The Effect of Travoprost Z, Latanoprost and Their Individual Components on the Ocular Surface (Corneal and Conjunctival Epithelium).

Abstract

Purpose:: Prostaglandin analogues (PGAs) are the most common treatment for glaucoma. Most PGA formulations, like travoprost and latanoprost, contain the preservative benzalkonium chloride (BAK). Travoprost Z is preserved with a new ionic buffered preservative system, sofZia. To evaluate the potential toxicity of travoprost Z, travoprost, latanoprost and their components to the ocular surface, a tissue culture model utilizing immortalized corneal and conjunctival epithelial cells was utilized.

Methods:: Human conjunctival (CCC: P61 HCK) and corneal epithelial cells (HCE: CEPI 17) were used. At confluency, media was replaced with 100 µls of the commercial PGA formulations or their major components: travoprost Z 0.004%; travoprost 0.004% with benzalkonium chloride (BAK) 0.015%; latanoprost 0.005% with 0.02% BAK; as well as viable (cell media) and dead (formalin) controls. After 1 hour, the solution was removed and 150 µls of MTT were added to each well and incubated for 4 hours at 37^oC. After decanting, 100 µls of acid isopropanol was added. The absorbance was then determined at 572 nm and normalized, relative to the controls.

Results:: Travoprost Z exhibited 37.3% (CCC: 37.5%±2.5, HCE: 37.1%±6.6) < travatan 74.0% (CCC: 74.3%±1.7, HCE: 73.6%±1.5) < latanoprost 80.4% (CCC: 80.2%±1.5, HCE: 80.6%±1.8) toxicity. The active agents of the formulations were more toxic than controls [travoprost: 36.6% (CCC: 37.0%±4.2, HCE: 36.2%±1.5); latanoprost: 43.9% (CCC: 47.5%±3.4, HCE: 40.2%±1.4)]. BAK demonstrated the majority of the toxicity exhibited by the PGA formulations exhibiting an average toxicity of 77.1% at a concentration of 0.015% [that in travoprost: (CCC: 74.2%±2.1, HCE: 80.0%±1.0)], and 78.9% at 0.02% [that in latanoprost: (CCC: 76.1%±2.2, HCE: 81.7%±0.9)]. Increasing concentrations of BAK caused increased toxicity and BAK proved more toxic than the active agent.

Conclusions:: Preservatives exhibited the majority of the toxicity, travoprost Z exhibited the lowest: Travoprost Z < travoprost < latanoprost. BAK exhibited dose dependent toxicity and was more toxic than the active agents. Use of the non-BAK-preserved PGA, travoprost Z, seems to lead to less surface toxicity as evaluated in this model.

Keywords: drug toxicity/drug effects • cornea: epithelium • conjunctiva