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R Anwaruddin, L Herrygers, RJ Noecker; Effect of Preservatives on the Ocular Surface in Chronic Glaucoma Therapy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4088.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To compare the relative amount of corneal epithelial damage and conjunctival inflammation caused by chronic dosing of commonly used glaucoma medications. Most glaucoma medications contain benzalkonium chloride (BAC) preservative except Alphagan®P, which contains stabilized oxychloro complex (SOC). Methods:Each eye of 16 New Zealand white age-matched rabbits was randomized to receive one of six eyedrops for duration of one month. Eyedrops and dosages used were Trusopt® BID, timolol maleate 0.5% BID, Xalatan® qday, LumiganTM qday, Alphagan®P BID, and Refresh Tears® BID. Corneal specimens were examined with Scanning electron microscopy (SEM) and graded for damage by a blinded observer. Conjunctival biopsy specimens were prepared for light microscopy, stained with toluidine blue and were also examined in blinded fashion. Lymphocyte cell counts were performed in the conjunctival epithelium, and superficial and deep substantia propria. ANOVA and two-tailed t-tests were performed to compare corneal epithelial damage scores and conjunctival cell counts among the treatment groups. Results:Corneal epithelial damage scores from most to least were Trusopt®, Xalatan®, timolol maleate, LumiganTM, Alphagan®P and Refresh Tears®. Trusopt®, Xalatan®, and timolol maleate had damage scores that were statistically significantly greater than Refresh Tears® (p =1x10-9, p = 9x10-8, p = 1x10-2). Lymphocyte cell counts in the epithelium of the Trusopt®, timolol maleate and Xalatan® treatment groups were statistically significantly higher than in the Refresh Tears® treatment group (p=0.043, p=0.018, and p=0.034, respectively) and in the Alphagan®P treatment group (p=0.003, p=0.045, and p=0.008, respectively). Lymphocyte cell counts in the superficial substantia propria of the Trusopt® treatment group were statistically significantly higher than in the Refresh Tears® treatment group (p=0.049). Lymphocyte cell counts in the deep substantia propria of the Trusopt® treatment group were statistically significantly higher than in the Refresh Tears® and Alphagan®P treatment groups (p=0.011 and p=0.0002, respectively). Conclusion:Corneal epithelial damage due to chronic glaucoma medication use appears to multifactorial, related to pH, drug mechanism of action and amount of BAC. One-month usage of BAC-containing glaucoma medications resulted in significant inflammatory cell infiltration in the conjunctiva. Alphagan®P caused no significant increase in inflammatory cell infiltration of the conjunctiva compared to Refresh Tears®. These findings may be factors in choosing a glaucoma agent for chronic use.
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