In Vitro Evaluation of the Ophthalmic Toxicity Profile of Chlorhexidine and Propamidine Isethionate Eye Drops

J Ocul Pharmacol Ther. 2017 Apr;33(3):202-209. doi: 10.1089/jop.2016.0053.

Abstract

Purpose: Acanthamoeba keratitis causes frequent epithelial lesions that fully expose the corneal stroma. The aim of this study was to determine the toxic profile of chlorhexidine and propamidine eye drops.

Methods: We used primary human keratocytes in cell culture in combination with a novel technology that evaluates dynamic real-time cytotoxicity through impedance analysis. Additional studies such as a classic cell viability test (WST-1®), a bovine corneal opacity and permeability assay, and an irritation eye study (Hen's Egg Test [HET]) have been made.

Results: Both eye drop formulations showed a time- and concentration-dependent toxicity profile, in which long periods and high concentrations were more detrimental to cells. In prolonged times of exposure, propamidine is more harmful to cells than chlorhexidine. On the contrary, no irritation has been detected in using the HET-chorioallantoic membrane test and no alterations in the corneal transparency nor permeability was produced by the treatment with both eye drops.

Conclusions: In culture assay, chlorhexidine eye drops have proven to be less cytotoxic than Brolene® for a long contact period of time, but no signs of irritation or alterations in transparency or permeability have been observed in the cornea after both treatments.

Keywords: Acanthamoeba; chlorhexidine; cornea; eye drops; keratitis; propamidine; toxicology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Testing Alternatives
  • Animals
  • Benzamidines / administration & dosage
  • Benzamidines / toxicity*
  • Cattle
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemistry, Pharmaceutical
  • Chlorhexidine / administration & dosage
  • Chlorhexidine / toxicity*
  • Cornea / drug effects
  • Corneal Keratocytes / drug effects*
  • Dose-Response Relationship, Drug
  • Eye / drug effects
  • Humans
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / toxicity*
  • Time Factors

Substances

  • Benzamidines
  • Ophthalmic Solutions
  • propamidine isethionate
  • Chlorhexidine