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In Vitro Studies of Antiglaucomatous Prostaglandin Analogues: Travoprost with and without Benzalkonium Chloride and Preserved Latanoprost

¹From the Department of Ophthalmology 3, Quinze-Vingts National Ophthalmology Hospital, Paris, France; ²INSERM U872, Paris, F-75006 France; the ³Department of Ophthalmology, Ambroise Paré Hospital, APHP, University of Versailles, Versailles, France; and the ⁴Department of Toxicology, Faculty of Biological and Pharmacological Sciences, University of Paris Descartes, Paris, France.

PURPOSE. With use of the Wong-Kilbourne derivative Chang conjunctival cell line, this study compared in vitro the ocular toxicity of three topical intraocular pressure (IOP)–lowering agents: travoprost 0.004% containing 0.015% benzalkonium chloride (BAK), travoprost Z 0.004%, a new formulation without BAK, and latanoprost 0.005% containing 0.02% BAK.

METHODS. Neutral red, Alamar blue, YOPRO-1, and annexin V/7-AAD assays were used to evaluate the effects of the IOP-lowering agents and BAK on cellular viability, membrane integrity, and apoptosis in the conjunctival cell line using microtitration fluorometric analysis and flow cytometry. All assessments were performed in a masked manner.

RESULTS. Assessment of cell viability and membrane integrity revealed a significant effect by latanoprost with BAK or BAK alone but no effect by travoprost Z without BAK or buffer alone (P < 0.0001). Latanoprost with BAK, travoprost with BAK, and BAK alone were cytotoxic in Chang conjunctival cells, whereas no cytotoxicity was observed in cells exposed to travoprost Z without BAK or in cells treated with buffer (P < 0.0001). No increase in apoptosis or necrosis was observed in cells treated with control or travoprost Z without BAK compared with BAK, travoprost with BAK, and latanoprost with BAK (P < 0.0001).

CONCLUSIONS. Latanoprost with BAK, travoprost with BAK, and BAK alone have significant cytotoxic effects on human conjunctiva-derived cells and are associated with apoptosis. These effects likely result from BAK used as a preservative. IOP-lowering agents with alternative preservatives instead of BAK will most likely have fewer ocular surface adverse effects than agents containing BAK.

This article has been cited by other articles:

				H Liang, C Baudouin, A Pauly, and F Brignole-Baudouin Conjunctival and corneal reactions in rabbits following short- and repeated exposure to preservative-free tafluprost, commercially available latanoprost and 0.02% benzalkonium chloride Br. J. Ophthalmol., September 1, 2008; 92(9): 1275 - 1282. [Abstract] [Full Text] [PDF]