title: [In vivo assessment of corneal epithelial toxicity of timolol with benzalkonium chloride using very-high-frequency ultrasound imaging].
abstract: OBJECTIVE
  To assess in vivo the corneal epithelial damage caused by a topical toxic medication using a 60-MHz ultrasound device.
  
  
  METHODS
  and methods: A solution of timolol with 0.01% benzalkonium chloride (BAC) was applied twice a day in the test eyes of ten rabbits, and a BAC-free solution of timolol in the control eyes, for 56 days. We used a 60-MHz ultrasound device to evaluate the epithelial damage in BAC-exposed eyes, compared to control eyes. The clinical and ultrasound examinations were performed every week, and the histological analysis at the end of the experiment.
  
  
  RESULTS
  The clinical findings were conjunctival redness, corneal staining and instability of the tear film. In vivo VHF ultrasound revealed a thinning of the epithelium of test eyes (from 40.9+/-1,6 microm at D0 to 31.8+/-3.4 microm at D56; p=0.0006 for D0 vs D56), while the epithelium of control eyes remained unchanged. Ultrasound epithelial thickness was correlated with corneal staining (at D34 and D56; p=0.0025 and 0.0377, respectively) and histological epithelial pachymetry (p=0.0176 for control and 0.0505 for tested epithelium). Moreover, we report qualitative VHF ultrasound imaging of early epithelial damage.
  
  
  CONCLUSIONS
  This new device could be very useful in ocular toxicity evaluation as a reproducible and reliable tool for multicentric clinical research.
authors.affiliation: Service d'Ophtalmologie, Centre Hospitalo-Universitaire Bretonneau, Tours.
authors.forename: A
authors.initials: A
authors.lastname: Denoyer
authors.forename: F
authors.initials: F
authors.lastname: Ossant
authors.forename: B
authors.initials: B
authors.lastname: Arbeille
authors.forename: F
authors.initials: F
authors.lastname: Fetissof
authors.forename: F
authors.initials: F
authors.lastname: Patat
authors.forename: P-J
authors.initials: PJ
authors.lastname: Pisella
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds / Q000633:toxicity*; D004338:Drug Combinations; D019573:Epithelium, Corneal / Q000000981:diagnostic imaging* / Q000187:drug effects*; D008297:Male; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D011817:Rabbits; D013999:Timolol / Q000633:toxicity*; D014463:Ultrasonography
chemical_list: D001548:Benzalkonium Compounds; D004338:Drug Combinations; D011310:Preservatives, Pharmaceutical; D013999:Timolol