April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
In vivo Studies of Toxic Profiles of Antiglaucomatous Prostaglandin Analogues in Cationic Emulsion Formulation
Author Affiliations & Notes
  • H. Liang
    Umrs968, inserm upmc, Institute of Vision, University of Paris 6, Paris, France
    Department of Toxicology, Faculty of Biological and Pharmacological Sciences, Paris, France
  • F. Brignole-Baudouin
    Umrs968, inserm upmc, Institute of Vision, University of Paris 6, Paris, France
    Department of Toxicology, Faculty of Biological and Pharmacological Sciences, Paris, France
  • M. Faure
    Novagali Pharma SA, 91058 Evry, France
  • G. Lambert
    Novagali Pharma SA, 91058 Evry, France
  • C. Baudouin
    Umrs968, inserm upmc, Institute of Vision, University of Paris 6, Paris, France
    Department of Ophthalmology III, Quinze-Vingts National Ophthalmology Hospital, Paris, France
  • Footnotes
    Commercial Relationships  H. Liang, Dr. Liang H was supported by a grant of the « Conventions industrielles de formation par la recherche (CIFRE) » from the « Association nationale de la recherche technique (ANRT) » by Novagali Pharma S, F; F. Brignole-Baudouin, None; M. Faure, None; G. Lambert, None; C. Baudouin, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4781. doi:
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      H. Liang, F. Brignole-Baudouin, M. Faure, G. Lambert, C. Baudouin; In vivo Studies of Toxic Profiles of Antiglaucomatous Prostaglandin Analogues in Cationic Emulsion Formulation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4781.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Using an established rabbit toxicological model, this study compared in vivo the ocular toxicity of five topical intraocular pressure (IOP)-lowering agents: the commercial benzalkonium chloride (BAC)-containing solutions of 0.005% latanoprost, 0.004% travoprost, 0.03% bimatoprost (containing respectively 0.02%, 0.015%, 0.005% BAC), BAC-free 0.004% travoprost Z, and 0.005% latanoprost in a new cationic emulsion (LCEm) formulation.

Methods: : Thirty adult male New Zealand albino rabbits were used in this study. They were randomly divided into five groups: 50 µl of each formulation were applied onto rabbit eyes 15 times at 5-min intervals. The ocular surface changes were investigated using slit-lamp examination, corneal in vivo confocal microscopy (IVCM), flow cytometry (FCM), and conjunctival impression cytology (IC).

Results: : Antiglaucoma eye drops induced an ocular surface toxicity primarily related to the concentration of their common preservative BAC (latanoprost>travoprost>bimatoprost). LCEm did not induce obvious toxicity to rabbit ocular surface, just as BAC-free travoprost, by showing almost normal aspect of conjunctiva/cornea by clinical observation, CALT-IVCM analysis and IC evaluation.

Conclusions: : These in vivo and ex vivo experimental toxicological studies confirmed the ocular surface toxicity of antiglaucomatous BAC-containing eye drop solutions. BAC-free cationic emulsion of latanoprost (LCEm) and travoprost Z were well tolerated and did not induce ocular surface damages. The IOP-lowering eye drop LCEmwill most likely have fewer ocular surface adverse effects than formulations containing preservative BAC.

Keywords: ocular irritancy/toxicity testing • inflammation • microscopy: confocal/tunneling 
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