Dry Eye: One Disease Or Many?
Duane Flemming, DVM, JD
Keratoconjunctivitis sicca, xerophthalmia, or dry eye is a common problem in the dog and tends to be a rather rare problem in the cat. In fact, canine dry eye cases make up almost 25% of my practice volume while feline dry eye accounts for less than 1%.
For all land based mammals, tears are a critical factor in servicing and protecting the eye. Tears maintain the optical quality of the eye, nourish the cornea, cleanse and lubricate the eye, and provide some level of immune and antibacterial protection. The tear film is comprised of three components: 1) a thin outer oily layer secreted by the Meibomian Glands, 2) a middle aqueous layer secreted by the primary and nictitans tear glands, and 3) a thick inner mucin layer secreted by the conjunctival goblet cells and perhaps, to some degree, by the conjunctival epithelium. Dry eye occurs because one or more of the lacrimal secreting components has failed.
The clinical signs of dry eye are dependent upon the stage and underlying cause of the disease. In early cases, the lack of adequate corneal lubrication causes a sensation, described by people with dry eye, as one of sand or grit in the eye. In dogs and cats this is manifest as a slight enophthalmos and often as an intermittent rapid blinking or squint. This sign is frequently overlooked by both owners and veterinarians.
As the disease progresses, in aqueous deficient dry eyes, the lack of liquid tears will cause a gradual increase in ocular and non-ocular debris along with an increase in mucin production. This additional mucin and cellular debris create the sticky material generally described as excess mucus. In most dogs with severe dry eye the mucus will accumulate on the eyelids, within the conjunctival fornices, and even across the corneal surfaces. Because of the natural circadian rhythms of tear production, this discharge will often will be worse in the mornings and less dramatic in the afternoons. This material is often mistaken for a severe conjunctival infection. Although some dry eyes have a bacterial component, many are sterile. Dry eye mucus can usually be distinguished from infectious pus by its thick, tenacious nature. In Mucin-deficient dry eyes, the excess mucus component does not develop. Despite use of the term “dry eye”, these dogs will frequently show excess aqueous tearing. In dogs with neurological dry eye, the external nares on the affected side will be covered and sometimes plugged up with excess mucus.
Despite the underlying cause, the corneal epithelial cells deprived of adequate moisture will eventually begin to degenerate and the ocular defense mechanisms will begin to kick in. First, the limbal blood vessels start to grow across the cornea. Then, in most dogs and very few cats, the pigmented limbal conjunctival cells will also begin to migrate across the cornea. In chronic dry eyes, the vessels and pigment can completely cover the cornea producing diminished vision and even blindness. If left without treatment for long enough, the chronically dry cornea can begin to look and feel just like the foot pads. In those animals with minimal to no conjunctival pigment, there will be no corneal pigmentation. However, a strong vascular response can render those animals nearly as blind.
In most animals with dry eyes the conjunctival tissues are hyperemic and, depending on the severity and chronicity of the condition, usually somewhat thickened. Unless there are concurrent neurological conditions, the external eyelids and intraocular contents are seldom affected by clinical dry eye.
Besides a proper evaluation of the clinical signs, the best way to diagnose or, for that matter, to rule out dry eye is the Schirmer Tear Test. The Schirmer Tear Test is done with a 5 x 30 mm of notched filter paper standardized to absorb fluids at a specific rate. The paper strip is folded at the notch and inserted over the eyelid into the lower conjunctival fornix. The ocular portion of the strip should be in contact with the cornea. The paper strip is left in place for one minute. The wetted portion is immediately read or measured. Schirmer Tear Test readings of less than 10 mm in the dog will usually confirm a clinical dry eye. Readings of 10-15 mm/min are suspicious and readings of 15-25 mm/min are normal. Animals with other clinical signs of dry eye and tear test readings of greater than 20 mm/min should be suspected of mucin-deficiencies.
Rose Bengal is a vital stain that stains cells in the early stages of degeneration. Sub-clinical dry eye creates in situ but degenerative epithelial cells. Rose Bengal can help identify these degenerative cells before the more severe clinical signs of vascularization and pigmentation are apparent. While not pathognomonic for dry eye, some ophthalmologists feel Rose Bengal may be valuable in identifying early cases of dry eye.
Tear Break Up Time (TBUT): The mucin layer acts as a hydrophilic interface between the hydrophobic corneal epithelium and the aqueous tear layer and creates a smooth optical surface free of particulate debris. In between blinks the mucus layer disorganizes and the tear film becomes unstable. In the dog, a normal mucin layer will maintain an intact tear film for 15-23 seconds. Two drops of fluorescein stain are placed in the ventral conjunctival fornix of each eye. The eye(s) are manually blinked 2-3 times then held apart. A Black Light or Cobalt Blue filtered light is then used to observe the cornea. The TBUT represents the time between the last blink and the first spot of tear film disruption. If the TBUT is significantly less than 15 seconds there may be a mucin deficiency.
BACTERIAL CULTURE: All animals with chronic conjunctivitis of any kind should be examined for bacterial infections. When positive for bacterial growth, most dry eye animals will show Staphyloccocus or Streptococcus although almost anything will grow in a compromised eye.
FLUORESCEIN DYE: Some animals with corneal ulcers have diminished tear production or even frank dry eye. Conversely, many animals with dry eyes have superficial or deep corneal ulcers. Fluorescein Dye staining should be done in all cases of suspected dry eye to determine the presence of ulcers. In addition, most animals with dry eye will show mild diffuse punctate staining over some portion of the cornea. In my opinion, this specific staining pattern is always evidence of superficial corneal damage and is at least suggestive of a dry eye.
CAUSES OF DRY EYE
Congenital alacrima is occasionally seen in small breed dogs (Pugs, Pekingese, Yorkshire Terriers, and Chihuahuas) or cats. Most are unilateral but bilateral cases can be encountered. These animals will usually not respond well to medical therapy necessitating eventual Parotid Duct Transposition.
Immune-Mediated Autoimmune Dacryoadenitis is the most common cause of dry eye in the dog and affects approximately 70-80% of the cases seen. Although a wide variety of breeds can be affected, only a few breeds (Cocker Spaniels, Lhasa Apso, Shih Tzu, English Bulldogs, Miniature Schnauzers) are statistically predisposed to this form of dry eye. In these cases, the lacrimal glands are infiltrated with mononuclear cells and show varied degrees of fibrosis and eventually glandular atrophy. Many of these animals will show a positive Rheumatoid Factor or Anti-Nuclear Antibody test. As an immunosuppressant drug, Cyclosporine is most effective in immune-mediated dry eyes.
These animals often show signs of other autoimmune diseases. Hypothyroidism, hyperadrenocorticism and immune-mediated dermatoses are common. Some animals may also be affected with rheumatoid arthritis and occasionally systemic lupus erythematosis is encountered.
Paralytic lacrimal hyposecretion may occur with lesions of Cranial Nerves V and/or VII. Trigeminal lesions are usually traumatic or idiopathic in origin although in cats viral infections may result in dry eye. Diabetics show decreased sensitivity that occasionally develops into a clinical dry eye. Lesions of the seventh cranial nerve leading to dry eye may result from trauma, otitis media/interna, nasopharyngeal tumors, or other CNS lesions. Horner’s Syndrome is often associated with seventh nerve disease especially when it is related to otitis media/interna.
Pharmacological Lacrimal hyposecretion and even clinical dry eye can be brought on by a variety of drugs. Atropine, phenazopyridine (Azogantrisin), sulfadiazine(Suladyne), salicylazosulfapyridine (Azulfidine), and etodolac (Etogesic) have all been associated with dry eye in the dog.
Idiopathic Dy Eye is seen in large breeds ( German Shepherds and Rhodesian Ridgebacks) and is often severe and non-responsive. Medical therapy rarely is effective and Parotid Duct Transposition is usually necessary.
Neutered animals of all breeds are statistically more likely to develop dry eye. Estrogen deficiency has been associated with mucin deficiencies in the Shetland Sheepdog.
Cherry Eye: Several studies have shown that dogs whose nictitans glands have been removed have an increased incidence of dry eye. Other studies have shown that, in a normal dog, dry eye cannot be created by removing the nictitans gland. It seems that many of the breeds subject to prolapse of the nictitans gland are also subject to the later development of dry eye (Cocker Spaniels, English Bulldogs). In those breeds, or in dogs with marginal tear production, it would be wise to replace the nictitans gland if possible and to remove it only if necessary for the health of the dog.
Lipid deficiencies: Animals with chronic blepharitis and those with chronic blepharoconjunctivitis may, in addition to their eyelid problem be subject to a rare form of dry eye. These animals show the same squinting behaviors as normal dry eye dogs. They share the conjunctival hyperemia but do not show excess mucus production. The tear loss is believed to be from excessively rapid evaporation of the aqueous tears resulting from diminished lipid secretion from the Meibomian Glands. Tear replacement therapy supplemented by Cyclosporine Ointment can be very effective in these cases.
Artificial Tear Substitutes: There are a great variety of artificial tears available for the treatment of lacrimal hyposecretion or dry eye. Most are made of methycellulose or polyvinyl alcohol and are used to increase surface tension and to retard evaporation. These products have short contact time in the eye and while they do increase TBUT, the long blink interval in the dog limits their use. To be really effective, the liquid tear preparations must be used very frequently, perhaps as often as every 15-30 minutes. Artificial Tear Ointments (LacriLube and others) show increased contact time in the eye and, therefore, can be applied less often.
Cyclosporine is an immunosuppressive drug normally used in humans after organ transplantation to reduce the rejection reaction. Cyclosporine works against dry eye, in part, by penetrating the lacrimal gland and suppressing T- helper cells and reducing local immune responses. Cyclosporine may also help dry eyes by reducing corneal epithelial proliferation and decreasing superficial corneal pigmentation.
Pilocarpine acts as by direct parasympathomimetic stimulation of the lacrimal and nasal gland cells normally innervated by post-ganglionic neurons. It is most helpful in animals with paralytic or neurological lacrimal hyposecretion. In those animals adequate doses of Pilocarpine can increase tear flow within one hour and the effect can last for up to 12 hours. Although Pilocarpine can be given topically, orally or by injection, the most effective and convenient route is oral. Because the effective dose level differs in individual animals the drug must be titrated to effect. A medium sized Cocker Spaniel will often show a good response to 3-4 drops of 2% Pilocarpine given, by mouth, every 12 hours. The most common adverse side effect is hypersalivation but vomiting, diarrhea and occasionally bradycardia can be encountered.
Parotid Duct Transposition (PDT): When medical therapy is inadequate or ineffective in replacing the missing tears surgical intervention may be indicated. Despite some claims to the contrary, PDT is, in my opinion, a very effective surgical treatment for clinical dry eye. The procedure involves the movement or transposition of the parotid salivary duct from the oral mucosa to the ventral conjunctival sac. The parotid secretions then flow over the eye. While the parotid secretions are not exactly the same as tears they do make a more than adequate, if not ideal, substitute for the missing tears. Parotid secretions flow at a higher rate than tears which may leave the animal with a wet face. Occasionally, the secretions may be excessive necessitating partial resection of the parotid gland, surgical stenosis of the duct or medical therapy (propantheline bromide- Probanthine) to decrease flow. In some animals the parotid secretions are high in Calcium resulting in mineral deposits on the eyelids and corneas. These can be minimized with compounded Na or K-EDTA drops.