Effect of topical 0.02% tacrolimus aqueous suspension on tear production in dogs with keratoconjunctivitis sicca

Objective To investigate the effect of 0.02% tacrolimus in aqueous suspension on tear production in dogs with keratoconjunctivitis sicca (KCS). Animals studied One hundred five dogs diagnosed with KCS [Schirmer tear test (STT) <= 10 mm/min and clinical signs of dry eye]. Eyes with marginally decreased STT (11 <= 15 mm/min) and clinical signs of dry eye were also evaluated. Procedure The investigation was conducted in two Parts: an initial efficacy study and a subsequent double blinded controlled study. In the efficacy study, the effect of topical tacrolimus (formerly FK-506) on tear production in dogs with primary KCS was evaluated. Dogs were divided into four categories: 1) 59 eyes (38 dogs) naive to tear stimulation therapy with initial STT: 10 mm/min; 2) 28 eyes (21 dogs) naive to tear stimulation therapy with initial STT 11 <= 15 min/min; 3) 30 eyes (15 dogs) maintained successfully on CsA therapy; 4) 47 eyes (24 dogs) unresponsive to CsA therapy. STT and clinical signs were evaluated prior to and after 6 to 8 weeks of twice daily tacrolimus administration. Tacrolimus was substituted for CsA therapy in categories 3 and 4. The controlled study compared the effect of topical tacrolimus in aqueous suspension to administration of the aqueous carrier alone on tear production in 20 dogs with primary KCS. Results In the efficacy study, STT increased by >= 5 mm/min in 84.7%, 25.0%, 26.7% and 51.1% of eyes in categories 1, 2, 3 and 4 respectively after tacrolimus administration. Eighty-three percent of eyes with extremely low initial STT (<= 2 mm/min), increased >= 5 mm/min after tacrolimus. In the controlled study, STT increased by >= 5 mm/min in 7/10 dogs (14/2 0 eyes) that received tacrolimus and in none of the 10 dogs that received aqueous carrier alone. Dogs receiving just the aqueous carrier were subsequently treated with tacrolimus, and STT increased : 5 mm/min in 9 dogs (18/20 eyes) after administration. Conclusions Twice daily administration of 0.02% tacrolimus in aqueous suspension effectively increased tear production in dogs with KCS. Topical tacrolimus is a promising alternative to topical CsA for treatment of KCS and may be beneficial in patients with less than optimal response to topical CsA.