The purpose of this paper was to determine the efficacy and safety of topical tacrolimus, compared to cyclosporine, for treating keratoconjunctivitis sicca (KCS) in dogs. This study was a two-phase, randomized, controlled, masked clinical trial. Phase 1 evaluated ophthalmic 0.03% tacrolimus in normal dogs. Ocular examinations were performed daily. Phase 2 evaluated the efficacy of tacrolimus in treating KCS. Half the dogs received 2% cyclosporine A; the others received 0.03% tacrolimus, both diluted in olive oil. Four ophthalmic examinations were done over 12 weeks. There was no significant difference between groups in phase I. In phase 2, there was no significant difference in Schirmer tear test I (STT) results between the two groups, and both groups had a significant increase in STT over time. Both drugs were effective in increasing the STT in dogs na？ve to lacrimostimulants. Tacrolimus was effective in increasing the STT in 4 dogs currently nonresponsive to cyclosporine. 1. Introduction Keratoconjunctivitis sicca (KCS) is a deficiency of the aqueous layer of the precorneal tear film. Clinical signs in dogs with KCS include mucopurulent ocular discharge, conjunctivitis, keratitis, and blepharospasm. Dogs with KCS have a Schirmer tear test I (STT) result of <10？mm/minute, and severely affected dogs often have an STT result of 0？mm/min. While many causes of KCS in dogs have been described [1–10], KCS in dogs is most often considered to be immune-mediated based on studies that showed increased numbers of lymphocytes and plasma cells with acinar atrophy in the lacrimal glands [11, 12]. Immune-mediated KCS is typically bilateral and affects many breeds. Treatment of immune-mediated KCS is aimed at decreasing the immune response in the lacrimal gland and restoring aqueous tear production. Cyclosporine A (CsA) is a commonly used and effective treatment for canine KCS [13–16]. Formulations typically used are previously commercially available as 0.2% CsA ophthalmic ointment (Optimmune), and 1% and 2% CsA in olive or corn oil [13–19]. In addition to increasing tear production by inhibiting T-helper lymphocyte proliferation and infiltration of lacrimal gland acini, CsA restores conjunctival goblet cell mucin production [12, 13, 17, 18]. Previous studies have shown that dogs treated with ophthalmic CsA treatment have a decreased lymphocyte stimulation index compared to control dogs and that there are measurable levels of CsA in peripheral blood of treated dogs [20, 21]. However, a more recent study did not show a change in the lymphocyte stimulation index or
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