TDK conference 2024

Keratoconjunctivitis sicca (KCS) is a major and common ophthalmological problem in both animal and human health. The most predisposed breeds of dogs are the West Highland white terrier, the Cavalier King Charles spaniel, the Cocker spaniel and bulldogs, in which KCS reaches an incidence of 10-20%. The animals are mostly treated with cyclosporine eye ointment, but in about 25% of cases the therapy is unsuccessful. Pimecrolimus may be effective in the therapy of KCS but is not available as an authorised veterinary ointment formulation. In general, the success of ophthalmic formulations is often negatively affected by their poor bioavailability, therefore the use of conventional formulations is increasingly being replaced by innovative formulations.

The focus of our research was to develop a new ophthalmic formulation containing pimecrolimus, and to establish an in vivo experimental KCS model in which the therapeutic effect of the drug candidates can be studied. In this model, we developed KCS in New Zealand white rabbits (7 rabbits/group) using Concanavalin-A injection. The preparations containing pimecrolimus (0.1%; 0.5% and 1% pimecrolimus) were produced at the University of Szeged. In our further treatment groups, we used both control (vehicle) and conventional (corn oil vehicle) 0,5% pimecrolimus containing treatment solution as reference. Tear production during the treatments was measured by Schirmer test at 1, 2 and 3 minutes. Measurements were taken for 3 days before and 7 days after the development of the KCS. Statistical analysis was performed on the differences in the values obtained.

Based on our results, no significant difference was found between the groups in the amount in tear production measured in the given minutes on each treatment day, with a p value above 0.05 in all cases. However, at a 10% significance level, we obtained differences in tear production between the group receiving the 0.5% pimecrolimus preparation and the control group receiving the reference treatment on day 7, at the 2-minute Schirmer test measurement, and on day 5, at the 3-minute Schirmer test measurement. These results provide a valuable starting point for the further development of the KCS model, the design of a simpler, more standardised experimental system, and the further testing and development of the new ophthalmic formulations.