[In vivo assessment of corneal epithelial toxicity of timolol with benzalkonium chloride using very-high-frequency ultrasound imaging].

Purpose: To assess in vivo the corneal epithelial damage caused by a topical toxic medication using a 60-MHz ultrasound device.

Material: 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.

Conclusion: This new device could be very useful in ocular toxicity evaluation as a reproducible and reliable tool for multicentric clinical research.