Keratoconjunctivitis sicca (KCS), also known as dry eye disease, is one of the most common ophthalmic disorders encountered in both ophthalmology clinics and general veterinary practice. Proper diagnosis and management of KCS can significantly improve quality of life for both patients and their owners. Furthermore, early and appropriate treatment can help preserve ocular comfort and maintain long-term vision in canine patients. KCS can be devastating to ocular surface health, particularly affecting the cornea, conjunctiva, and the third eyelid. The conjunctiva is a connective tissue that covers the sclera. This tissue plays very important roles in maintaining the overall integrity of the eye, including ensuring globe and eyelid movements are smooth, producing part of the tear film, immune surveillance functions via its conjunctival associated lymphoid tissue (CALT), barrier protection to microbial organisms and particulate matter, and preventing ocular surface desiccation. The conjunctival tissue can perform all these functions due to its many important structures including blood vessels, lymphatic vessels, nerves, melanocytes and pigment, and a surface microbial flora. Conjunctival anatomical zones include the palpebral conjunctiva that lines the inside of the eyelids, the bulbar conjunctiva that lines the globe itself, and the conjunctival fornices where these two areas reflect onto one another located superiorly and inferiorly. The third eyelid (nictitating membrane) is also lined by conjunctiva, including palpebral conjunctiva on the anterior surface and bulbar conjunctiva on the bulbar surface. The third eyelid contains a T-shaped cartilage with a vertical shaft and horizontal portion. The gland of the third eye lid is located at the base of the third eyelid on the bulbar surface. The third eyelid helps spread tears as it moves diagonally from the medial can thus to the superiotemporal aspect of the globe. It also helps physically protect the globe. Finally, the third eyelid is another important contributor to the tear film: the gland of the third eyelid produces 30-50% of the aqueous component of the tear film. This is why we don't recommend removing cherry eyes anymore. The precorneal tear film (PTF) is an extremely important structure in the eye required for optimal ocular surface health and vision. The tear film is the most refractive structure in the eye. Therefore, a proper tear film is required for perfect vision. Tear production can be classified as basal tearing (the constant base secretion of tears), reflex tearing (secondary to noxious stimuli/irritation),and the lacrimal lake (the pool of tears that sits inferiorly along the eyelid margin). The PTF is made up of 3 layers: the lipid layer, aqueous layer, and mucin layer. The lipid layer is the outermost layer of the PTF. It is produced by the meibomian glands that exit along the eyelid margin at the "gray line". This layer helps decrease evaporation of the tear film and contributes to a smooth even spread of tears over the entire cornea. The aqueous layer is the middle layer. This is the thickest layer. It is produced by the lacrimal gland (about 50-80%), gland of the third eyelid (30-50%), and accessory glands in some species. This layer has many important functions including lubrication of the ocular surface, providing the cornea with nutrition and oxygen, removing metabolic waste products and debris, and antibacterial/immune functions. With KCS, this is the portion of the tear film that is deficient, which is why the disease can be so detrimental to overall ocular surface health. The mucin layer is the innermost layer. It is produced by the goblet cells located within the conjunctivalepithelium. This layer functions to adhere the PTF to the corneal surface, help with lubrication, and prevent bacterial adherence to the cornea. The nasolacrimal drainage system is how all the secreted tears exit the surface of the eye. Tears are pushed into the medial canthus every time a dog blinks, since the eyelids move in a zipper-like fashion from lateral to medial. The tears enter the superior and inferior punctum located at a few millimeters from the medial can thus just inside the eyelid margin. The inferior punctum is much more important for drainage of tears due to gravity. Following entrance into the puncta, the tears enter the superior and inferior canaliculi. These join at the lacrimal sac located within the lacrimal bone. The tears then enter the nasolacrimal duct which traverses to the nasal punctum. Tears exit at the nasalpunctum in each nostril (located a few millimeters from the nares). Tear production is constantly balanced with both tear evaporation and drainage of tears into the nasolacrimal duct system. A breakdown in any one of these components – the distribution of tears, the drainage of tears, or the production of tears like with KCS – can cause ocular surface disease and predispose the ocular surface to irritation, inflammation, ulceration, and more. Ruling out other ocular diseases is the first step, and arguably the most important step, when attempting to diagnose KCS. One of the most common ocular complaints from owners is regarding a"red eye". There are numerous causes of red eye, such as glaucoma, hyphema, uveitis, keratitis, orbital disease, episcleritis, and more. Some of these causes can be easily diagnosed on examination such as hyphema. However, other causes of a "red eye" can be more elusive, such as episcleritis, which could easily be mistaken for KCS on examination alone. This highlights the importance of a thorough ophthalmic examination including the ophthalmic minimum database (Schirmer tear tests, intraocular pressures, and fluorescein stain). These steps are vital in ensuring you don't misdiagnose a case of KCS as another ocular disorder such as inflammatory conjunctivitis. KCS can occur in any dog breed; however, some predisposed breeds include Bulldogs, Pugs,Cavalier King Charles Spaniels, Shih Tzus, West Highland White Terriers, Yorkshire Terriers, andBoston Terriers. KCS is characterized by a deficiency in the aqueous portion of the PTF. Clinical signsinclude thick mucoid discharge, a lackluster cornea, blepharospasm, conjunctival hyperemia and/orchemosis, corneal vascularization, corneal pigmentation, corneal fibrosis, and ulceration. Diagnosisrelies on performing a Schirmer tear test (STT). This test should be performed first, prior to anytopical anesthesia or other medications being placed in the eye, for accurate readings. This testmeasures the lacrimal lake, basal tear production, and reflex tearing. Normal STT values are greaterthan 15 mm of wetting in 1 minute. There are various causes of KCS that must be considered in a patient diagnosed with thedisease. The most common cause of KCS includes immune-mediated lymphoplasmacytic lacrimaladenitis causing destruction of the lacrimal glands and secondary decrease in aqueous tearproduction. KCS can also be due to drug reactions, developing secondary to medications such astrimethoprim-sulfonamide (TMS) or topical atropine. TMS can cause permanent and medicallynonresponsive KCS, therefore patients on this medication should have STTs monitored regularly. If adecrease in tear production is noted early on, then the medication should be discontinued wheneverpossible. If discontinued early on, the effects may be reversible. Topical atropine should be avoided inpatients with dry eye due to the negative effects on tear production. Iatrogenic KCS can be secondary to third eyelid gland removal, third eyelid removal (such as for an adenocarcinoma of the gland of the third eyelid), or ionizing radiation for a head or orbital tumor. Congenital KCS occurs secondary to lacrimal gland hypoplasia or aplasia. Inflammatory or traumatic orbital disease can cause direct damage to the lacrimal gland or its parasympathetic innervation. For example, proptosis commonly leads to KCS as a sequela in dogs. Metabolic diseases including diabetes mellitus or hypothyroidism can be associated with KCS. Finally, temporary decreases in tear production (but not necessarily true or persistent KCS) can be seen with general anesthesia, topical anesthesia (proparacaine or other),or systemic illnesses. Neurogenic dry eye is another important category of KCS. This form of KCS occurs when the parasympathetic innervation to the lacrimal gland is disrupted. These parasympathetic nerve fibers run with the facial nerve. The most common cause is idiopathic. However, other causes such as inflammation, compression from space-occupying lesions, or otitis could also cause this form of KCS. Examination alone can help you distinguish this form of dry eye from the other causes in a lot of cases. With neurogenic dry eye, disease is usually unilateral. Furthermore, because the parasympathetic fibers also innervate the nasal glands, this form of KCS is usually associated with an ipsilateral dry and crusted nostril. The treatment goals of any form of KCS are the same. Tears should be supplemented with lacrimomimetics (artificial tears). Tear production should be stimulated with a lacrimostimulant. Inflammation should be controlled. This is achieved by increasing tear production and by using topical steroids. Finally, the eye should be kept clean, and any secondary bacterial infections should be addressed. Artificial tears can be purchased over the counter from human pharmacies. These should be used as supplemental therapy only, as they are not enough to treat true dry eye alone. In humans, preservative-free artificial tears are often recommended, as preservatives can damage the corneal epithelium at high frequency administration and humans are administering artificial tears possibly more than once every hour for dry eye. However, dogs usually receive these medications three times daily, as that is what is feasible for owners. Therefore, it is generally regarded as safe to use artificial tears that contain preservatives. Tear production should be increased via use of calcineurin inhibitors – cyclosporine or tacrolimus. These medications have direct tear stimulating activity, yet they also block transcription of interleukin-2, thereby acting as T cell suppressors. Therefore, these medications help target the underlying cause of immune-mediated KCS. Both medications come in ointment or solution formulations. Typically, treatment is initiated at a frequency of one to three times daily depending on severity. These medications are almost always required lifelong. Topical steroids are also often used to treat ocular surface inflammation secondary to KCS. Patients should always receive a fluorescein stain first to ensure there is no active ulceration, as KCS predisposes to corneal ulcers. Finally, owners should be instructed on how to keep the eyes clean. The thick mucoid discharge acts as a barrier to penetration of topical medications. Owners can clean the eyes with ocular saline solution. Furthermore, secondary bacterial overgrowth may develop in the face of the mucoid discharge associated with KCS. Therefore, topical antibiotics may sometimes be used to decrease bacterial overgrowth. Neurogenic KCS is treated somewhat differently. The main treatment goals are still the same,however pilocarpine is the tear stimulant medication of choice. This medication is a direct acting parasympathomimetic that will increase lacrimation. Topical versus oral pilocarpine administration depends on the patient's tolerance. You may choose to institute topical pilocarpine therapy first, as this route usually comes with less risk of systemic side effects (vomiting or diarrhea). Topical 1%ophthalmic pilocarpine solution should be diluted at a 1:10 dilution with artificial tears to form a 0.1% solution (1% pilocarpine is too irritating for the ocular surface). This diluted solution is classically administered three times daily, as neurogenic KCS cases are typically severe. If patients do not tolerate this medication topically, then oral pilocarpine administration can be tried. Oral pilocarpine tablets should never be administered to dogs, as this carries a high risk of organophosphate toxicity. Instead, the 1% or 2% ophthalmic pilocarpine solution can be administered orally. A good starting dose is 1 drop per 10 kilograms of body weight every 12 hours. If no response is seen after a few weeks, then the dose can be adjusted by increasing by 1 drop at each dosing interval until a good response is seen or signs of systemic toxicity develop. If signs of systemic toxicity develop, the dose should be decreased back down to the previously tolerated dose. The parotid duct transposition (PDT) is a surgical salvage procedure used to treat medically refractory cases of KCS in dogs. This surgery involves transposing the parotid salivary duct from the mouth to the inferior conjunctival fornix, resulting in saliva draining onto the ocular surface as a "tear substitute". Because this is a salvage procedure, only dogs that are truly refractive to maximum medical therapy for at least 8 weeks or longer should be considered. Patient selection is key. Lifelong medications are still required after this procedure. The patients can develop numerous secondary complications such as corneal inflammation, tartar deposits, mineral deposits, irritation, and others. There is an approximate 50% complication rate with this procedure, again emphasizing its role as a salvage procedure.