Draft Statement by ANZGIG on Preservatives in Glaucoma Eye Drops               TOC

1. Benzalkonium chloride (BAK) can precipitate or aggravate underlying ocular surface disease (OSD). 1-11

2. OSD has an increasing frequency with increasing age, 12-14 and is thus relatively common in the older population, which includes most glaucoma patients. 15-16

3. There is potential toxicity to the surface of the eye by chronic use of potent preservatives, especially BAK, which is common to almost all anti-glaucoma medications. 17-19 About 50% of glaucoma patients require two or more medications, necessitating multiple exposures to BAK on a daily basis. 17-19

4. The concentration of BAK in commercially available eye drops ranges from 0.004% to 0.025%. 19 Research in animals suggests that adverse effects on tear film can occur from concentrations as low as 0.001%, and in cell studies in concentrations as low as 0.0001%. 19

5. As "gentler" preservatives or preservative-free anti-glaucoma preparations offer significant advantages symptomatically and objectively to glaucoma patients, 20-26 ANZGIG supports efforts by members of the pharmaceutical industry to provide these for our patients.

 
References

1 Kuppens EV, de Jong CA, Stolwijk TR, de Keizer RJ, van Best JA. Effect of timolol with and without preservative on the basal tear turnover in glaucoma. Br J Ophthalmol. 1995, 79:339-42

2 Mietz H, Niesen U, Krieglstein GK. The effect of preservatives and antiglaucomatous medication on the histopathology of the conjunctiva. Graefes Arch Clin Exp Ophthalmol. 1994, 232:561-5

3 Hughes EH, Pretorius M, Eleftheriadis H, Liu CS. Long-term recovery of the human corneal endothelium after toxic injury by benzalkonium chloride. Br J Ophthalmol. 2007, 91:1460-3

4 Cha SH, Lee JS, Oum BS, Kim CD. Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) in vitro. Clin Experiment Ophthalmol. 2004, 32:657

5 Kaercher T, Hönig D, Barth W. How the most common preservative affects the Meibomian lipid layer. Orbit. 1999, 18:89-97

6 Albietz JM, Bruce AS. The conjunctival epithelium in dry eye subtypes: effect of preserved and non-preserved topical treatments. Curr Eye Res. 2001, 22:8-18

7 Debbasch C, Brignole F, Pisella PJ, Warnet JM, Rat P, Baudouin C. Quaternary ammoniums and other preservatives' contribution in oxidative stress and apoptosis on Chang conjunctival cells. Invest Ophthalmol Vis Sci. 2001, 42:642-52

8 Adams J, Wilcox MJ, Trousdale MD, Chien DS, Shimizu RW. Morphologic and physiologic effects of artificial tear formulations on corneal epithelial derived cells. Cornea. 1992, 11:234-41

9 Tripathi BJ, Tripathi RC, Kolli SP. Cytotoxicity of ophthalmic preservatives on human corneal epithelium. Lens Eye Toxic Res. 1992, 9:361-75

10 Wilson WS, Duncan AJ, Jay JL. Effect of benzalkonium chloride on the stability of the precorneal tear film in rabbit and man. Br J Ophthalmol. 1975, 59:667-9

11 Tonjum AM. Effects of benzalkonium chloride upon the corneal epithelium studied with scanning electron microscopy. Acta Ophthalmol (Copenh). 1975, 53:358-66

12 Schaumberg DA, Dana R, Buring JE, Sullivan DA. Prevalence of dry eye disease among US men: estimates from the Physicians' Health Studies. Arch Ophthalmol. 2009 , 127:763-8

13 Moss SE, Klein R, Klein BE. Long-term incidence of dry eye in an older population. Optom Vis Sci. 2008, 85:668-74

14 The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007, 5:93-107

15 Coleman AL, Miglior S. Risk factors for glaucoma onset and progression. Surv Ophthalmol. 2008, 53:S3-10

16 Wong TY, Loon SC, Saw SM. The epidemiology of age related eye diseases in Asia. Br J Ophthalmol. 2006, 90:506-11

17 Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008, 17:350-5

18 Fechtner RD, Godfrey DG, Budenz D, Stewart JA, Stewart WC, Jasek MC. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea 2010 [Epub ahead of print]

19 Baudouin C. Detrimental effect of preservatives in eyedrops: implications for the treatment of glaucoma. Acta Ophthalmol. 2008, 86:716-26

20 Jaenen N, Baudouin C, Pouliquen P, Manni G, Figueiredo A, Zeyen T. Ocular symptoms and signs with preserved and preservative-free glaucoma medications. Eur J Ophthalmol. 2007, 17:341-9

21 Yee RW. The effect of drop vehicle on the efficacy and side effects of topical glaucoma therapy: a review. Curr Opin Ophthalmol. 2007, 18:134-9

22 Ishibashi T, Yokoi N, Kinoshita S. Comparison of the short-term effects on the human corneal surface of topical timolol maleate with and without benzalkonium chloride. J Glaucoma. 2003 Dec;12(6):486-90

23 Pisella PJ, Pouliquen P, Baudouin C. Prevalence of ocular symptoms and signs with preserved and preservative free glaucoma medication. Br J Ophthalmol. 2002 Apr;86(4):418-23

24 Kaur IP, Lal S, Rana C, Kakkar S, Singh H. Ocular preservatives: associated risks and newer options. Cutan Ocul Toxicol. 2009, 28:93-103

25 Noecker R. Effects of common ophthalmic preservatives on ocular health. Adv Ther. 2001, 18:205-15

26 Burstein NL. Corneal cytotoxicity of topically applied drugs, vehicles and preservatives. Surv Ophthalmol. 1980, 25:15-30

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