Abstract
Introduction
Chronic topical glaucoma therapy has been reported to cause deleterious changes to the ocular surface epithelial layers. We compare changes in the number of goblet cells after chronic exposure to latanoprost preserved with 0.02% benzalkonium chloride (BAK) eye drops (Xalatan®; Pfizer, NY, USA), travoprost preserved with sofZia® eye drops (Travatan Z®; Alcon, Fort Worth, TX, USA), or preservative-free artificial tears (Refresh Plus®; Allergan, Irvine, CA, USA).
Methods
Fifteen New Zealand white rabbits were randomised into groups of five (one eye was randomised for treatment) and received once-daily topical application of one of the three treatments for 30 days. Enucleation was performed at the end of the study followed by histologic analysis using mucin stains to identify goblet cells. Goblet cells were quantified and analysed using Student t tests to compare means between groups.
Results
Goblet cells per high-power field were 2.21 (±0.40) in the latanoprost with BAK group, 6.02 (±1.20) in the travoprost with sofZia group, and 7.03 (±1.33) in the preservative-free artificial tear group. The number of goblet cells in the latanoprost with BAK group was significantly lower than the other two groups (P=0.0001). There was no statistically significant difference in goblet cell numbers between the travoprost with sofZia and preservative-free artificial tear group (P=0.24).
Conclusion
Our study illustrates that, in this animal model, once-daily dosing of latanoprost with 0.02% BAK resulted in goblet cell loss compared with dosing with either travoprost with sofZia or preservative-free artificial tears.
Similar content being viewed by others
References
Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–267.
McKinnon SJ, Goldberg LD, Peeples P, Walt JG, Bramley TJ. Current management of glaucoma and the need for complete therapy. Am J Manag Care. 2008;14(suppl 1):S20–S27.
Asbell PA, Potapova N. Effects of topical antiglaucoma medications on the ocular surface. Ocul Surf. 2005;3:27–40.
Foulks GN. Topical cyclosporine for treatment of ocular surface disease. Int Ophthalmol Clin. 2006;46:105–122.
Noecker RJ, Herrygers LA, Anwaruddin R. Corneal and conjunctival changes caused by commonly used glaucoma medications. Cornea. 2004;23:490–496.
Blondin C, Hamard P, Cholley B, Haeffner-Cavaillon N, Baudouin C. In vitro effects of preserved or preservative-free antiglaucoma medications on human complement system. Curr Eye Res. 2003;27:253–259.
Malvitte L, Montange T, Vejux A, et al. Measurement of inflammatory cytokines by multicytokine assay in tears of patients with glaucoma topically treated with chronic drugs. Br J Ophthalmol. 2007;91:29–32.
Pisella PJ, Debbasch C, Hamard P, et al. Conjunctival proinflammatory and proapoptotic effects of latanoprost and preserved and unpreserved timolol: an ex vivo and in vitro study. Invest Ophthalmol Vis Sci. 2004;45:1360–1368.
De Saint Jean M, Debbasch C, Brignole F, et al. Relationship between in vitro toxicity of benzalkonium chloride (BAC) and preservative-induced dry eye. Adv Exp Med Biol. 2002;506:697–702.
Noecker R. Effects of common ophthalmic preservatives on ocular health. Adv Ther. 2001;18:205–215.
Whitson JT, Cavanagh HD, Lakshman N, Petroll WM. Assessment of corneal epithelial integrity after acute exposure to ocular hypotensive agents preserved with and without benzalkonium chloride. Adv Ther. 2006;23:663–671.
Yee RW, Norcom EG, Zhao XC. Comparison of the relative toxicity of travoprost 0.004% without benzalkonium chloride and latanoprost 0.005% in an immortalized human cornea epithelial cell culture system. Adv Ther. 2006;23:511–519.
Mundorf T, Williams R, Whitcup S, Felix C, Batoosingh A. A 3-month comparison of efficacy and safety of brimonidine-purite 0.15% and brimonidine 0.2% in patients with glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2003;19:37–44.
Lewis RA, Katz GJ, Weiss MJ, et al. Travoprost 0.004% with and without benzalkonium chloride: a comparison of safety and efficacy. J Glaucoma. 2007;16:98–103.
Gipson IK. Distribution of mucins at the ocular surface. Exp Eye Res. 2004;78:379–388.
Pflugfelder SC, De Paiva CS, Villarreal AL, Stern ME. Effects of sequential artificial tear and cyclosporine emulsion therapy on conjunctival goblet cell density and transforming growth factor-beta2 production. Cornea. 2008;27:64–69.
De Saint Jean M, Debbasch C, Brignole F, Rat P, Warnet JM, Baudouin C. Toxicity of preserved and unpreserved antiglaucoma topical drugs in an in vitro model of conjunctival cells. Curr Eye Res. 2000;20:85–94.
Harrison JJ, Turner RJ, Joo DA, et al. Copper and quaternary ammonium cations exert synergistic bactericidal and anti-biofilm activity against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2008. [Epub ahead of print.]
Ingram PR, Pitt AR, Wilson CG, Olejnik O, Spickett CM. A comparison of the effects of ocular preservatives on mammalian and microbial ATP and glutathione levels. Free Radic Res. 2004;38:739–750.
Patarca R, Rosenzwei JA, Zuniga AA, Fletcher MA. Benzalkonium salts: effects on G protein-mediated processes and surface membranes. Crit Rev Oncog. 2000;11:255–305.
Baudouin C. Side effects of antiglaucomatous drugs on the ocular surface. Curr Opin Ophthalmol. 1996;7:80–86.
Kahook MY, Noecker RJ. Comparison of corneal and conjunctival changes after dosing of travoprost preserved with sofZia, latanoprost with 0.02% benzalkonium chloride, and preservative-free artificial tears. Cornea. 2008;27:339–343.
Perez-Vilar J, Mabolo R. Gel-forming mucins. Notions from in vitro studies. Histol Histopathol. 2007;22:455–464.
Baudouin C, Riancho L, Warnet JM, Brignole F. In vitro studies of antiglaucomatous prostaglandin analogues: travoprost with and without benzalkonium chloride and preserved latanoprost. Invest Ophthalmol Vis Sci. 2007;9:4123–4128.
Sherwood MB, Grierson I, Millar L, Hitchings RA. Long-term morphologic effects of antiglaucoma drugs on the conjunctiva and Tenon’s capsule in glaucomatous patients. Ophthalmology. 1989;96:327–335.
Broadway DC, Grierson I, O’Brien C, Hitchings RA. Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile. Arch Ophthalmol. 1994;112:1437–1445.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kahook, M.Y., Noecker, R. Quantitative analysis of conjunctival goblet cells after chronic application of topical drops. Adv Therapy 25, 743–751 (2008). https://doi.org/10.1007/s12325-008-0078-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12325-008-0078-y