Horsley

Kahook²

2009

OPTH

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Purpose: To quantify changes in tear break-up time (TBUT), corneal staining and ocular surface disease index (OSDI) in glaucoma patients after switching therapy from latanoprost with 0.02% benzalkonium chloride (BAK) to travoprost with sofZia ™ . Methods: Prospective consecutive case series evaluating patients before and 8 weeks after switching from latanoprost with BAK to travoprost with sofZia ™ in patients with baseline TBUT less than 6 seconds.Results: Forty eyes of 20 consecutive patients using latanoprost with BAK were switched to travoprost with sofZia ™ . Mean TBUT prior to starting travoprost was 2.02 ± 0.71 seconds and increased to 6.34 ± 1.31 seconds 8 weeks after the switch (p Ͻ 0.001). Mean inferior corneal staining scores decreased from 2.40 ± 0.87 to 1.38 ± 0.59 (p Ͻ 0.001). Mean OSDI scores decreased from 26.31 ± 8.25 to 16.56 ± 6.19 (p Ͻ 0.001). Discussion: This report focuses on the status of the ocular surface, as documented by TBUT, corneal staining and OSDI, in patients switched from latanoprost with BAK to travoprost without BAK. The switch resulted in a statistically signifi cant increase in TBUT and decreases in corneal staining and OSDI in patients with low baseline TBUT values. Conclusion: BAK, a common preservative for glaucoma drops, may increase OSD by disrupting the tear fi lm and increasing conjunctival infl ammation. In this study, a change from a BAK-preserved prostaglandin analog (PGA) to a non-BAK-preserved PGA resulted in a measurable improvement of TBUT, corneal staining and OSDI. Further studies are needed to better understand the impact of BAK-preserved medications on the ocular surface.

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“…However, the use of either of these to enhance EGF receptor activation clinically seems dubious. Benzalkonium chloride has severe adverse effects when applied to eyes (Noecker, 2001), and H 2 0 2 is also toxic and is rapidly deactivated by catalase in the tear film (Riley and Wilson, 1993).…”

Section: Discussionmentioning

confidence: 99%

Activation of the epidermal growth factor receptor by hydrogels in artificial tears

Lozano¹,

Chay²,

Healey³

et al. 2008

Experimental Eye Research

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Most formulations of artificial tears include high-molecular weight hydrophilic polymers (hydrogels) that are usually thought to serve to enhance viscosity and to act as demulcents. A few reports have indicated that application of some of the polymers accelerates healing of wounds in epithelia. Since activation of the epidermal growth factor (EGF) receptor is critical for spontaneous corneal epithelial wound healing, we tested commonly used hydrogels for their ability to activate the EGF receptor and enhance closure of wounds. Five structurally unrelated hydrogels used in artificial tears were found to activate the EGF receptor. Importantly, two of the hydrogels enhanced wound healing in an organ culture model. We propose that the efficacy of hydrogels in treating dry eye may be related to their ability to activate the EGF receptor, and that hydrogels are inexpensive, safe agents to promote healing of wounds in the cornea and possibly in other tissues.

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Effects of common ophthalmic preservatives on ocular health

Cited by 255 publications

References 22 publications

Comparative Toxicity of Preservatives on Immortalized Corneal and Conjunctival Epithelial Cells

Comparative Toxicity of Preservatives on Immortalized Corneal and Conjunctival Epithelial Cells

Effects of prostaglandin analog therapy on the ocular surface of glaucoma patients

Activation of the epidermal growth factor receptor by hydrogels in artificial tears

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