The term keratoconjunctivitis sicca (dry eye) is used to describe insufficient production of the aqueous component of the tear film, which causes inflammation of the conjunctiva and cornea with extremely heterogeneous signs.
SIGNS
The signs of keratoconjunctivitis sicca are varied and depend mainly on how long the disorder, which can be unilateral or bilateral, has been present. The associated inflammation often gives rise to blepharospasm with or without secondary protrusion of the third eyelid. The presence of mucus or mucopurulent material adhered to the conjunctiva and, in some cases, also to the cornea and palpebra is a common clinical sign of the disorder (Fig. 1). During blepharitis secondary to keratoconjunctivitis sicca the eyelids can be thickened and red and often there is also a periocular dermatitis. Variable degrees of conjunctival oedema, thickening and hyperaemia are common. The cornea tends to lose its natural transparency with the development of oedema, superficial and deep neovascularisation and, in the chronic forms, widespread pigmentation (Fig. 2). A frequent complication of keratoconjunctivitis sicca involving the cornea is the development of secondary corneal ulcers. In the case of ipsilateral dryness of the nasal mucous membrane (xeromicteria) a neurogenic cause of the keratoconjunctivitis sicca, with altered innervation of the glands of the ipsilateral nasal mucosa, should be suspected (Fig. 3)
Fig. 1 Fig. 2 Fig. 3
AETIOLOGY
There are numerous causes of keratoconjunctivitis sicca. Very often the disorder is related to a local or systemic immune-mediated process in which the epithelial cells of the lacrimal gland are damaged by inflammation. In some cases animals with immune-mediated keratoconjunctivitis sicca may have other disorders of the same aetiological basis such as Sjogren’s syndrome or atopy. Some metabolic disorders, including hypothyroidism, diabetes mellitus and hypercortisolism, can cause insufficient production of tears. Other forms can be drug-induced; the main drugs involved are etodolac (a non-steroidal anti-inflammatory drug), and some sulphonamide derivatives such as trimethoprim-sulphamethoxazole, sulphadiazine, 5-aminosalicylic acid and sulphasalazine. Phenazopyridine (the active principle of an analgesic used for urinary disturbances), topically or systemically administered atropine, and many anaesthetics and premedications can contribute to underproduction of tears. There are also some iatrogenic causes of insufficient tear production, such as removal of the gland of a prolapsed third eyelid or lesions to the facial nerve during middle ear surgery. The infective causes include canine distemper virus, infection by Leishmania in the dog, Herpesvirus in the cat and all the virally and bacterially based chronic forms of conjunctivitis and blepharoconjunctivitis. Some breeds, including the pug, Chihuahua and Yorkshire terrier may have a congenital form related to hypoplasia of the lacrimal gland; in these cases the keratoconjunctivitis can be unilateral.
There is also a predisposition in some breeds and a genetic basis to this predisposition has been suspected in some cases.
Dog breeds predisposed to the development of keratoconjunctivitis sicca
- Bloodhound
- Boston terrier
- English bulldog
- Pug
- Cavalier King Charles spaniel
- English and American cocker spaniel
- Lhasa Apso
- Pekingese
- Samoyed
- Miniature schnauzer
- Shih Tzu
- English Springer spaniel
- Yorkshire terrier
- West Highland white terrier
Animals receiving radiation treatment to the head may develop lesions of the main and accessory lacrimal glands. In elderly animals the disorder may occur following senile atrophy of the gland. Neurogenic keratoconjunctivitis sicca can occur in the case of damage to the parasympathetic innervation of the lacrimal gland (VII cranial nerve), involvement of the trigeminal nerve and dysautonomia. Orbital or supraorbital trauma can directly damage the gland or its afferent nerves.
DIAGNOSIS
The diagnosis of keratoconjunctivitis sicca can be made from a precise history, observation of the clinical signs and measurement of the aqueous content of the tear film using Schirmer’s test. The values of this test must be interpreted with care, but values of 10 mm/min or below are strongly indicative of keratoconjunctivitis sicca. The use of stains such as rose Bengal and fluorescein can demonstrate the presence of devitalised epithelial cells, mucus, very slight defects of the corneal surface (rose Bengal) and ulcers, shown by the uptake of dye (fluorescein) by the corneal stroma which is no longer protected by overlying epithelium. The phenol red thread test can also be used for diagnostic purposes: in this test a fine thread soaked in the coloured dye is placed in the ventral conjunctival fornix. The result is read after 15 seconds: values between 30 and 38 mm are considered normal.
TREATMENT
Keratoconjunctivitis sicca can be managed medically or surgically. Surgery is usually performed only when all attempts at medical treatment have failed or given unsatisfactory results, in aggressive subjects or when the animal’s owner has difficulty in administering the treatment for any reason.
Medical treatment
Medical treatment of keratoconjunctivitis sicca has the following purposes:
A) to stimulate tear production;
B) to replace the tear film;
C) to control the inflammation of the cornea and conjunctiva;
D) to provide an antibacterial effect;
E) to eliminate the mucus that deposits on the surface of the eye.
Drugs stimulating the production of tears
The current drug of choice for the local treatment of keratoconjunctivitis sicca is cyclosporine A, commercially available in ointments at a concentration of 0.2% or in galenic preparations in olive oil or corn oil at a concentration of 1.0% or 2.0%. Besides stimulating the production of the aqueous component of the tear film by the main lacrimal gland and the accessory lacrimal gland, cyclosporine also tends to reduce the corneal pigmentation and has a positive effect on the secretion of mucus from the muciparous goblet cells. The drug is administered as a drop of collirium or an application of ointment every 12 hours. Another compound that is used in cases in which cyclosporine is ineffective is tacrolimus. Unfortunately the risk of negative side effects associated with this drug and its potential carcinogenicity limit its use. In patients with keratoconjunctivitis sicca of a neurological basis (parasympathetic denervation), pilocarpine, administered locally or orally together with food, is often the treatment of choice. The starting dose for oral therapy could be one drop of pilocarpine 2% every 10 kg of body weight twice daily; the dose should then be increased by one drop every 2 or 3 days while monitoring systemic signs of its toxicity (loss of appetite, sialorrhoea, vomiting, diarrhoea, bradycardia). Precisely because of its potential toxicity, the drug must be used cautiously and only under the careful control of a veterinarian. Another active principle used, similar to tacrolimus, is pimecrolimus.
Tear film substitutes (artificial tears)
Drugs used to replace the tear film must have the following characteristics:
- Lack of irritant effect on the eye;
- Good lubricating action, surfactant, mucomimetic and lipid replacement properties;
- Sufficiently long retention time;
- Lack of effect on vision.
The most commonly used active principles include the cellulose ethers (carboxymethyl cellulose, methylcellulose, hydroxypropyl methylcellulose and hydroxyethylcellulose), mucopolysaccharides (hyaluronic acid) and synthetic polymers such as polyvinyl alcohol, polyethylene glycol (macrogol), polyoxyethylene propylene glycol (poloxamer), polyacrylic acid (carbopol), and polyvidone (polyvinylpyrrolidone). Ointments based on lanoline, paraffin, petroleum jelly or vaseline can be applied with the purpose of decreasing the evaporation of the tear film and lubricating the ocular surface. These products do, however, have the disadvantage of increasing deposits of material at the edge of the eyelids, contributing to increasing the animal’s discomfort. The most frequent problem encountered with prolonged use of artificial tears is hypersensitivity related to the presence of preservatives in the products used (see box). This problem can be avoided by using individually packaged single doses not containing preservatives.
Anti-inflammatory drugs
Topical use of dexamethasone 0.1% or prednisolone 1% is recommended in order to reduce inflammation, the consequent neovascularisation and secondary pigmentation of the corneal surface. Alternatives to corticosteroids are non-steroidal anti-inflammatory drugs such as flurbiprofen, indomethacin and diclofenac. These products should be administered at least 3-4 times daily. Both classes of anti-inflammatory drugs must be used with caution if the presence of corneal ulcers is suspected because they can activate enzymes capable of breaking down collagen.
Antibacterial drugs
The use of antibiotics is advised when there is a secondary infection of the ocular surface. Corneal cytology and corneal-conjunctival swabs to isolate any micro-organisms, with possible testing in an antibiogram, is the strategy of choice in order to choose the correct drug treatment. However, while waiting for the results of the laboratory investigations, tobramycin, quinolones or chloramphenicol may be useful. Also in this case the drugs must be given at least every 6-8 hours.
Mucolytic drugs
The owner of an animal with keratoconjunctivitis sicca must remove any mucus or mucopurulent material that accumulates on the surfaces of the eyelids, conjunctiva and cornea. The excess mucus produced by muciparous cells can be removed using physiological saline in association with acetylcysteine 5%, a substance with a mucolytic effect.
Surgical treatment
Surgical treatment involves transposition of the parotid duct or isolation and deviation of the duct of the parotid salivary gland to the conjunctival sac so that the salivary secretion lubricates the surface of the cornea and conjunctiva.
Suggested readings
- Carter R,Colitz CMH. The causes,diagnosis and treatment of canine keratoconjunctivitis sicca. Vet Med 2002;97:683-694.
- Helper LC.The tear film in the dog.Causes and treatment of the diseases associated with overproduction and underproduction of tears. Animal Eye Res.1996;15:5-11.
- Severin GA. Keratoconjunctivitis sicca. Vet Clin North Am 1973;3:407-422.
- Klauss G, Giuliano EA, Moore CP, Stuhr CM, Martin SL, Tyler JW, Fitzgerald KE, Crawford DA. Keratoconjunctivitis sicca associated with administration of etodolac in dogs: 211 cases (1992-2002). J Am Vet Med Assoc. 2007 Feb 15;230(4):541-7.
- Stiles J.Warning of an adverse effect of etodolac. J Am Vet Med Assoc. 2004 Aug 15;225(4):503.
- Slatter D. Disease and surgery of the Lacrimal secretory system. In: Slatter D, ed. Fundamentals of Veterinary Ophthalmology. 4rd ed. Philadelphia: Saunders WB. 007: 618-661.