DRY EYE=20 SYNDROME: EMERGING CHALLENGE IN OPHTHALMOLOGY

DR. M.=20 R. JAIN M.S, FICS, FAMS

MEDICAL=20 DIRECTOR

M. R. J=20 INSTITUTE AND JAIN EYE HOSPITAL, JAIPUR

Dry Eye=20 Syndrome is the most frequent disorder in Ophthalmology. Fortunately, = only=20 infrequently it becomes = most=20 severe. Although the condition was recognized as a clinical disorder in = the year=20 1920 and described clinically in the early 1930=92s, the greatest amount = of=20 information both from an epidemiological and pathogenetic perspective = has=20 accrued during the last ten years.

What is=20 Dry Eye Syndrome.

Dry Eye=20 Syndrome is a disorder of the preocular tearfilm that results in damage = to the=20 ocular surface and is associated with symptoms of ocular discomfort. Dry = eye is=20 characterized by instability of the tearfilm that can be due to = insufficient=20 amount of tear production or due to poor quality of tearfilm, which = results in=20 increased evaporation of the tears.

Dry eye=20 therefore can mainly be divided in two groups, = namely

Aqueous=20 production deficient=20
Evaporative=20

Prevalence=20 of dry eye.

No=20 authentic prevalence survey has been conducted in India but it is noted = that out=20 of the patients above the age of 30 years attending the outdoor, one out = of=20 every five has a complaint pertaining to dry eye. A recent survey = conducted in=20 year 2002, based upon a well =96 characterized population of adult men = and women=20 in the USA, identified a prevalence of 6.7 percent in women over the age = of 50=20 and 2.3 % in men over the age of 55.These rates extrapolate to = potentially 9.1=20 million dry eye patients in USA alone.

In=20 women at the age of 50-52 when menopause usually sets in, an imbalance = occurs=20 between the oestrogen and androgen hormone due to decrease of androgens = after=20 the menopause. Decrease in androgen levels, excites inflammation in = lacrimal=20 gland and ocular surface, disrupting the normal homeostatic maintenance = of the=20 lacrimal gland and ocular surface.

The=20 factors which has increased the incidence of dry eye can be narrated as=20 under

a.=20 increasing longitivity of the population

b.increased=20 consumption of medication, both systemically and topically which have = adverse=20 effect on the production of high quality of tears

c.=20 increased computer use

d.=20 increased contact lens use and cosmetic surgery of LASIK/=20 LASEK

e=20 better understanding and diagnosis of dry eye.

f=20 possibly, adulteration in the food?

TEAR=20 FLUID COMPOSITION

The=20 tear is found to be composed of three fractions: albumin, globulin and = lysozyme.=20 The immunoglobulins found in normal tear fluid are lgA, lgG and IgE. lgA = predominates in the secretory form. IgE levels increase in patients with = allergic conjunctivitis and lgM is found in tears of patients with acute = infections. Lysozyme may act synergistically with lgA in causing lysis = of=20 bacteria. Tears also contain lactoferrin, which has some antibacterial=20 effect.

TEARS:=20 VITAL STATISTICS:

Average=20 glucose concentration of the tears is 2.5 mg/dl.=20
Average=20 tear urea level is 0.04 mg/dl.=20
Electrolytes=20 such as K, Na and Cl occur in higher concentration in the tears than = in the=20 blood.=20
Average=20 pH of the tears is 7.25.=20
Osmolality=20 is 309 mosm/ liter (hypertonic in patients with the dry eye=20 syndrome).=20
Surface=20 tension of the tear film is 40-42 mN/m.=20
Refractive=20 index of the tear film is 1.336.

Under=20 normal conditions, the tear fluid forms a thin layer over the cornea and = conjunctiva, this is known as the pre ocular tear film. The pre ocular = tear film=20 measures 8 um thick and covers the corneal and conjunctival epithelial=20 surface.

The=20 pre-ocular tear film acts as an important component of the ocular = defense=20 mechanism.

It=20 makes the cornea a smooth optical surface.=20
It=20 helps to wet the cornea and the conjunctiva and prevents them from=20 drying.=20
It=20 flushes out the debris and organisms from the corneal=20 surface.=20
It=20 has bactericidal properties due to the presence of lysozyme, = lactoferrin and=20 betalysin.

Immunoglobulins=20 (lgA) and specific antibodies in the tears defend the eye against = external=20 infections.=20
Frictional=20 trauma between the tarsal and the bulbar conjunctiva and cornea is = minimized=20 by the lubricating action of the tear film.=20
It=20 enables the anti-inflammatory cells to reach the injured areas of the = cornea=20 and the conjunctiva.=20
It=20 provides the epithelial cells with glucose, oxygen and growth=20 factors.

Distribution=20 System:

The=20 distribution system for the tear film consists of the eyelids and the = tear=20 meniscus along the lid in the open eye. Each blink compresses the = superficial=20 lipid layer. The mucous layer acts as a scavenger to pick up any lipid=20 containing debris and carry it to the fornices. As the eyelid reopens, a = new=20 tear- film layer is spread across the ocular surface. Inadequacy of any = layer of=20 the tear film increases its instability and may accelerate tear breakup = time=20 (BUT).

The=20 distribution system of the lids also acts as a pumping mechanism to draw = tears=20 into the excretory system.

EXCRETORY=20 SYSTEM:

Blinking=20 is an important factor in tear distribution and also plays a pivotal = role in=20 tear drainage. Crucial to proper lacrimal excretory function is the = punctum, the=20 entry point for lacrimal drainage. Proper tear elimination requires that = the=20 punctum be apposed to the globe.

Spontaneous=20 blinking replenished the fluid film by pushing a thin layer of fluid = ahead of=20 the lid margins as they come together. The excess fluid is directed into = the=20 lacrimal lake- a small triangular area lying in the angle bound by the = innermost=20 canalculi via the nasolacrimal duct, and then drained over the = nasopharynx and=20 oropharynx to be swallowed.

The=20 drainage pathway may account for up to 90% of the fate of tears. The = remainder=20 evaporates. Thus, the act of blinking exerts a suction-free force action = in=20 removing tears the lacrimal lake and emptying them into the nasal=20 cavity.

Functions=20 of Preocular Film

Tear=20 Film

It=20 comprises of three layers

Outer=20 Lipid layer

It is=20 formed by the oily secretion of Meibomian glands. It acts as a lubricant = and=20 prevents evaporation of tears.

Middle=20 Aqueous Layer

It is=20 the main tear fluid liberated from lacrimal gland and Accessory glands. = It=20 contains proteins, immunoglobulins, lysozyme, lactoferrin and betalysin. = It=20 provides moisture to the eye, nutrition to the cornea and antibacterial=20 activity. It provides the epithelial cells with glucose, oxygen and = growth=20 factors. It flushes out the debris and organisms from the corneal = surface and=20 drains into nasolacrimal canal.

Inner=20 Mucous Layer

The=20 innermost mucous layer of the tear film forms a highly hydrophilic = wetting=20 surface over the hydrophobic epithelial surface of the cornea and = conjunctiva.=20 The mucous also reduces the surface tension between the lipid layer of = the tear=20 film and the water layer, thus contributing to the stability of the tear = film.

Pathogenesis=20 of Dry Eye

It is=20 an established fact that any lacrimal gland damage would result in = decreased=20 tear flow. This leads to decreased washout of the tear surface debris = and=20 bacterias as well as increased presence of inflammatory cytokines and = decreased=20 growth factors to maintain ocular surface = integrity.

Almost=20 all tear flow is due to a reflex mechanism due to stimuli from cornea = sending=20 impulses to the brain and to the lacrimal gland. Any thing which = disturbs=20 corneal sensations like hormonal imbalance, contact lenses, LASIK = surgery or any=20 other trauma to the eye, may it be surgical or = accidental.

Infection=20 of the lacrimal gland may it be primary (dacryoadenitis) or = immunological due to=20 rheumatism of joints or prolonged conjunctivitis may result in decreased = formation of aqueous. As a result of inflammation, activation of matrix=20 metalloproteinase enzymes (MMP-9) was identified which has further = potential to=20 damage the ocular surface. It is now generally recognized that = inflammation is=20 an integral part of the pathogenesis of dry eye disease and a target for = dry eye=20 therapy.

The=20 normal interaction of the tear film and ocular surface is conditioned by = a=20 background of androgenic hormonal support that prevents inflammation and = an=20 intact corneal sensation that stimulates secretion by the lacrimal gland = to=20 produce tears that nourish and protect the ocular surface. When there is = perturbation of the normal homeostatic controls, dry eye occurs either = as an=20 aqueous tear deficiency or excess evaporative loss with subsequent = damage to the=20 ocular surface. This disease state creates a vicious spiral of = increasing=20 inflammation of the lacrimal gland and ocular surface that further = suppresses=20 normal corneal sensation and leads not only to suppression of tear = secretion but=20 to further damage to the ocular surface.

The=20 aqueous deficient dry eye (keratoconjunctivitis sicca) is a disturbance = of the=20 neuro-humoral interaction of the ocular surface which interrupt = secretomotor=20 nerve impulses to the lacrimal gland that results in inflammatory = suppression of=20 aqueous secretion, a necessary component of the tearfilm, with = subsequent damage=20 to the ocular surface, producing symptoms of ocular irritation and = discomfort.=20 The evaporative dry eye is a disturbance of the stability of the = tearfilm, which=20 is usually due to abnormalities of Meibomian gland secretion or abnormal = eyelid=20 position and movement. Both types of dry eye results in damage to the = ocular=20 surface and symptoms of ocular discomfort and impaired visual=20 function.

Classification=20 Based On Etiology

Murube=20 (1996) has subdivided dry eye in following 10 families. These=20 are:

Age=20 Related. Lacrimal secretion begins to decrease after the age of 30 = years. At=20 the age of 6o, we reach the borderline between the production and = need. At the=20 age of 90, almost all persons have dry eye.=20
Hormonal.=20 At the age of menopause almost every women develops dry eye either = mild or=20 moderate. Recent research has shown that it is due to lowering of = androgen=20 levels produced by the ovaries. Men develop dry eye related to = hormones with=20 less frequency and intensity than women.=20
Pharmacological.=20 There is adverse effect on production of tears due to preservatives in = teardrops used for long period. Glaucoma patients are more prone to = this=20 problem due to prolonged therapy.

Systemic=20 drugs like antidepressants, antihypertensives, antihistaminics,=20 anticholinergics, antipsychotics, angiolytics, antiparkinsonians, = diuretics and=20 hormones too can cause dry eye.

Immunological:=20 This is related to autoimmune reaction in exocrine glands affecting = outside=20 body secretion like secretion of tears, saliva, sweat and vaginal = secretions.=20 The Sjogren=92s syndromes are those in which patient=92s immunological = system=20 attacks its own exocrine glands. Rheumatism, cicatricial pemphigoid = and=20 erythema multiform can lead to Sjogren=92s syndrome. =
Infection.=20 Chronic infection of conjunctiva can affect mucous secretion leading = to mucin=20 deficiency and infection of lacrimal glands can affect aqueous = secretion.=20 Inflammation of lids may affect oily secretion. Any of the component = if=20 affected, tearfilm is disturbed.=20
Hypo=20 nutrition. Avitaminosis A, and alcoholism that leads to poor = intestinal=20 absorption may give rise to dry eye.=20
Traumatic:=20 Any trauma to the eye may it be accidental or surgical, can = precipitate dry=20 eye. Major surgeries like removal of tumour etc has more chances to = cause dry=20 eye. Cataract or glaucoma surgery too can be responsible especially in = older=20 persons.=20
Neurological.=20
1. Post=20 LASIK. Lasik leads to = the=20 development of temporary dry eye in about 4 percent of patients. = Wilson=20 (2001) observed rose- Bengal staining and punctate erosions without=20 pre-existing dry eye and labeled it as neurotrophic epitheliopathy. = He=20 believes that this change in epithelium is attributed to transection = of a=20 significant number of the afferent sensory nerves in the cornea = during=20 formation of the flap and, therefore, interruption of the = cornea-trigeminal=20 nerve-brainstem-facial nerve-lacrimal gland reflex arc that = influence both=20 basal and stimulated tear production. The Lasik induced dry eye = tends to=20 resolve approximately within 6 months. =

Contact=20 lens wear. Contact lenses when worn for prolonged period, affect = corneal=20 sensations and hence decrease tear secretion. =

Hard=20 and semi soft lenses cause marked corneal anesthesia. Moreover, soft = lenses=20 absorb tears and cause hypertonic tears, which further affects, the = corneal=20 epithelium. Semi soft lenses also affects lipid layer of the tear=20 film.

Defective=20 glands. Responsible for aqueous, mucin and lipid = secretions.=20
Inability to utilize tears. = There is=20 normal production of tears but cornea is unable to use them due=20 to:=20
1. Epitheliopathy=20 or corneal dystrophy, which decreases corneal, wet=20 ability.=20
2. Due=20 to lipid defect the lids are unable to circulate the tears over the = entire=20 ocular surface (lid paralysis, ectropion, = lagophthalmos)=20

B. Classification Based on = the=20 Pathophysiology of Tear Film

Aqueous=20 tear deficiency( ATD)=20
1. Senile=20 or idiopathic atrophy of lacrimal gland=20
2. Menopause=20
3. Hypofunction=20 of lacrimal gland associated with autoimmune diseases like = Sjogren=92s=20 Syndrome

2 Lacrimal Surfactant( = Mucin )=20 deficiency

a. =20 Trauma=20 to conjunctiva

b. =20 Vitamin=20 A deficiency

c. =20 Conjunctival=20 infections : trachoma, diphtheria

d. =20 Pempigoid,=20 erythema, Stevens Johnson=92s Syndrome

e. =20 Chemical,=20 thermal, radiation injury

f. =20 Drug=20 induced : sulpha, epinephrine

3.Lipid=20 Layer Abnormality :

a. =20 Chronic=20 Blepharitis

b. =20 Acne=20 rosaecea

4=20 Impaired Lid Function or Blinking

Neuropralytic=20 lesions of Trigeminal, Facial, Greater Superficial Petrosal Nerve=20 etc.

5=20 Epitheliopathy

Disease of corneal=20 epithelium

6.=20 Other Causes

Drugs=20
VDTS=20 : Visual Display Terminal Syndrome, Computer vision = syndrome=20
Contact=20 Lenses

Symptoms

Dry eye=20 patient can present any one of them or multiple = symptoms:

Itching,=20 burning, irritation, pain, discomfort. There may be pain and photophobia = and=20 blurred vision that improves with blinking. There is usually stringy = ropy mucous=20 discharge, which can increase in the afternoon. The discomfort in the = eye=20 usually increases while reading, watching T.V, air-conditioning system = (lower=20 levels of humidity) or working on the computer. At times there may be = excess of=20 watering, specially during breeze.

All=20 these symptoms are exaggerated during dry and windy=20 conditions.

Some of=20 the patients give a typical history of desire to frequently sprinkle = water into=20 the eyes.

Signs

Tear=20 Lake. Normally at the = lower lid=20 margin there is there is concave tear meniscus of 0.3 to 0.5 mm, which = is called=20 Tear Lake. In dry eye it = is usually=20 less than 0.1mm.

Debris.=20 There is increased debris in the decreased tear lake. Mucous threads = (strings of=20 mucoid discharge) may be seen.

Other=20 Signs. Redundant conjunctiva, injection of the conjunctival vessels, and = sometimes mild chemosis may be present. In the fornix of the = conjunctiva, the=20 threads form owing to a slow tear flow and partly because of the = increased=20 number of the desquamated epithelial cells. In advanced cases, the = conjunctival=20 and corneal dryness may be very evident and may be associated with = chronic=20 blepharitis and blepharospasm.

Staining.

Fluorescein=20 stain. Fluorescein may stain any denuded area of corneal epithelium. = Staining=20 is graded as 0,1,2and 3. 0=3D no corneal stain, 1=3D1/3 of corneal = epithelium=20 stained, 2=3D =BD of corneal area and 3=3Dsevere staining of =BD of = corneal=20 epithelium. The reduced tear lake could easily be appreciated with=20 fluorescein.=20
Rose Bengal Stain. Rose = Bengal=20 (solution 1 % or strip) stains the damaged devitalized epithelial = cells of the=20 conjunctiva and cornea. It can detect even mild cases of = Keratoconjunctivis=20 Sicca (KCS) by staining the palpabral conjunctiva in the form of two = triangles=20 with their base towards limbus. Rose Bengal gives stinging sensations = but=20 anesthetic drug should not be used as it may give false = results. Alcian=20 Blue has similar properties as Rose Bengal but is not usually=20 available.

Tear=20 Film Break Up Time. (TBUT)

=20 It is a quantative measurement of tear film stability. A mucous=20 deficiency results in beading of the aqueous tear around the small = amount of=20 available mucous on the epithelial surface and reduction of TBUT. The = test is=20 performed by asking the patient not to blink for 10 seconds after = instillation=20 of fluorescein. Appearance of a dark spot (dry area) before 10 seconds = is=20 abnormal. Mild to moderate dry eye patients shall usually have TBUT of = 2-3=20 seconds.

Diagnosis.

Diagnosis=20 is most often based on the complaint of the patient without any evident = cause in=20 the eye. Quite often, persistent fishing for ropy mucous discharge is = very=20 classical and so is the importance of the complaint of increased = discomfort in=20 dry and windy environment.

Diagnostic=20 tests mostly employed are as under

Shirmer=20 Test. The=20 test is used to quantitatively measure the tear secretions by the = lacrimal=20 gland, and should be done before any other examination as the = manipulation of=20 the eyelid and eye can alter the results of the = test.=20

Shirmer=20 I Test. Is used to measure tear secretion rate without=20 anesthesia.

Shirmer=20 II Test is done similar to Shirmer one but after instillation of = anesthetic=20 drops.

After=20 instillation of anesthetic drops, the amount of tear secretion is = closure to the=20 basal secretion rate as there should be no stimulus from the filter = paper strip=20 placed in the inferior conjunctival sac. A value of less than 5.0 mm is=20 considered abnormal. The test is quite often not=20 conclusive.

Tear=20 Function Index (TFI) = test. It is=20 a more specific and sensitive test to quantitatively measure the = tears. It=20 takes into account the influence of tear drainage in the measurement = of tears=20 with Shirmer Test. Its numerical value is obtained by dividing the = Shirmer II=20 test value in millimeters by tear clearance rate. The higher the = numerical=20 value of TFI, the better the ocular surface. Values below 96 suggest = dry=20 eyes.=20
Fluophotometery.=20 It is another way to measure tear secretions. It uses decay of sodium=20 fluorescein to measure the tear flow and the tear volume. This test is = costly=20 and not very informative.=20
Tear=20 Osmolarity. It provides qualitative assessment of tear formation. The=20 reference value is 312 mosm/L. This value increases with the severity = of the=20 dry eye.=20
Impression=20 cytology, conjunctival and lateral salivary gland biopsy may be used = to=20 diagnose the etiology of the disease process.In dry eye states there = is marked=20 decrease in goblet cell count.

Classification=20 of Dry Eye Syndrome :

Mild=20 Dry Eye Syndrome : can be = defined=20 in patients who have a Shirmer Test of less than 10 mm in 5 minutes and = less=20 than one quadrant of staining of cornea

Moderate=20 Dry eye Syndrome:

Can be=20 defined as with Schirmer Test reslts of 5-10 mm in 5 minutes with = punctate=20 staining of more than one quadrant of the corneal=20 epithelium.

Severe=20 Dry Eye Syndrome : Can be defined as diffuse punctate or confluent = staining of=20 the corneal epithelium, often ith filaments. Shirmer Test mostly less = than 5 mm=20 in 5 minutes.

=20 Treatment

=20 Conservative

1. =20 Patient=20 Information.=20 Patient must be educated and fully informed about the disease as well as = he must=20 be explained the limitations of medical management. This maintains the = patient=92s=20 confidence in your line of treatment.

2. =20 Controlling=20 the surroundings.=20 Special stress must be put to control the surroundings to minimize the = severity=20 of the condition.

a. =20 Still=20 Air. Patient=20 must avoid sitting facing direct flow of air from air conditioners, = ventilators,=20 windows or fans. It is better that patient avoid sitting in front of = door in a=20 room. While driving car, the car window must be closed and the patient = should=20 use glasses. Car A.C. wind should not blow directly on the=20 face.

b. =20 Humid=20 Air. Even if=20 there is no refractive error, patient must wear glasses. Just by wearing = spectacles, the humidity between the eyes and the spectacles rises by 2 = %.=20 Spectacles with side panels and moist chamber may be reserved for more = severe=20 cases. Humidifiers must be used in the rooms. There are air-conditioners = available with attached humidifiers.

Special=20 glasses with moist inserts ameliorate severe dry eye = symptoms. The=20 moist inserts on the side panels increase the ambient humidity, = resulting in a=20 decrease in the tear evaporation from the ocular surface. Another type = of moist=20 chamber is obtained more easily and less expensively by using swimming = goggles.=20 The most favorable range of relative humidity for minimizing tear = evaporation is=20 reported to be 40% to 50 %. Wet gauze mask is an alternative treatment=20 modality.

c. =20 Pure=20 Air.=20 Polluted air is very harmful for dry eye patients. Palpabral = aperture must=20 remain open as little as possible. Closed window in the car, helmet with = a=20 shield while driving scooter and covering your eyes with goggles while = driving=20 bicycle gives some relief. While reading books, the book should be kept = as close=20 to chest as possible so as to have minimum palpabral aperture. While = looking=20 down, ocular surface exposed to the air is just 1 square centimeter, = whereas=20 while looking straight, 2.0 sq. cm. and while looking up, 3,0 sq.=20 cm.

&n= bsp; =20 Computer Vision Syndrome. While looking at the monitor, = the eyes=20 have the tendency to stare at the screen thereby reducing the blink to = about 6-7=20 blinks a minute. If the computer is at a higher level than the eye, = there is=20 further increased evaporation of tears. To avoid computer vision = syndrome, one=20 must keep the computer at the lower level than the eyes and a habit must = be=20 formed to blink about 10-12 times per minute. When working for long = period, one=20 must close the eyes for some time or use some artificial=20 teardrops.

Medical=20 Management

Tear=20 Substitutes.

Tear=20 substitutes are the mainstay in the medical management of dry eye. = Variety of=20 tear substitutes is available. Hypotonic non-viscous solutions = counteract the=20 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=20 are added to increase the shelf life and the stability of the solution. = The=20 commonly used preservatives include benzalkonium chloride, thimerosal, = and=20 chlorhexidine. In spite of their low concentration, they can produce = toxic=20 effect on the cornea and conjunctiva and adversely affect the dry eye=20 condition.

THE use=20 of unpreserved collyria, and more recently preservatives that are = transient or=20 which rapidly oxidize to non-toxic compounds upon exposure to air and = the ocular=20 surface, has become routine for those patients requiring more than three = or four=20 lubricant drops per day. The tear supplements have focused on = maintaining a=20 hypotonic collyrium with normalization of electrolyte concentration to = combat=20 the damaging effects of hyper tonicity.

In=20 India, such non- reactive tear substitutes are marketed=20 as:

Refresh=20 Tear Drops (Allergan) it contains carboxymethyl cellulose sodium 5 mg = with=20 stabilized Oxychloro Complex 0.05mg. (Purite)

&n= bsp; =20 Gen=20 Teal drops and Gel (Novartis) it contains hydroxypropylmethyl Cellulose 0.3 % with stabilized=20 H2O2.

=20 Eye=20 Mist Drops (Avesta) it contains hydroxypropylmethyl=20

&n= bsp; =20 Cellulose 0.3 % with stabilized Oxychloro Complex 0.005=20 %.

=20 &n= bsp; Tear=20 Drops (Milmet)=20 Contains=20 sodium

=20 &n= bsp; Carboxymethyl=20 Cellulose 5.0 mg with stabilized Oxychloro

&n= bsp; =20 Complex 0.005 %)

&n= bsp; =20 Celluvisc 1 % (Allergan) it contains carboxymethyl = cellulose=20

&n= bsp; =20 1 percent.

&n= bsp; =20 Refresh=20 Liquigel (Allergan) it contains Carboxymethyl=20

&n= bsp; =20 Cellulose Sodium 1 %.

&n= bsp; =20

&n= bsp; =20 Hyvisc 0.1 and 0.18 percent Sodium Hyaluronate is considered =20 more soothing to the conjunctival epithelium.It has Ph of 7.3. = Increses=20 TBUT and aids healing of Superficial keratitis.

&n= bsp; =20 U. V Lube Drops ( = Patented=20 by FDC ) contains = Chloquin=20 Phosphate drops 0.03 percent. Comes as preservative free unims. Said to = provide=20 Photoprotection.

Imported Tear=20 Substitutes

&n= bsp; =20 Refresh PM =20 (Allergan)

&n= bsp; =20 Gel Visco Tear (Ciba)

&n= bsp; =20 Tears Naturale Free (Alcon)

&n= bsp; =20 Bion Tears (Alcon)

&n= bsp; =20 Lagricel Ofteno (Sophia Laboratories) it contains Sodium=20

&n= bsp; &nb= sp; &nbs= p; = ; = &= nbsp; &n= bsp; =20 Hyaluronate.

&n= bsp; =20 Hyalein Mini 0.1 % and Hyalein Mini 0.3 % (Santen=92s=20

&n= bsp; =20 Japan) contain Sodium Hyaluronate.

&n= bsp; =20 Refresh Endura Drops (Allergan). It is lipid emulsion, which = reduce tear=20 evaporation and stabilize the tearfilm, thereby reducing frequency of = tear=20 instillation.

&n= bsp; =20 Tear substitutes are instilled in the eyes 3- 6 times a day=20

&n= bsp; =20 depending on the severity of the condition. If necessary, Refresh =

&n= bsp; =20 Liquigel or Celluvisc is instilled at = bedtime.

Androgens

Role of androgen as a therapy = is yet not=20 well established though it is known that in females, lack of Androgens = play=20 important role in its etiology.

Topically,=20 androgenic supplementation of artificial tears, appears to lower the = Osmolarity=20 of patient=92s tears either by retarding evaporation or possibly = stimulating tear=20 secretion. This gives an indication that adding androgenic hormones to=20 artificial tears might benefit dry eye patients.

Tear=20 Stimulants

The use=20 of oral or sublingual pilocarpine (Salagen, MGI Pharma) has proven = useful in=20 some patients but has been associated with systemic side effects of = sweating and=20 gastrointestinal upset. Cevimeline (Evosac, Daiichi Pharmaceuticals, = Inc) also=20 stimulate tear and salivary secretion and may be better tolerated than=20 pilocarpine.

Systemic=20 use of congeners of bromhexine have been tried in Europe with = unsatisfactory=20 results.

Recent=20 trials with purinergic P2Y2 agonist has reached phase three trial in = USA. The=20 medication designated diquafosol tetrasodium (Inspire Pharmaceuticals, = USA) has=20 been extremely well tolerated and increases tear film volume and mucin = content.=20 The pharmacological action is to increase fluid transport across the = conjunctiva=20 and stimulate mucin release from goblet cells.

Cyclosporine=20 A

Looking=20 to the immunological aspect of the disease, cyclosporin A in the form of = topical=20 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=20 twice a day and the beneficial results are observed within four to six = months.=20 The drug may have to be used for whole life. Cyclomune is an = immunomodulator. It=20 selectively suppresses lymphocytic functions involved in a disease = without=20 actually suppressing the entire immune system. It inhibits T helper = cells that=20 are known to cause inflammation of the ocular surface and lacrimal = glands in=20 patients with dry eye. The main indication for the use of Cyclomune is = surface=20 staining of the cornea. Instillation of drops is associated with = stinging=20 sensations, which gradually decrease.

Cyclosporine=20 drops are marketed by Allergan as Restasis in USA and by Avesta = in India=20 as Cyclomune

Omega 3=20 Fatty Acids (Omecard); given orally said to decrease the dependence on = Tear=20 substitutes. Fish eaters are said to be relatively resistant to dry=20 eye.

Meibomitis.

A recent study in USA has shown = that=20 about 38 % patients with dry eye has concurrent Meibomian gland = involvement.=20 (Mathers M. D. 2000). Hot wet compresses, betadain scrub, eyelid massage = and=20 oral tetracycline or doxycycline, may treat Meibomian=20 inflammation.

Topical Steroids (Soft=20 steroids)

Topical=20 steroids are being tried in some of the resistant or advanced cases of = dry eye=20 or in patients who have severe itching. Lodeprednol etabonate 0.2 % is a = good=20 choice for long-term use. It is soft steroid that is activated by = enzymes as it=20 passes through the cornea. It seems to have very little effect on IOP. = It is=20 marketed as Alrex (0.2 % ) by Bausch & Lomb and as Lotepred = Drops 0.5=20 percent by Sun Pharmaceutical in India.

Lasik=20 Induced Dry Eye

Clinically=20 post Lasik patients may show punctate epithelial erosions and rose = Bengal=20 staining of the flap. (Neurotrophic epitheliopathy). All cases of Lasik = has to=20 be put on liberal use of preservative free tear substitute drops = immediately=20 after the surgery and continued for a period of 4- 6 months. It is noted = that=20 almost all cases recover within six months. Only few patients, who = already had=20 dry eye symptoms before surgery, may require punctual=20 plugs.

Mucolytics.

Topical=20 5 percent Acetylcysteine drops are recommended for instillation four = times a=20 day. It is effective in eyes with excessive = mucous.

Future=20 Therapies.

Apart=20 from tear substitutes, anti-inflammatory therapy, androgen hormone = replacement,=20 and tear stimulant diquafosol tetrasodium may form main therapeutic = measures.=20 Herbal supplements such as oil of primrose and flax seed oil are = reported to be=20 help in relieving symptoms of dry eye and Meibomitis. Essential fatty = acids of=20 omega =963 and specially omega-3 category as food supplements are = showing some=20 promising results.

Surgical=20 Management

Canalicular=20 Obstruction by Punctal Plugs

It is a=20 simple procedure that decreases the tear drainage markedly and improves = the=20 qualitative and quantitative component of tears. A decrease in = osmolarity of the=20 tears is noted. Improvement can be seen by Schirmer and TBUT=20 test.

Several=20 methods of punctal occlusion have been described including dissolvable = collagen=20 stents, cyanoacrylate adhesive, removable silicon or Teflon plugs, or=20 intracanalicular plugs. The most recently approved innovation is Smart = Plug=20 (Medennium Inc) that is a thermolabile polymer that when inserted into = the=20 canaliculus conforms to the diameter of the canaliculus to produce=20 occlusion.

Canalicular=20 block is obtained by inserting a silicon plug in the puncta. There are = two types=20 of plugs:

a. =20 Punctal=20 plug A. In this part of the plug remains visible over the=20 puncta

b. =20 Punctal=20 plug resides completely within the canalicular canal. (Herrick=20 plug)

Almost=20 75 percent of patients tolerate the plugs well. In some of the patients, = we may=20 have to remove the plugs. The insertable variety can be eliminated from = the=20 canaliculus by irrigating the canal with saline.

Canalicular=20 Obstruction by cautry. Puncta can be temporarily blocked by thermal or = diathermy cautry or by Argon Laser. An Argon Laser focused on the = punctal=20 surface causes overheating and destroys the punctum. (results not=20 reliable)=20
Punctal=20 Patch Technique This is most efficacious surgical technique for long = lasting=20 occlusion of the lacrimal drainage system. In this technique a raw = area is=20 created surrounding upper and lower puncta. A piece of bulbar = conjunctiva is=20 taken and transplanted to the punctal wound with its raw surface in = contact=20 with the lid and sutured to it with four 9. 0 = stitches.=20

Summary

Dry eye=20 disease appears to be on increase due to multiple factors. Inspite of = great=20 advance in understanding and diagnosing the disease, the disease remains = a=20 challenge to medical profession. Preservative free drops have = significantly=20 improved the quality of life of dry eye patients. Anti-inflammatory = therapy,=20 androgen hormones and tear stimulant, namely, diquafosol tetrasodium and = probably some herbal drugs hold great hope for a DES=20 patient.

Further=20 Reading

Foulks=20 G.N. Der Eye Part I : Understanding the epidemiology and Pathogenesis.=20 Highlights Of Ophthalmology. Vol.31 (1) 2003, Pg = 21-26

Boyd B=20 F New = Horizons in the=20 relief and control of Dry Eye Vol 29 (5) 2001 Pg 55-65 =

Bairagi=20 D Dry Eye Syndrome. Sight, Mediworld Publication 2004 Pg=20 6-10

Symposium on Changing Paradigms = in the=20 Diagnosis and Treatment Of Dry Eye. World Eye View July 2004.=20 Pg2-11.

Pflugfelder=20 SC: Anti =96 inflammatory therapy of Dry Eye. The Ocular Surface 2003: = 1:=20 31-36

Foulks=20 GN: Dry Eye- Part II: Management and new treatment options. Highlights = Of=20 Ophthalmology. Vo. 31 (2), 2003, pg.1-8

Murube=20 J, Tsubota K: Dry Eye: What is new in understanding its nature and = effective=20 management? Highlights of Ophthalmology Bimonthly Journal Vol 24, No 5, = 1996.=20

Wilson=20 Se: Lasik induced neurotrophic epitheliopathy. Ophthalmology, June=20 2001.

Murube=20 J Advances in Diagnosis and management of the dry eye. Highlights of=20 Ophthalmology 1993: 21: 10: pg.81-88.Dilly P. N: Structure and function = of Tear=20 Film. Adv Exp. Med Biol 1994; 350:239-247.

Kanski=20 J. J. Clinical Ophthalmology ed. 4 Butterworth, = 1999.

Keshner.=20 Ophthalmic Medication and Pharmacology, Slack. Inc. = 1994

Zimmerman,=20 Text Book Of Ocular Pharmacology, Lippincott and William and Wilkins=20 1997

A=20 Comprehensive Review of Dry Eye Syndrome : A monogram br FDEC=20 Ltd

Ocular=20 Surface Disease : Dry Eye. Chapter 2 & 3 By J. M. Castillo and M.=20

Rolando. Published by Novartis = Ophthalmics=20 2004