Tear Stimulants and Immunosuppressants in Animals

Immune-mediated keratoconjunctivitis sicca is not uncommon in dogs and is treated predominantly with topical cyclosporin A and tacrolimus. These are both calcineurin inhibitors and act as partial immunomodulators. The exact mechanism is not known; however, they block T-cell infiltration and activation and decrease T-cell inflammatory mediators that cause damage to lacrimal acini. They also increase natural tear production from viable glandular tissue in the absence of inflammation, possibly by effects on prolactin. Cyclosporine A is available as a 0.2% ointment; however, a compounded higher concentration (1% or 2%) is required in some cases. Topical 0.02%–0.03% tacrolimus is also used and is regarded as being 100 times more potent than cyclosporine. Both drugs are usually compounded in an oil formulation but can be formulated in an aqueous solution. There may be transient pain on instillation with corn or olive oil carriers, although some animals have longer periods of discomfort. Coconut oil is less irritating. Both drugs can be combined (1%–2% cyclosporine A/0.02–0.03% tacrolimus) for use in refractory cases or the tacrolimus dose can be increased to 0.1%–0.3%. It is very rare to see systemic toxicity (nephrotoxicity) and the drugs are essentially nontoxic to the cornea but can slow down healing.

Topical 0.02% sirolimus (rapamycin) aqueous solution has also been shown to increase tear production in dogs, though not by the inhibition of calcineurin but by decreased T- and B-cell function and down regulation of factors for immune cell activation and proliferation. Episcleral cyclosporine implants have shown to increase tear production and improve clinical signs in dogs for up to 18 months. Dilute pilocarpine (0.1%–0.2%) every 8 hours can be used in the treatment of neurogenic keratoconjunctivitis sicca.

Compounded oil or aqueous based cyclosporin A (1%–2%) is used on its own or in combination with 0.1% dexamethasone for the treatment of eosinophilic keratitis, immune-mediated keratitis, immune keratoconjunctivitis (pannus), plasmoma of the third eyelid, and episcleritis. Tacrolimus (0.02%–0.03%) can also be combined with 0.1% dexamethasone. Tacrolimus (0.02%–0.03%) on its own can also help thin dense corneal pigment to help improve vision.