What is the Normal Physiology and Anatomy of the Tear Film?

Tears are a trilaminar structure which when produced in adequate quantity and quality enable the cornea to stay clear. The tear film has three layers, an innermost mucin layer, a middle aqueous layer and an outer lipid layer. The mucin and lipid layer constitute about 30% of the tear film, while the aqueous component constitutes about 70 % of the tear film. The mucin layer is produced by conjunctival goblet cells. The aqueous component is primarily produced by the dorsolaterally placed lacrimal gland, with a smaller amount, about 30%, produced from the gland of the third eyelid. The lipid component is derived from Meibomian glands. This lipid component is called Meibum, a form of modified sebum.

Each of the layers of the trilaminar tear film plays an essential role in normal corneal health. The mucin acts to smooth out the epithelial surface, as well as binding the aqueous component of the tear film to the hydrophobic epithelium. The aqueous component of the tear film maintains ocular health by amongst other things purging the cornea of debris, and also providing various antibacterial substances such as secretory IgA and lactoferrin. The outermost component of the tear film is the lipid layer or Meibum. This fatty layer provides a slick coating over the aqueous layer to minimize the amount of dehydration of the tears.

What is Dry Eye?

Dry eye or keratoconjunctivitis sicca (KCS), is a condition in which there is not enough tears produced in the eye. Usually when referring to KCS we are in fact referring to a lack of the aqueous component of the tear film. This is termed a quantitative tear film deficiency. A deficiency of either of the other components of the tear film, i.e., the mucin or lipid layer may also affect corneal health, and is termed a qualitative tear film deficiency.

There are situations in which whilst there may be adequate tear production, and quality, the tear film itself is poorly distributed across the cornea. The end result is still the same as a quantitative dry eye i.e., there are parts of the cornea with inadequate tear coverage and protection. The most common situation that this is seen in is with brachycephalic type dogs. In these dogs the horizontal axis of the cornea is inadequately covered by the eyelids. This results in pathology of the cornea such as keratitis and pigmentation typically seen with KCS due to a lack of tear production itself. Other causes of poor tear film coverage may include facial nerve paralysis, tick paralysis and animals under ketamine anaesthesia.

How Does the Cornea React to Damage Caused by KCS?

The first stage of dry eye is dehydration and subsequent hypertonicity of the corneal and conjunctival epithelial cells. The anterior surface of the cornea rapidly becomes hypoxic. The lack of ocular lubrication causes frictional damage by the eyelids and the third eyelid as they slide over the corneal and conjunctival surfaces. Metabolites from the cornea and conjunctiva can build up and these may further cause injury to these tissues. The inflammatory process can cause squamous metaplasia of the conjunctival epithelium, which causes loss of the mucin producing goblet cells, and ends up causing further tear quality problems.

The cornea reacts in a fairly predictable way for an epithelialized structure. Initially there is oedema, then with chronicity blood vessel ingrowth and subsequent pigmentation occur. These changes are typical of the damage seen with KCS.

What Causes KCS?

The vast majority of KCS cases are caused by the body's own immune system i.e., an autoimmune disease directed against the lacrimal gland. Work done in the early 1980s showed that there was a strong mononuclear cell infiltrate of lymphocytes and plasma cells into the lacrimal gland suggesting an autoimmune basis.

There also seems to be a strong breed predilection for dry eye. Breeds predisposed include Bull terriers, Cocker Spaniels, English Bull dogs, Cavalier King Charles Spaniels. Lhasa Apsos, Shih Tzus and West Highland White Terriers amongst other breeds.

Other Causes of Dry Eye Include

 Blepharitis

 Canine distemper virus

 Congenital gland hypoplasia / aplasia

 Conjunctivitis--chronic

 Drug induced, such as with sulpha drugs--Tribrissen, Salizopyrines

 Topical Atropine

 Endocrine

 Hypothyroidism

 Diabetes

 Cushing's disease

 Facial nerve paralysis

 Immune mediated disease against the lacrimal glands--most common cause

 Neurogenic

 Orbital disease

 Third eyelid gland prolapse with surgical excision of a cherry eye or failure to treat a cherry eye

 Trigeminal nerve paralysis

What are the Clinical Signs of KCS?

The clinical signs of KCS include squinting, copious amounts of thick discharge from one or both eyes (often both are affected), conjunctivitis, corneal oedema, keratitis, and pigmentation and blindness. In some cases having a dry nose can also be seen too.

Diagnosis of Dry Eye?

The Schirmer Tear Test (STT) remains the gold standard for the diagnosis of KCS. There are 2 types of STT. The STT I test is done without local anaesthetic, and therefore measures both the basal and reflex components of the tear film. In the STT II test topical anaesthetic is applied so the STT II will only measure the basal component of the tear film. The STT I and the STT II in the dog are quite different. For nearly all cases the STT I is performed in Veterinary Practice.

In veterinary practice, Schirmer Tear Test strips can be used to measure tear production. STT strips that are printed with millimeters on them, and are impregnated with a blue dye so it stains the tears as they advance up to the STT strip. This greatly facilitates tear measurement.

Evaluating the STT

As a general rule of thumb, normal STT values should be 15-25 mm/minute. It has been suggested that 11-14 mm/min is suggestive of early KCS, while 6-10 mm/min is moderate KCS and less than 5 mm/minute is severe KCS. In my opinion these values have to be interpreted in light of other clinical signs. For example, animals that have 10 mm/min in the absence of clinical signs may not need treatment but at the very least should be monitored.

Treatment of KCS

Treatment for dry eye can be either medical or surgical. Fortunately most animals respond well to medical therapy. The basis for treatment involves stimulating any remaining lacrimal tissue, using tear substitutes until such time as the tear production returns to normal--if in fact it does, and control of the secondary changes associated with KCS such as overgrowth of flora and the accumulation of mucopurulent discharge.

Cyclosporine is one of a number of drugs now used to combat the autoimmune component of KCS. It may work in two ways--one is hormonal related and occurs in the first few days. The other is immune related and works by changing the ratio of T helper to T suppressor cells in the lacrimal glands. This effect may take 2-3 months to occur. Other similar drugs now being used include tacrolimus and pimecrolimus. Therefore treatment with cyclosporine should continue for at least 3 months before deciding on its efficacy or otherwise. At that time I tend to use tacrolimus in cases unresponsive to cyclosporine.

There are 3 basic categories of artificial tears, polyvinyl alcohols--which adhere well to the cornea, cellulose derivatives--which are more viscous than other preparations, and linear polymers. These polymers are often combined with cellulose products. They are useful as they have mucinomimetic properties, and with the cellulose are useful to treat both quantitive as well as qualitative dry eye conditions. Probably the important thing to remember with using these medications is that at best they will stay on the cornea for 1-2 hours, with some of the less viscous products only staying on for a few minutes. Therefore frequent application is required.

Other medical treatments that have been used in the past include oral pilocarpine for its parasympathomimetic effects and topical corticosteroids in the absence of corneal ulceration. In my experience both of these therapies can be used as an adjunct to the abovementioned medications. In addition basic ocular hygiene should not be forgotten, such as keeping the hair short around the eyes, and bathing the eyes 2-3 times daily with a warm water compress to remove crusts that may accumulate.

Surgical options may sometimes be pursued. For cases due to a failure of tear distribution, such as in brachycephalics, surgical intervention is needed to decrease corneal exposure. This may include some form of temporary or permanent tarsorrhaphy. In other cases of KCS refractory to medical therapy a parotid duct transposition can be considered. Parotid ducts transpositions may improve the clinical signs of pain in about 80% of cases (Robin Stanley pers. comm.), but in certain circumstances further surgery to decrease the amount of fluid produced may be necessary.

References

1.  Veterinary Ophthalmology, 4th Ed, 2007. Edited by Dr Kirk Gelatt.