Exploratory Study Reveals Topical Pimecrolimus Is Active Against Keratoconjunctivitis Sicca And Chronic Superficial Keratitis In Dogs.

Abstract

Abstract: : Purpose: Pimecrolimus is an ascomycin derivative which interferes selectively with the activation of T and mast cells and inhibits the production of inflammatory cytokines. This study evaluated the efficacy and irritative potential of an experimental ophthalmic formulation of pimecrolimus in treating keratoconjunctivitis sicca (KCS) and chronic superficial keratitis (CSK) in dogs. Methods: Twelve dogs with KCS and 17 with CSK were included. The affected eyes were treated with one drop of 1% pimecrolimus 3 times daily. Increase in Schirmer Tear Test (STT) values, decreased discharge, conjunctival / corneal alterations and discomfort were evaluated in KCS, and regression of pannus and associated phenomena in CSK. Increasing discomfort and conjunctival hyperemia following treatment were considered as signs of incompatibility with the test formulation. Results: The effect of pimecrolimus 1% was pronounced (STT values >4 mm/min, no inflammatory signs) or moderate (STT values of 3 – 4 mm/min, mild corneal / conjunctival inflammation) in 9 of 12 animals with KCS. In 14 of 17 animals with CSK, the effect was either pronounced (total regression of pannus, no corneal changes) or moderate (distinct regression of pannus, mild corneal changes). These findings are highly promising because all dogs had suffered from long–lasting eye diseases and most of them had been treated unsuccessfully prior to this study. In 2 cases with verified corticosteroid–resistance, pimecrolimus was therapeutically active. The response to treatment was unsatisfactory in 6 of the 29 animals, probably due to lack of activity at 1% and/or the irritating potential of the exploratory formulation which has not yet been galenically optimized. Conclusions: This first exploratory study revealed topical pimecrolimus is an interesting potential treatment of inflammatory eye conditions in dogs, such as KCS and CSK. Because KCS shares pathogenetic similarities with Sjögren’s syndrome, pimecrolimus may also be beneficial for the treatment of dry eye disease of humans.

Keywords: cornea: tears/tear film/dry eye • keratitis • immunomodulation/immunoregulation