Keratoconjunctivitis Sicca--Introduction and Case Reports
World Small Animal Veterinary Association World Congress Proceedings, 2006
Jiri Beranek, DVM
Veterinary Clinic
Pardubice, Czech Republic

Keratoconjunctivitis sicca (KCS) is a chronic progressive inflammatory and degenerative disease associated with deficient or absent production of preocular tear film. In the most cases it requires a lifelong therapy. It is a serious disease, particularly when its chronic course induces conjunctivitis and keratitis.

Exact etiology of this disease remains unknown. Congenital anomalies, traumatic events, systemic or local infectious diseases, chronic lacrimal adenitis, toxic effects of drugs, neurogenic and idiopathic causes or autoimmune processes with a breed predilection are considered to be causes of KCS. The etiology has been categorized by Slatter as follows:

1.  Drug-induced KCS: phenazopyridine, sulfadiazine and sulfasalazine derivatives cause KCS mainly in elderly dogs. Appearance of KCS cannot be excluded even after repeated topical application of atropine.

2.  Surgically induced KCS: can happen as a result of surgical removal of prolapsed lacrimal gland of the nictitating membrane.

3.  Idiopathic causes of KCS: majority of KCS cases associated with reduction of cytoplasmic secretory granules in the glandular cells of both lacrimal glands (including senile atrophy of granules) are included in this group.

4.  Autoimmune KCS: more than 30% of cases of destruction of the lacrimal gland and gland of the nictitating membrane are associated with the immune system. Dogs with diagnosed KCS reveal higher affinity to endocrinopathies, such as hypothyroidism, diabetes mellitus, hyper- or hypoadrenocorticism, rheumatoid arthritis, lupus erythematosus, complex pemphigus, and Cushing syndrome or to conditions, such as polymyositis, polyarthritis, atopy, pyoderma, seborrhoea, glomerulonephritis, and ulcerous colitis.

5.  Orbital and supraorbital injuries: may influence function of lacrimal glands either directly or via damage of their nerves.

6.  Febris contagiosa canum: distemper virus affects both lacrimal gland and the gland of the nictitating membrane temporarily or even permanently.

7.  Other causes: all other cases, which do not fit into the previous categories, are counted into this group, e.g., KCS following radiotherapy or vitamin A deficiency.

KCS is a disease with a proven breed predisposition for breeds, such as shi-tzu, Lhasa-apso, Pekinese, English bulldog, West Highland white terrier, Cocker spaniel, mopse, Yorkshire terrier, Miniature Poodle, Schnauzer, Chinese crested dog. Congenital KCS occurs mostly unilaterally in small breeds. The highest occurrence of the disease was observed at the age between 4 and 7 years. The likelihood of disease occurrence increases with age.

A less frequent occurrence of KCS is reported in cats. One of the possible diagnostic factors may be lower STT values as compared with dogs.

Clinical signs of the KCS are various and depend on the severity of disease, acute or chronic stage, and unilateral or bilateral occurrence.

The typical signs are:

 Blepharospasms: Is frequently observed as a first sign of the disease. It is caused by corneal irritation as a result of changes in the tear fluid. It may be associated with photophobia.

 Mucoid or mucopurulent discharge: In the absence of the aqueous layer of the tear film, mucoid layer of the tear film is insufficiently eliminated from the eye and can be seen dry around the palpebral rim. This is together with conjunctivitis one of the early signs of KCS.

 Corneal ulceration: Is described mainly in chronic cases where loss of epithelium occurs in the central corneal area. This condition may lead to corneal perforation and endophthalmitis.

 Corneal vascularization and pigmentation: Deepness and extent of the corneal changes correlates with the disease chronicity.

 Corneal xerosis and conjunctival redness: Dry appearance of the cornea is typical.

 Dry ipsilateral nostril.

 Chronic staphylococcus infection with good responses to antibiotics.

Diagnose of KCS is based on clinical signs, staining with bengal red, which detects dead cells and epithelial lesions, as well as staining with fluorescein, which stains corneal ulcerations. Schirmer tear test (STT) is a standard approach to assessment of tear production. Recommended interpretation is as follows: normal tear production amounts to 15 mm/min. and more on the test strip; beginning or subclinical KCS shows 11-14 mm/min., slight to moderate KCS results in 6-10 mm/min., and severe cases of KCS are associated with values below 5 mm/min. In dogs with ulcerative keratitis and dogs treated with atropine repeated examinations are recommended. Diagnose of KCS can be postulated in the presence of a mucopurulent conjunctivitis, corneal ulceration, and pigment deposition in the cornea, associated with low STT values.

Due to similarity of clinical signs caused by bacterial infections or allergic conditions of the eye, KCS frequently remains undiagnosed. Results are corneal ulcerations, descemetocele with corneal perforations and following infections of deeper eye structures.

Therapy of KCS requires an individual approach to each patient and drugs used have to address specific severity grades of the disease. The most frequently used drugs are combinations of tear production stimulating drugs, artificial tears, mucinolytic preparations, and topical application of antibacterial and anti-inflammatory drugs.

Historically, pilocarpin was topically or orally used for stimulation of parasympathetic nerves of the lacrimal gland in order to increase tear production during KCS. Due to a number of adverse side-effects (local irritation, bradycardia, hypersalivation, vomiting, and diarrhea) and a failure to prove a significant improvement in tear production, the clinical usage of pilocarpin was abandoned.

A significant change in therapy of KCS was brought by introduction of immunosuppressive drugs, such as cyclosporin A (Sandimmun, Sandoz) in the year 1989. Although the mechanism of action of cyclosporin A in the KCS is not quite known, its immunomodulatory and secretion stimulating effects on lacrimal glands are successfully used. The therapeutic effect can already be seen during the first treatment days. Time for stabilization of the clinical condition and increase of the tear production is usually at least 8-9 weeks. Treatment failures with cyclosporin A are ascribed to atrophy or a total depletion of secretory tissue of the lacrimal gland. Cyclosporin also reduces vascularization and pigmentation of the cornea in chronic corneal processes. It is used dissolved in corn oil or olive oil at concentrations of 0.5-2%, applied twice daily or as an ointment (Optimmune®).

Substitution of tears is achieved by combination of individual tear components. There is a number of "artificial tears" on the Czech market. Their selection depends on the dog's clinical condition, local tolerance, price, and level of collaboration with the animal owner. Methylcellulose and hydroxyethylcellulose (AquaSite CIBA Vision) are the most frequently used corneal lubricants due to their good local tolerance and easy combinations with other preparations. Other frequently used substitutions of tears are polyvinyl alcohol in 1.4% solution (HypoTears, Ciba Vision, Bion Tears Alcon), furthermore linear polymers such as dextrane a polyvinylpyrrolidone (Tear Plus, Allergan), or viscose-elastic preparations such as hyaluronate sodium (Healon, Pharmacia Upjohn), chondroitine sulfate or high concentrated methylcellulose or ophthalmologic lubricants such as lanoline, petrolatum or mineral oils (Lacri-Lube, Allergan, Lacrisyn Galena).

Broad-spectrum antibiotics are successfully used as eye drops or ointments in order to suppress secondary infections. Bacteriological examinations are rarely necessary. Usually, combinations of bacitracin--neomycin--polymyxin B are recommended.

An adequate hygiene of the eyes is inevitable. A usage of 5-10% solution of acetylcysteine is a useful complementary therapy of corneal ulcers.

Antiinflammatory drugs used in our country are in indicated cases topical corticosteroids, in order to reduce conjunctivitis and clear corneal opacities in chronic keratitis (fluorescein test must be negative). Their usage is contraindicated in chronic conditions and in corneal ulcers. As KCS is frequently associated with autoimmune diseases, also systemic corticosteroids can be used. Topical vitamin A can be added to the therapy.

Surgical therapy of KCS: In indicated cases, permanent partial lateral tarsorrhaphy, temporary protection of corneal ulcerations with nictitating membrane or transposition of parotid duct can be done.

Surgical approach in the treatment of KCS i.e., transposition of the parotid duct is always the last option when all other methods fail. This method is mostly applied after a treatment with cyclosporin, when no improvement of tear production is observed after 8-9 weeks (STT test).

This method assumes that tears and saliva have similar characteristics in terms of pH and osmolarity.

There are two approaches to transposition: occluded (buccal- closed) approach and open (lateral) approach. In our clinic, we routinely use the buccal approach, because it is more comfortable for the animal owner. He does not need to observe his pet too closely, in order to prevent auto mutilation. Otherwise both approaches are equal in the results and their selection depends on the surgeon's preference.

Potential complications: Using either method, it is important to avoid any damage to salivary papilla or torsion of the salivary duct. Salivary duct has to be long enough, in order to prevent any tension during chewing. One of the noteworthy complications is a closure of the salivary duct at the entrance into the conjunctival sac--mostly caused by retraction of the salivary duct. Obstructions of the salivary duct were also occasionally reported--either as a result of sialolithiasis or inflammatory processes (sialoadenitis). A frequent observation in patients with high concentrations of minerals in the saliva is their deposition on the corneal surface and palpebral rims. The precipitates can be easily removed by using artificial tears or other lubricants. Another potential complication that needs to be communicated to the pet owner is maceration and discoloration of skin in the medial eye angle, when the fluid is insufficiently drained through puncta lacrima. We can use ointment before feeding to protect skin.

In brachycephalic breeds, additional reduction of the palpebral fissura contributes to spreading of the tear film across cornea and prevents development of chronic central keratitis associated with pigment deposition in the upper corneal layers. A recommended method is Roberts-Jones pocket technique.

Summary: KCS is long term disease. We can threat in 90% topically using long term cyclosporine. When we don't have success therapy after 8 weeks, it is time to start surgery. We prefer buccal approach but it is necessary to explain to the owner all potential complications and side effects. Surgery is the best result for busy owners as well /they don't have enough time to use drops or ointment topically.

Speaker Information
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Jiri Beranek, DVM
Veterinary Clinic
Pardubice, Pardubický kraj, Czech Republic

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