DRY EYE: EMERGING OPHTHALMIC PROBLEM

DR. M. R. JAIN M.S, FICS ( USA), FACLP ( London ) FAMS
MEDICAL DIRECTOR
M. R. J INSTITUTE AND JAIN EYE HOSPITAL, JAIPUR

Dry eye is the most frequent disorder in Ophthalmology. Fortunately, only infrequently it becomes the most severe. Although the condition was recognized as a clinical disorder in the year 1920 and described clinically in the early 1930’s, the greatest amount of information both from an epidemiological and pathogenetic perspective has accrued during the last ten years.

What is dry eye?

Dry eye is a disorder of the preocular tearfilm that results in damage to the ocular surface and is associated with symptoms of ocular discomfort. Dry eye is characterized by instability of the tearfilm that can be due to insufficient amount of tear production or due to poor quality of tearfilm, which results in increased evaporation of the tears.
Dry eye therefore can be divided in two groups, namely
1. Aqueous production deficient
2. Evaporative

Prevalence of dry eye.

No authentic prevalence survey has been conducted in India but it is noted that out of the patients above the age of 30 years attending the outdoor, one out of every five has a complaint pertaining to dry eye. A recent survey conducted in year 2002, based upon a well – characterized population of adult men and women in the USA, identified a prevalence of 6.7 percent in women over the age of 50 and 2.3 % in men over the age of 55.These rates extrapolate to potentially 9.1 million dry eye patients in USA alone.
In women at the age of 50-52 when menopause usually sets in, an imbalance occurs between the oestrogen and androgen hormone due to decrease of androgens after the menopause. Decrease in androgen levels, excites inflammation in lacrimal gland and ocular surface, disrupting the normal homeostatic maintenance of the lacrimal gland and ocular surface.
The factors which has increased the incidence of dry eye can be narrated as under
a. increasing longitivity of the population
b.increased consumption of medication, both systemically and topically which have adverse effect on the production of high quality of tears
c. increased computer use
d. increased contact lens use and cosmetic surgery of LASIK/ LASEK
e better understanding and diagnosis of dry eye.
f possibly, adulteration in the food?

Pathogenesis of Dry Eye

It is an established fact that any lacrimal gland damage would result in decreased tear flow. This leads to decreased washout of the tear surface debris and bacterias as well as increased presence of inflammatory cytokines and decreased growth factors to maintain ocular surface integrity.
Almost all tear flow is due to a reflex mechanism due to stimuli from cornea sending impulses to the brain and to the lacrimal gland. Any thing which disturbs corneal sensations like hormonal imbalance, contact lenses, LASIK surgery or any other trauma to the eye, may it be surgical or accidental.

The aqueous deficient dry eye (keratoconjunctivitis sicca) is a disturbance of the neuro-humoral interaction of the ocular surface which interrupt secretomotor nerve impulses to the lacrimal gland that results in inflammatory suppression of aqueous secretion, a necessary component of the tearfilm, with subsequent damage to the ocular surface, producing symptoms of ocular irritation and discomfort. The evaporative dry eye is a disturbance of the stability of the tearfilm, which is usually due to abnormalities of Meibomian gland secretion or abnormal eyelid position and movement. Both types of dry eye results in damage to the ocular surface and symptoms of ocular discomfort and impaired visual function.

Tear Film
It comprises of three layers
Outer Lipid layer
It is formed by the oily secretion of Meibomian glands. It acts as a lubricant and prevent evaporation of tears.
Middle Aqueous Layer
It is the main tear fluid liberated from lacrimal gland and Accessory glands. It contains proteins, immunoglobulins, lysozyme, lactoferin and betalycin. It provides moisture to the eye, nutrition to the cornea and antibacterial activity. It provides the epithelial cells with glucose, oxygen and growth factors. It flushes out the debris and organisms from the corneal surface and drains into nasolacrimal canal.
Inner Mucous Layer
The innermost mucous layer of the tear film forms a highly hydrophilic wetting surface over the hydrophobic epithelial surface of the cornea and conjunctiva. The mucous also reduces the surface tension between the lipid layer of the tear film and the water layer, thus contributing to the stability of the tear film.

Classification Based On Etiology

1. Age Related. Lacrimal secretion begins to decrease after the age of 30 years. At the age of 6o, we reach the borderline between the production and need. At the age of 90, almost all persons have dry eye.
2. Hormonal. At the age of menopause almost every women develops dry eye either mild or moderate. Recent research has shown that it is due to lowering of androgen levels produced by the ovaries. Men develop dry eye related to hormones with less frequency and intensity than women.
3. Pharmacological. There is adverse effect on production of tears due to preservatives in teardrops used for long period. Glaucoma patients are more prone to this problem due to prolonged therapy.
Systemic drugs like antidepressants, antihypertensives, antihistaminics, anticholinergics, antipsychotics, angiolytics, antiparkinsonians, diuretics and hormones too can cause dry eye.

4. Immunological: This is related to autoimmune reaction in exocrine glands affecting outside body secretion like secretion of tears, saliva, sweat and vaginal secretions. The Sjogren’s syndromes are those in which patient’s immunological system attacks its own exocrine glands. Rheumatism, cicatricial pemphigoid and erythema multiform can lead to Sjogren’s syndrome.
5. Infection. Chronic infection of conjunctiva can affect mucous secretion leading to mucin deficiency and infection of lacrimal glands can affect aqueous secretion. Inflammation of lids may affect oily secretion. Any of the component if affected, tearfilm is disturbed.
6. Hypo nutrition. Avitaminosis A, and alcoholism that leads to poor intestinal absorption may give rise to dry eye.
7. Traumatic: Any trauma to the eye may it be accidental or surgical, can precipitate dry eye. Major surgeries like removal of tumour etc has more chances to cause dry eye. Cataract or glaucoma surgery too can be responsible especially in older persons.
8. Neurological.
a. Post LASIK. Lasik leads to the development of temporary dry eye in about 4 percent of patients. The Lasik induced dry eye tends to resolve approximately within 6 months.

b. Contact lens wear. Contact lenses when worn for prolonged period, affect corneal sensations and hence decrease tear secretion.
9. Defective glands. Responsible for aqueous, mucin and lipid secretions.
10. Inability to utilize tears. There is normal production of tears but cornea is unable to use them due to:
a. Epitheliopathy or corneal dystrophy, which decreases corneal, wet ability.
b. Due to lipid defect the lids are unable to circulate the tears over the entire ocular surface (lid paralysis, ectropion, lagophthalmos)
Symptoms
Dry eye patient can present any one of them or multiple symptoms:
Itching, burning, irritation, pain, discomfort. There may be pain and photophobia and blurred vision that improves with blinking. There is usually stringy ropy mucous discharge, which can increase in the afternoon. The discomfort in the eye usually increases while reading, watching T.V or working on the computer. At times there may be excess of watering, specially during breeze.
All these symptoms are exaggerated during dry and windy conditions.
Some of the patients give a typical history of desire to frequently sprinkle water into the eyes.
Signs

Tear Lake. Normally at the lower lid margin there is there is concave tear meniscus of 0.3 to 0.5 mm, which is called Tear Lake. In dry eye it is usually less than 0.1mm.
Debris. There is increased debris in the decreased tear lake. Mucous threads may be seen.
Other Signs. Redundant conjunctiva, injection of the conjunctival vessels, and sometimes mild chemosis may be present. In advanced cases, the conjunctival and corneal dryness may be very evident.
Staining.

1. Fluorescein stain. Fluorescein may stain any denuded area of corneal epithelium. The reduced tear lake could easily be appreciated with fluorescein.
2. Rose Bengal Stain. Rose Bengal (solution 1 % or strip) stains the damaged devitalized epithelial cells of the conjunctiva and cornea. It can detect even mild cases of Keratoconjunctivis Sicca (KCS) by staining the palpabral conjunctiva in the form of two triangles with their base towards limbus..
Tear Film Break Up Time. (TBUT)
It is a quantative measurement of tear film stability. A mucous deficiency results in beading of the aqueous tear around the small amount of available mucous on the epithelial surface and reduction of TBUT.
Diagnosis.

Diagnosis is most often based on the complaint of the patient without any evident cause in the eye. Quite often, persistent fishing for ropy mucous discharge is very classical and so is the importance of the complaint of increased discomfort in dry and windy environment.
Diagnostic tests mostly employed are as under
a. Shirmer Test. The test is used to quantitatively measure the tear secretions by the lacrimal gland, and should be done before any other examination as the manipulation of the eyelid and eye can alter the results of the test.
Shirmer I Test. Is used to measure tear secretion rate without anesthesia.
Shirmer II Test is done similar to Shirmer one but after instillation of anesthetic drops.
Other employed tests are :
a. Tear Function Index (TFI)
b. Fluophotometery.
c. Tear Osmolarity.
Treatment

Conservative
1. Patient Information. Patient must be educated and fully informed about the disease as well as he must be explained the limitations of medical management. This maintains the patient’s confidence in your line of treatment.
2. Controlling the surroundings. Special stress must be put to control the surroundings to minimize the severity of the condition.
a. Still Air. Patient must avoid sitting facing direct flow of air from air conditioners, ventilators, windows or fans. It is better that patient avoid sitting in front of door in a room. While driving car, the car window must be closed and the patient should use glasses. Car A.C. wind should not blow directly on the face.
b. Humid Air. Even if there is no refractive error, patient must wear glasses. Just by wearing spectacles, the humidity between the eyes and the spectacles rises by 2 %. Spectacles with side panels and moist chamber may be reserved for more severe cases. Humidifiers must be used in the rooms. There are air-conditioners available with attached humidifiers.
Special glasses with moist inserts ameliorate severe dry eye symptoms. The moist inserts on the side panels increase the ambient humidity, resulting in a decrease in the tear evaporation from the ocular surface. Another type of moist chamber is obtained more easily and less expensively by using swimming goggles. The most favorable range of relative humidity for minimizing tear evaporation is reported to be 40% to 50 %. Wet gauze mask is an alternative treatment modality.
c. Pure Air. Polluted air is very harmful for dry eye patients. Palpabral aperture must remain open as little as possible. Closed window in the car, helmet with a shield while driving scooter and covering your eyes with goggles while driving bicycle gives some relief. While reading books, the book should be kept as close to chest as possible so as to have minimum palpabral aperture. While looking down, ocular surface exposed to the air is just 1 square centimeter, whereas while looking straight, 2.0 sq. cm. and while looking up, 3,0 sq. cm.
Computer Vision Syndrome. While looking at the monitor, the eyes have the tendency to stare at the screen thereby reducing the blink to about 6-7 blinks a minute. If the computer is at a higher level than the eye, there is further increased evaporation of tears. To avoid computer vision syndrome, one must keep the computer at the lower level than the eyes and a habit must be formed to blink about 10-12 times per minute. When working for long period, one must close the eyes for some time or use some artificial teardrops.

Medical Management

Tear Substitutes.

Tear substitutes are the mainstay in the medical management of dry eye. Variety of tear substitutes is available. Hypotonic non-viscous solutions counteract the hyper tonicity in dry eye syndrome and can last up to two hours. Viscous solution contains cellulose as their base and thus last longer. Preservatives are added to increase the shelf life and the stability of the solution. The commonly used preservatives include benzalkonium chloride, thimerosal, and chlorhexidine. In spite of their low concentration, they can produce toxic effect on the cornea and conjunctiva and adversely affect the dry eye condition.

THE use of unpreserved collyria, and more recently preservatives that are transient or which rapidly oxidize to non-toxic compounds upon exposure to air and the ocular surface, has become routine for those patients requiring more than three or four lubricant drops per day. The tear supplements have focused on maintaining a hypotonic collyrium with normalization of electrolyte concentration to combat the damaging effects of hyper tonicity.

In India, preservative free tear substitutes used are :

Refresh Tear Drops (Allergan),
Gen Teal drops (Novartis) ,
Eye Mist Drops (Avesta) ,
Tear Drops (Milmet)
Celluvisc 1 % (Allergan)
Refresh Liquigel (Allergan)
Tear substitutes are instilled in the eyes 3- 6 times a day
depending on the severity of the condition. If necessary, Refresh
Liquigel or Celluvisc is instilled at bedtime.
Androgens

Role of androgen as a therapy is yet not well established though it is known that in females, lack of Androgens play important role in its etiology.
Topically, androgenic supplementation of artificial tears, appears to lower the Osmolarity of patient’s tears either by retarding evaporation or possibly stimulating tear secretion.

Tear Stimulants
Tear stimulants have as yet not proved very useful.
Recent trials with purinergic P2Y2 agonist has reached phase three trial in USA. The medication designated diquafosol tetrasodium (Inspire Pharmaceuticals, USA) has been extremely well tolerated and increases tear film volume and mucin content. The pharmacological action is to increase fluid transport across the conjunctiva and stimulate mucin release from goblet cells.

Cyclosporine A

Looking to the immunological aspect of the disease, cyclosporin A in the form of topical drops (0.005 %) is being used in moderate to severe form of DES to treat inflammation of the ocular surface and lacrimal gland. The drops are instilled twice a day and the beneficial results are observed within four to six months. The drug may have to be used for whole life. Cyclomune is an immunomodulator. It selectively suppresses lymphocytic functions involved in a disease without actually suppressing the entire immune system. It inhibits T helper cells that are known to cause inflammation of the ocular surface and lacrimal glands in patients with dry eye. The main indication for the use of Cyclomune is surface staining of the cornea. Instillation of drops is associated with stinging sensations, which gradually decrease.
Cyclosporine drops are marketed by Allergan as Restasis in USA and by Avesta in India as Cyclomune

Meibomitis.
A recent study in USA has shown that about 38 % patients with dry eye has concurrent Meibomian gland involvement. Hot wet compresses, betadain scrub, eyelid massage and oral tetracycline or doxycycline, may treat Meibomian inflammation.

Topical Steroids (Soft steroids)

Topical steroids are being tried in some of the resistant or advanced cases of dry eye or in patients who have severe itching. Lodeprednol etabonate 0.2 % is a good choice for long-term use. It is soft steroid that is activated by enzymes as it passes through the cornea. It seems to have very little effect on IOP. It is marketed as Alrex by Bausch & Lomb
Mucolytics.
Topical 5 percent Acetylcysteine drops are recommended for instillation four times a day. It is effective in eyes with excessive mucous.
Future Therapies.
Apart from tear substitutes, anti-inflammatory therapy, androgen hormone replacement, and tear stimulant diquafosol tetrasodium may form main therapeutic measures. Herbal supplements such as oil of primrose and flax seed oil are reported to be help in relieving symptoms of dry eye and Meibomitis. Essential fatty acids of omega 3 and specially omega 6 category as food supplements are showing some promising results.
Surgical Management

A. Canalicular Obstruction by Punctal Plugs
It is a simple procedure that decreases the tear drainage markedly and improves the qualitative and quantitative component of tears. A decrease in osmolarity of the tears is noted. Improvement can be seen by Schirmer and TBUT test.
B. Punctal Patch Technique This is most efficacious surgical technique for long lasting occlusion of the lacrimal drainage system. In this technique a raw area is created surrounding upper and lower puncta. A piece of bulbar conjunctiva is taken and transplanted to the punctal wound with its raw surface in contact with the lid and sutured to it with four 9. 0 stitches.
Summary

Dry eye disease appears to be on increase due to multiple factors. Inspite of great advance in understanding and diagnosing the disease, the disease remains a challenge to medical profession. Preservative free drops have significantly improved the quality of life of dry eye patients. Anti-inflammatory therapy, androgen hormones and tear stimulant, namely, diquafosol tetrasodium and probably some herbal drugs hold great hope for a DES patient.