Lacrimostimulants are agents that increase or stimulate natural tear production. Cyclosporine and tacrolimus inhibit T-cell
activation and improve natural tear production by a minimizing the T-cell attack on the lacrimal gland and by directly lacrimal
stimulation. They are presently the most effective treatments for canine KCS. Cyclosporine is commercially available as a
0.2% ointment (Optimmune) but can be compounded in stronger concentrations as a 1% or 2% drop or ointment. Caution should
be taken with the use of 2% cyclosporine as one study showed systemic immunosuppression when used in "small dogs". Tacrolimus
is usually compounded as a 0.02% or 0.03% drop or ointment. Either drug can be formulated in an oil or aqueous base. Aqueous-based
formulations are easier for owners to apply and may be less irritating than oil-based preparations. Which drug to use depends
on personal preference, prior treatment, and severity of the KCS. A stronger formulation is indicated in patients unresponsive
to the 0.2% ointment. There is more data on cyclosporine than tacrolimus, but in one study, almost 50% of dogs that were some
non-responsive to cyclosporine improved after treatment with tacrolimus. The frequency of application for either drug is typically
twice daily, but treatments can be increased to three times daily if response is inadequate. Up to three months of treatment
can be required to see the full extent of the response to topical immunomodulators. Normally an improvement in clinical signs
is rapid, but three months of treatment is recommended prior to declaring medical failure. Both drugs appear to improve patient
comfort and reduce corneal inflammation, scarring, and pigment. In pets that do not respond with improved tear production,
continued treatment is still advised to prolong vision and comfort. Some ophthalmologists advocate combination treatment
with cyclosporine and tacrolimus in patients that respond inadequately to either drug alone, but such treatment is controversial.
Pilocarpine has historically been used for lacrimostimuation. Two percent pilocarpine at a dosage of 1-2 drops/25 pounds body
weight BID in the food is a good starting dose. The dosage is gradually increased until a response is observed or signs of
toxicity develop. Toxic signs include salivation, bradycardia, vomiting, or diarrhea. Pilocarpine is mentioned here for completeness,
but since cyclosporine was introduced, it has declined in popularity.
Judiciously applied topical corticosteroids are beneficial for many dry eye patients to reduce conjunctival and corneal inflammation
and corneal vascular infiltrates. However, pets with KCS are at greater risk for corneal ulceration, and caution is advised,
especially in pets with negligible tear production. Neo-poly-bac with hydrocortisone ointment is a good first choice because
the steroid is relatively mild but sufficiently strong to be of benefit.
Natural tears have antibacterial properties, so it is not surprising that bacterial infections are common with dry eye. Cyclosporine
treatments have been shown to decrease ocular bacterial infection because of improved tear production. Topical and or systemic
antibiotic treatment is indicated in many KCS patients.
Tear production should be checked two weeks after initiating treatment and periodically thereafter. Cyclosporine or tacrolimus
treatments are modified depending on patient response. In dogs with restoration of normal tear production (>15 mm/minute),
it may eventually be possible to reduce cyclosporine or tacrolimus to once daily and discontinue other topical treatments.
Parotid duct transposition surgery should be considered for dogs that have not responded months of appropriate treatment.
Parotid Duct Transposition
Parotid duct transposition (PDT) surgery should be considered in dry eye patients that are unresponsive to treatments, which
remain uncomfortable, or experience recurrent corneal ulcers. Saliva is similar enough in composition to tears to be an acceptable
substitute. Possible complications of PDT surgery include mineral precipitates on the cornea and eyelids, chronic epiphora,
facial dermatitis, and post-operative stenosis of the parotid duct. Mineral precipitates are the most common complication
but can usually be managed with daily cleaning of the eyelids and periodic removal from the corneal surface with a cellulose
surgical spear (e.g., 2-3 times annually). Topical 1.38% EDTA solution several times daily may be helpful in reducing deposits.
Dietary management can also be helpful, and diet low in mineral content is advised for problem cases.