CHANGE YOUR DESTINY

Prof Dr. M. R. Jain

Most people know that DNA is the ‘blueprint of life’ and is located in every cell of the body. In addition to each chromosome’s 2 strand double helix of DNA, there are an additional 10 etheric strands of DNA available to each human, which have been dormant since the beginning of recorded history.

A human DNA's function is to tell the body how to build proteins. The DNA in humans is broken up into 46 chromosomes - which each carry a few thousand genes.

Proteins are capable of controlling most of what makes us who we are! A gene provides the instructions for one particular protein. There are thousands of genes because thousands of different proteins are needed to make/operate all the functions of a body.

If there is a fault in a gene (due to an error or mutation) - that means that the protein it gives the instructions for will be made incorrectly. This is why gene mutations can cause diseases - these are called genetic diseases

Scientists acknowledge that we currently only use 3% of our current 2 strand DNA. Additional strand possesses attributes that permit the individual to perform greater human accomplishments. Thus, we live in a society where people are sick, unhappy, stressed out, create wars, have difficulty experiencing love, and are totally disconnected with the universe. Most people have to meditate for many years just to have a so-called ‘mystical’ experience, that’s how disconnected we are now. Imagine activating 100% of your 2 strand DNA, PLUS 10 additional strands! You will go from using 10% of your brain to becoming a multi-dimensional being with psychic, telepathic, and manifestation abilities beyond anything you’ve ever dreamed of. Plus, you will stop the aging process and actually start to rejuvenate to look and feel YOUNGER.

Our thoughts, our activities, our dedication, our environment, our diet, the earth and the Yogic exercises with meditation can modify our genes and activate our DNA strands to make us totally a different human beings.

STITCHLESS PHACO CATARACT SURGERY WITH FOLDABLE IOL.

Cataract surgery is now safe in Diabetics and Hypertensive patients

Opacification of crystaline lens is termed as Cataract which usually occurs due to old age but can occur due to trauma, some disease in the eye or due to use of certain drugs like steroids. Use of cortisone drops in the children’s eyes for allergic conjunctivitis can be very dangerous and cause Glaucoma and Cataract.

In modern time , we perform stitchless cataract sugery using Ultrasonic Rays which emulsify the lens. The incision made is just 2.5 mm. The emulsified lens is aspirated by the Ultrasonic P{haco Pencil and a foldable IOL is injected in the eye through the same opening of 2.5 mm. The surgery is practically painless and takes 15-20 minutes.Within 2-4 hours the patch is removed from the eye andpatient can even drive his own car back home.

In modern time, since we emulsify the lens and hence we perform surgery in a immature cataract. The surgery can be safely undertaken when ever a patient is economically blind, i.e, when he is unable to perform his normal duties. In a driver, we undertake surgery very early since he gets even if cataract is only 10 percent.

How safe is cataract surgery?

In modern time, cataract surgery , in expert surgeon is 98 percent safe.

Does the patient need glasses after lens transplant?

Ans. Generally yes. all patients need glasses of minor power after the Phaco Surgery. Near glasses are must.

What are multifocal lenses?

Multifocal lenses are aimed to provide patient normal vision for distance and near without glasses. The multifocal IOL are costly and they hqavea problem of Glare Blindness if you driving car or scooter. TThey are mostly recommended in motivated patients who know their merits and demerits and sit in shaufer driven cars.

Most of the time after Phaco surgery, a patient has practcally no restriction and can resume his duties within 5-10 days or a lady can cook within 4-5 days.No restriction of food.

DRY EYE SYNDROME: EMERGING CHALLENGE IN OPHTHALMOLOGY

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

MEDICAL DIRECTOR

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

Dry Eye Syndrome is the most frequent disorder in Ophthalmology. Fortunately, only infrequently it becomes 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 Syndrome.

Dry Eye Syndrome 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 mainly 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?

TEAR FLUID COMPOSITION

The tear is found to be composed of three fractions: albumin, globulin and lysozyme. 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 bacteria. Tears also contain lactoferrin, which has some antibacterial effect.

TEARS: VITAL STATISTICS:

· Average glucose concentration of the tears is 2.5 mg/dl.

· Average tear urea level is 0.04 mg/dl.

· Electrolytes such as K, Na and Cl occur in higher concentration in the tears than in the blood.

· Average pH of the tears is 7.25.

· Osmolality is 309 mosm/ liter (hypertonic in patients with the dry eye syndrome).

· Surface tension of the tear film is 40-42 mN/m.

· Refractive index of the tear film is 1.336.

Under 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 measures 8 um thick and covers the corneal and conjunctival epithelial surface.

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

1. It makes the cornea a smooth optical surface.

2. It helps to wet the cornea and the conjunctiva and prevents them from drying.

3. It flushes out the debris and organisms from the corneal surface.

4. It has bactericidal properties due to the presence of lysozyme, lactoferrin and betalysin.

5. Immunoglobulins (lgA) and specific antibodies in the tears defend the eye against external infections.

6. Frictional trauma between the tarsal and the bulbar conjunctiva and cornea is minimized by the lubricating action of the tear film.

7. It enables the anti-inflammatory cells to reach the injured areas of the cornea and the conjunctiva.

8. It provides the epithelial cells with glucose, oxygen and growth factors.

Distribution System:

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

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

EXCRETORY SYSTEM:

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

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

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

Functions of Preocular Film

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 prevents evaporation of tears.

Middle Aqueous Layer

It is the main tear fluid liberated from lacrimal gland and Accessory glands. It contains proteins, immunoglobulins, lysozyme, lactoferrin and betalysin. 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.

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.

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

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

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.

Classification Based On Etiology

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

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. Wilson (2001) observed rose- Bengal staining and punctate erosions without pre-existing dry eye and labeled it as neurotrophic epitheliopathy. He believes that this change in epithelium is attributed to transection of a significant number of the afferent sensory nerves in the cornea during formation of the flap and, therefore, interruption of the cornea-trigeminal nerve-brainstem-facial nerve-lacrimal gland reflex arc that influence both basal and stimulated tear production. 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.

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

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)

B. Classification Based on the Pathophysiology of Tear Film

1. Aqueous tear deficiency( ATD)

a. Senile or idiopathic atrophy of lacrimal gland

b. Menopause

c. Hypofunction of lacrimal gland associated with autoimmune diseases like Sjogren's Syndrome

2 Lacrimal Surfactant( Mucin ) deficiency

a. Trauma to conjunctiva

b. Vitamin A deficiency

c. Conjunctival infections : trachoma, diphtheria

d. Pempigoid, erythema, Stevens Johnson's Syndrome

e. Chemical, thermal, radiation injury

f. Drug induced : sulpha, epinephrine

3.Lipid Layer Abnormality :

a. Chronic Blepharitis

b. Acne rosaecea

4 Impaired Lid Function or Blinking

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

5 Epitheliopathy

Disease of corneal epithelium

6. Other Causes

a. Drugs

b. VDTS : Visual Display Terminal Syndrome, Computer vision syndrome

c. Contact Lenses

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, air-conditioning system (lower levels of humidity) 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 (strings of mucoid discharge) may be seen.

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

Staining.

1. Fluorescein stain. Fluorescein may stain any denuded area of corneal epithelium. Staining is graded as 0,1,2and 3. 0= no corneal stain, 1=1/3 of corneal epithelium stained, 2= ½ of corneal area and 3=severe staining of ½ 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. Rose Bengal gives stinging sensations but anesthetic drug should not be used as it may give false results. Alcian Blue has similar properties as Rose Bengal but is not usually available.

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. The test is performed by asking the patient not to blink for 10 seconds after instillation of fluorescein. Appearance of a dark spot (dry area) before 10 seconds is abnormal. Mild to moderate dry eye patients shall usually have TBUT of 2-3 seconds.

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.

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

a. Tear Function Index (TFI) test. It is a more specific and sensitive test to quantitatively measure the tears. It takes into account the influence of tear drainage in the measurement of tears with Shirmer Test. Its numerical value is obtained by dividing the Shirmer II test value in millimeters by tear clearance rate. The higher the numerical value of TFI, the better the ocular surface. Values below 96 suggest dry eyes.

b. Fluophotometery. It is another way to measure tear secretions. It uses decay of sodium fluorescein to measure the tear flow and the tear volume. This test is costly and not very informative.

c. Tear Osmolarity. It provides qualitative assessment of tear formation. The reference value is 312 mosm/L. This value increases with the severity of the dry eye.

d. Impression cytology, conjunctival and lateral salivary gland biopsy may be used to diagnose the etiology of the disease process.In dry eye states there is marked decrease in goblet cell count.

Classification of Dry Eye Syndrome :

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

Moderate Dry eye Syndrome:

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

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

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, such non- reactive tear substitutes are marketed as:

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

Gen Teal drops and Gel (Novartis) it contains hydroxypropylmethyl Cellulose 0.3 % with stabilized H2O2.

Eye Mist Drops (Avesta) it contains hydroxypropylmethyl

Cellulose 0.3 % with stabilized Oxychloro Complex 0.005 %.

Tear Drops (Milmet) Contains sodium

Carboxymethyl Cellulose 5.0 mg with stabilized Oxychloro

Complex 0.005 %)

Celluvisc 1 % (Allergan) it contains carboxymethyl cellulose

1 percent.

Refresh Liquigel (Allergan) it contains Carboxymethyl

Cellulose Sodium 1 %.

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

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

Imported Tear Substitutes

Refresh PM (Allergan)

Gel Visco Tear (Ciba)

Tears Naturale Free (Alcon)

Bion Tears (Alcon)

Lagricel Ofteno (Sophia Laboratories) it contains Sodium

Hyaluronate.

Hyalein Mini 0.1 % and Hyalein Mini 0.3 % (Santen's

Japan) contain Sodium Hyaluronate.

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

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. This gives an indication that adding androgenic hormones to artificial tears might benefit dry eye patients.

Tear Stimulants

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

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

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

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

Meibomitis.

A recent study in USA has shown that about 38 % patients with dry eye has concurrent Meibomian gland involvement. (Mathers M. D. 2000). 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 (0.2 % ) by Bausch & Lomb and as Lotepred Drops 0.5 percent by Sun Pharmaceutical in India.

Lasik Induced Dry Eye

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

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-3 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.

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

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

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

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

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

B. Canalicular Obstruction by cautry. Puncta can be temporarily blocked by thermal or diathermy cautry or by Argon Laser. An Argon Laser focused on the punctal surface causes overheating and destroys the punctum. (results not reliable)

C. 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.

Further Reading

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

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

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

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

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

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

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

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

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

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

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

Rolando. Published by Novartis Ophthalmics 2004

GLAUCOMA: A BLINDING DISEASE OF THE EYES

PROF D. M. R. JAIN M.S, FICS( USA), FACLP( LONDON), FAMS

MEDICAL DIRECTOR

JAIN EYE CLINIC & HOSPITAL

JAIPUR, INDIA

'The disease affects about eight million people in India. In the world, about 6.7 million people are totally blind. Fifty percent of the population in India are unaware about the disease in their

eyes and are in the process of becoming blind.'

Every eye has certain amount of intraocular pressure to maintain its structure and function. This is called as normal intraocular pressure, which ranges between 13 to 21 mm of mercury.

If there is rise of intraocular pressure which is not compatible with normal health and function of the eye, we call it glaucoma. Usually when the pressure exceeds 21 mm of mercury (Hg), we consider that the patient is glaucomatous but in some eyes, patient may suffer glaucomatous damage even at the pressure of 17-18mm of mercury. We term this condition as Normotensive glaucoma. In other words, pressure is a very important parameter to diagnose glaucoma but certain other factors may play a role to cause glaucomatous damage even if the pressure is within normal range.

There are following types of glaucomas:

1 Chronic Simple Glaucoma (Open Angle Glaucoma)

2 Acute Congestive Glaucoma (Angle closure or Narrow Angle Glaucoma)

3. Secondary Glaucomas: These are the glaucomas due to some other disease in the eye like uveitis, cataract, trauma, hemorrhage, tumour etc.

4. Steroid Glaucoma

5. Congenital Glaucoma. Glaucoma occurring in a newborn child.

Chronic Simple Glaucoma.

This is the commonest glaucoma occurring in ..percent of persons. This glaucoma has a very incipient onset with practically no symptoms but has the potentiality to cause gradual and total irreparable blindness.

What Causes Rise Of IOP. Aqueous humour is constantly formed by the ciliary body. This aqueous travels to the anterior chamber, performs its function of nutrition and take away waste products and leaves the eyeball by traveling towards angle of anterior chamber and than through the trabecular spaces and out of the eyeball. This process of constant formation and drainage of aqueous maintains the intraocular pressure within the normal range i.e., 13 to 21mm Hg. In some patients, the trabecular spaces gradually become narrow and hence produces resistance to the outflow, thereby the intraocular pressure gradually rise which may quietly and slowly damage the structure and function of the eye.

Age Of Onset. This glaucoma usually occurs after the age of 35 years but may occur in young age also. With the age, the incidence of the disease increases and hence it becomes a significant aging problem. The incidence varies from country to country but in India, almost 3-4 percent of the population after the age of 40 suffer from this problem and out of this 50 percent of the patients are unaware of it and hence gradually become blind. The incidence in coloured races is more than in white races.

Hereditary. Most often this disease is hereditary and hence children with parents or grand parents having glaucoma, must get them examined at the age of 30 and 35 and thereafter every two years. The incidence is 15 times higher than general population.

The incidence is still higher if a sibling has the disease.

Risk Factors. Main risk factors are raised IOP, hereditary, myopic refractive error, diabetes, hypertension and advanced age. Myopic eyes have about 20 percent more chances of getting glaucoma and diabetes increases the incidence by about 10 percent.

Symptoms. Almost 30 percent of patients have no symptoms till the disease is quite advanced. Some patients may have mild blurring of vision or complain of simply watering in the eyes not responding to conventional drops, ocular discomfort or pain, visual fatigue or headache. Patients having normal distance vision may complain of defective near vision much before the common age of onset of presbyopia i. e., at the age of 35-38 years. Some patients with moderately advanced disease may have delayed dark adaptation or dusk blindness. Since the disease mostly affects the field of vision and hence quite a large number of patients do not visit ophthalmologist since their vision may continue to be almost 6/6 even with moderately advanced disease.

Some patients may complain of photophobia or seeing of coloured haloes.

Signs. Following are the signs of glaucoma

1 Raised IOP.

2Affection of field of vision

3 Pupillary reaction may become sluggish

4 Colour of pupil may become bluish-gray

5 Occasionally epiphora- watering of eyes

Diagnosis.

Diagnosing of glaucoma is not always easy. The doctors have to weigh various factors in labeling a patient as glaucomatous since unnecessary use of antiglaucoma drugs may have some adverse effects in some patients and missing the diagnosis may definitely be very harmful. Hence, it is vital that borderline cases of glaucoma is fully examined and investigated by an expert before confirming the diagnosis. Recording of intraocular pressure alone is not sufficient since patient with IOP of 25 mm may not be glaucomatous but a patient with only 14 mm may be suffering glaucomatous damage. And hence almost 30 percent of patients may require services of an expert glaucomologist who has well equipped clinic.

Diagnosis is mostly based on following:

1.Symptoms and Risk factors. As stated above.

2 Tonometry. Recording of IOP

This is the most important test carried out with the help of instruments like Schiotz Tonometer, Goldmann Applanation Tonometer or Non- Contact Tonometer. Later two techniques are more precise.

3.Fundus Examination or Ophthalmoscopy

With the help of Ophthalmoscope, we examine the Retina and the Optic Disc to evaluate effect of raised intraocular pressure on these structures.

Due to increased pressure, a cup in the central part of Optic disc becomes enlarged and the disc colour becomes pale. This results in affection of the fields. Larger the cup or pallor of the disc, more the irreversible damage to the eye. Recently introduced more sophisticated Scanning Laser Ophthalmoscope can pick-up the changes in the retina and optic disc much earlier.

It is said that by the time coventional ophthalmoscopy appreciate the changes in the disc, lot of damage has already occurred to the field of vision.

3.Perimetry. Process of recording the field is called Perimetry.It is a special test that produces map of the complete field of vision. Very early glaucoma can be picked up by this test, more so when a sophisticated Computerized Automated Perimetry is used.

Goldmann Perimeter is moderately reliable manual perimeter but it takes lot of time and hence the cooperation of the patient is difficult.

Computerized Automated Permeters are far more relable and rapid and their results can be stored in the compuer and compared when repeat procedure is done. In these procedures, lights of varying intensities are flashed automatically by a computer around a bowel shaped area and the patient is asked to press a button when he sees the light. This way a definite record of area of field of vision which is partially or totally affected is obtained.

The procedure is more vital for diagnosis. specially in eyes where is pressure is just on the borderline. Recording of field is also essential to evaluate the result of therapy.

Automated Computerized Perimetry is the latest and very precise method to record the fields. Such a record shall distinctly show as to how much field of vision is totally lost and how much area is partly affected.

4.Gonioscopy. Procedure of examination of Angle of Anterior Chamber is called Gonioscopy and is very helpful to precisely pinpoint the type and cause of glaucoma.

It is done with the help of Goldmann Gonio Contact lens.

In recent years still more advanced and sophisticated tests like Confocal Scanning Laser Tomography, Scanning Laser Polarimetry and Optical Cohrens Tomography have emerged which may pickup glaucomatous damage at a very early stage but these are extremely costly and sparsely available.

Prevention. We cannot prevent glaucoma but what we can prevent is the blindness if we are aware of this disease and the risk factors.

Glauco patient under an expert shall rarely become blind if he religiously follows doctors instruction as regards frequency of therapr and regular checkup.

How is glaucoma treated

Medical therapy is aimed to control the intraocular pressure and worsening of visual fields. Medical therapy only controls the disease but does not cure it and hence medications has to be instilled very regularly at prescribed time. Any carelessness even for a day is harmful to the patient.

Basically there are three types of drugs:

1. Drugs which decreases the formation of aqueous

2. Drugs which increases the outflow of aqueous through the trabecular meshwork or Uveo- scleral channels.

3. Drugs which do both.

In modern times , with the advancement of therapy, the doctors have various options to control IOP by utilizing specific drug in a specific person and use of single or multiple drugs.

The principle of treatment is ' to use least amount of medication that produces the best results with the fewest side effects.'

Evaluating all factors , the doctor prescribes a drug which can effectively reduce the IOP.At times by trial and error, the doctor finds out a single or multiple drugs which can achieves ' target IOP' i.e. an intraocular pressure which is going to be safe for that particular person.

Patient must help the doctor by giving a correct family history

Hg.Hg.

EVOLVING CONCEPTS

 Prof Dr M R Jain, FAMS

Medical Director

M.R.J INSTITUTE & JAIN EYE HOSPITAL

JAIPUR, INDIA

ABSTRACT

As one ophthalmologist had mentioned way back a decade ago: 'advocating antioxidants is like shooting in the dark'. It is no more now. Today the pathophysiology of free radical mediated eye degenerative diseases like age-related macular degeneration and cataract are well established, and so is the definite role of antioxidants, particularly carotenoids. As far as eye is concerned, lutein and zeaxanthin have a vital role to play, and these two carotenoids are a must for the eye to be well protected form developing macular degeneration as well as cataract. In addition, lycopene, another carotenoids has a special place in eye defense since it is the best quencher of singlet oxygen - a reactive oxygen species which causes havoc particularly in the eye.

INTRODUCTION

Free radical chemistry began in 1900s when they were determined as cause for fat spoilage. Importance of free radicals in human diseases pathophysiology was first recognized in 1969 when McCord & Fridovich isolated the first antioxidant enzyme superoxide dismutase.

The controversy as regards the use of antioxidants, particularly carotenoids, in ophthalmic diseases seems to be resolving due to advances made in measuring their levels in foods and tissues. There is consistent experimental and epidemiological evidence to substantiate the role of particularly lutein and zeaxanthin in prevention and, to a certain extent, cure of early age-related macular degeneration (ARMD) and cataract formation. Also clinical observations depending upon the recommended dietary modification and therapeutic supplementation presently are encouraging.

FREE RADICALS

DEFINITION

A free radical is defined as any species capable of independent existence and contains one or more unpaired electrons.

HOW FREE RADICALS ARE FORMED?

The various tissues in the human body are formed by innumerable molecules. Each molecule consists of two or more atoms joined together by chemical bonds. An atom, the smallest particle of an element, consists of a core which contains positively charged protons (or positrons) as well as neutral neutrons. In the orbit of each atom (referred to as orbital) are present the electrons (or negatrons). Each orbital can accommodate a maximum of two electrons both of which spin in opposite directions.

Most molecules are non-radical since they contain a paired set of electrons. But oxygen is always electronegative. As a consequence, it pulls electrons away from other atoms (including oxygen itself) and renders these as free radicals.

Oxygen-derived free radicals have a lifespan of only a few microseconds. Their concentration at any single site is miniscule. However the danger lies in their ability to combine with another nonradical to render the latter as free radical. Normally, bonds don't split in a way that leaves a molecule with an odd, unpaired electron. But when weak bonds split, free radicals are formed. Free radicals are very unstable and react quickly with other compounds, trying to capture the needed electron to gain stability.

Fig: Serial formation of free radicals.

Generally, free radicals attack the nearest stable molecule, thereby “stealing” its electron. When the “attacked” molecule loses its electron, it becomes a free radical itself.  This leads to a process of chain reaction. Once such a process has started, it can cascade, finally resulting in the disruption of a living cell.

Radicals can react with other molecules in a number of ways. If two radicals meet, they can combine their unpaired electrons symbolized by.) and join to form a covalent bond (a shared pair of electrons). The hydrogen atom, with one unpaired electron, is a radical and two atoms of hydrogen easily combine to form the diatomic hydrogen molecule:

H. + H. 

Radicals react with nonradicals in several ways. A radical may donate its unpaired electron to a non-radical (a reducing radical) or it might take an electron from another molecule in order to form a pair (an oxidizing radical). A radical may also join onto a nonradical. Whichever of these three types of reaction occurs, the nonradical species becomes a radical. A feature of the reactions of free radicals with nonradicals is that they tend to proceed as chain reactions, where one radical begets another.

SOURCES OF FREE RADICALS

Some free radicals arise normally during metabolism. Sometimes the body's cells or its immune system purposefully create them to neutralize viruses and bacteria. However, environmental factors such as pollution, radiation, cigarette smoke and herbicides can also generate free radicals. Free radicals causing structural damage (to proteins) resulting in aging changes such as cataract and ARMD.

An adult utilizes 3.5 ml oxygen per kg body weight per minute. Assuming a body weight of 70 kgs, this works out to 352.8 liters per day. Even if 1% of oxygen is converted to free radicals, this amounts to 1.72 kg of free oxygen radicals per year!

EXAMPLES SOURCES OF FREE RADICALS

Some free radicals well studied free radicals are:

¨       SUPEROXIDE ANION (O₂^.)

¨       HYDROXYL RADICAL (OH^.)

It is important to note that free radicals such as hydroxyl radical differ from hydroxyl ions in their content of electrons.

REACTIVE OXYGEN SPECIES

These are partially reduced oxygen species which do not contain any unpaired electron. Examples of reactive oxygen species are:

¨       HYDROGEN PEROXIDE (H₂O₂)

¨       HYDROPEROXY RADICAL (HOO^-)

¨       HYPOCHLOROUS ACID RADICAL (HOCl)

Under certain conditions reactive oxygen species have potential to enter free radical reactions to form the more toxic free radicals. Another reactive oxygen species, which is not a free radical, is singlet oxygen (O). In this, a rearrangement of electrons has occurred which allows it to react faster with biological molecules - as compared to 'normal' oxygen.

ANTIOXIDANTS

DEFINITION

Antioxidants can be defined as substances whose presence in relatively low concentrations significantly inhibits the rate of oxidation of the targets.

HOW ANTIOXIDANTS WORK?

Antioxidants serve as natural protectors in the body, mopping up free radicals and reactive oxygen species, which are potentially damaging. Antioxidants protect the tissues in 4 ways:

¨       Physically separating the free radicals / reactive oxygen species from the susceptible molecules of the human body.

¨       Providing molecules which effectively compete for oxygen.

¨       Rapidly repair the damage caused by free radicals / reactive oxygen species.

¨       Lyse the free radicals / reactive oxygen species and rapidly remove these.

CLASSIFICATION OF ANTIOXIDANTS

î      ANTIOXIDANT ENZYMES

¨       Superoxide dismutase

¨       Catalase

¨       Glutathione peroxidase

î      PREVENTIVE ANTIOXIDANTS

¨       Ceruloplasmin

¨       Transferrin

¨       Albumin

î      CHAIN-BREAKING ANTIOXIDANTS

r        Water-soluble*

¨       Uric acid (200-400 mmol/L)

¨       Ascorbate (25-100 mmol/L)

¨       Thiols (400-500 mmol/L)

¨       Bilirubin (10-20 mmol/L)

¨       Flavanoids

r        Fat-soluble*

¨       Tocopherols (20-30 mmol/L)

¨       Ubiquinol-10 (<2 mmol/L)

¨       Beta-carotene (1-2 mmol/L)

¨       Estrogens

The most important antioxidants are three vitamins and three minerals.

r        ANTIOXIDANT VITAMINS

¨       CAROTENOIDS

¨       VITAMIN E

¨       VITAMIN C

r        ANTIOXIDANT MINERALS

¨       SELENIUM

¨       ZINC

¨       MANGANESE

¨       COPPER

carotenoids

Carotenoids circulate in lipoproteins; 53% of beta carotene occurs in low density lipoproteins. Besides the well known beta carotene, the other carotenoids of human importance are:

¨       Lutein

¨       Zeaxanthin

¨       Lycopene

¨       Alpha carotene

¨       Beta cryptoxanthin

As far as the eye is concerned, Lutein and zeaxanthin are exclusively concentrated in the macula, lens and iris. The retina and choroids additionally contain lycopene, alpha- and beta carotene. In the ciliary body, all the carotenoids taken in foodstuff or as dietary supplement get accumulated.

VITAMIN E

Being a fat soluble vitamin, alpha tocopherol is abundant in all cell membranes as well as in lipoproteins. In the eye, vitamin E is present in retina and choroids, and balance in iris and ciliary body. It is important in protection of rods and cones in retina, and also for preventing free radical damage to lens. Vitamin E acts synergistically with vitamin C, beta carotene and selenium for better functioning of glutathione.

VITAMIN C

Vitamin C is protective for the cytoplasm & is also most important for plasma defense. It also occurs in certain cells like muscle, adrenals and eye. Vitamin C has the capacity to regenerate vitamin E. It is more significant in combating free radicals formed due to pollution and cigarette smoke. Vitamin C especially concentrates in ocular tissues and is the first antioxidant to tackle free radicals.

ZINC, MANGANESE & COPPER

Zinc (Zn), manganese (Mn) and copper (Cu) are constituents of superoxide dismutase (SOD) antioxidant enzyme. SOD is widely distributed in tissues as well as fluid compartments. CuZnSOD is present in cytoplasm and nucleus, MnSOD in operates mitochondria whilst CuSOD is most distributed in plasma. SOD attacks free radicals like hydroxyl radical to convert these into hydrogen peroxide.

Besides, Zn serves an important structural role, whilst Cu is necessary for functioning of another antioxidant enzyme called as catalases. Hydrogen peroxide is converted by catalases into harmless water and molecular oxygen.

In the retina, SOD plays an important role by scavenging free radicals to prevent the oxidative damage which plays a role in the development of drusen, an early sign of ARMD. Catalases, on the other hand, are vital for lens protection.

SELENIUM

Selenium (Se) is the most important dictator of glutathione peroxidase activity. Glutathione peroxidase is concentrated in various tissues, besides blood and synovial fluid. In tisues, it operates in the cytoplasm and mitochondria principally. Like catalases, glutathione peroxidase breaks down hydrogen peroxide, besides reducing lipid peroxidation like vitamin E and beta carotene.

Glutathione peroxidase and related enzymes in the retina, plus the precursor amino acids (N-acetylcysteine, L-glycine, and glutamine and selenium) are protective against damage to human retinal pigment epithelium cells. Glutathione peroxidase prevents free radical-induced apoptosis (cell suicide) and helps prevent or treat ARMD.

CAROTENOIDS

DEFINITION

More than 500 distinct compounds are today identified as naturally occurring carotenoids.   They include cyclic hydrocarbon-carotenoids (carotenes), acyclic hydrocarbon carotenoids (lycopene), and oxygenated hydrocarbon carotenoids (xanthophylls like lutein and zeaxanthin).

Handelman and associates noted carotenoids concentration in the macula to be 5-fold higher compared to peripheral retina and 500 times more than the concentration in other tissues. Lutein is the major carotenoid in the peripheral retina, whereas zeaxanthin becomes more and more dominant as the foveal centre is approached. The proportion of lutein to zeaxanthin in macula is 1:2 and the proportion is reversed in the peripheral retina. The distribution of xanthophyll carotenoids suggests a possible role of lutein in protecting the rods and for zeaxanthin in protecting the cones that are concentrated in the central retina. The human lens carotenoids content is 10-20 ng/gm of wet tissue, and the ratio is 1.6:2.2 for Lutein and zeaxanthin.

Another most important dietary antioxidant of ocular significance is lycopene, which is however, conspicuous by its absence in macula. Due to its presence in high concentration in circulating blood in the eye, lycopene plays a prominent role in prevention of macular degeneration mainly by its very potent singlet oxygen quenching capacity.

FOCUS ON CAROTENOIDS IN ARMD

ARMD - INTRODUCTION

In developed countries, ARMD is the leading cause of blindness amongst the elderly (more than 60 years) with a prevalence ranging between 2 to 7% for severe (wet) form and a range of 12 to 30% for the dry form. The disease has caused irreversible visual impairment in an estimated 1.7 million Americans over the age of 65 years. The number of cases of ARMD has been predicted to increase from 2.7 million in 1970 to 7.5 million by the year 2030.

In India, the incidence of ARMD affects approximately 4-5 per cent of the population over the age of 50 years and may be affecting 19-20 per cent of people above 70 years of age. Early disease is characterized by yellowish-colored subretinal drusen. Late disease, which may be 'dry' or 'wet', may lead to significant loss of central vision. Wet form occurs only in 10 percent of population.

ARMD - PATHOPHYSIOLOGY

The light must pass the macular pigment, which contains abundance of zeaxanthin and lutein before striking the photoreceptors. If any damage to the rods and cones is to be prevented the short wave length of light rays (<500 nm range) must be filtered. This is accomplished as follows:

¨       5-286 nm wavelength (ultraviolet C rays): filtered by the earth's ozone layer.

¨       286-320 nm wavelength (ultraviolet B rays): filtered by cornea.

¨       320-400 nm wavelength (ultraviolet C rays): filtered by lens.

¨       400-500 nm wavelength (visible blue light): filtered by lutein / zeaxanthin in macula.

The light entering the retina is between the wavelengths of 400 to 700 nm. The eye would be in perfect focus for daylight only at 560 nm, and even at night 500 nm wavelength of light is optimal for functioning of rods. Hence, filtering out 400-500 nm wavelength of light prevents damage to macula without affecting vision.

Thus macular pigments represent a significant filtering element and hence protect against the light'initiated cumulative oxidative damage. The macular pigment also removes much of the blurry, short wave blue and blue-green light that results from the eye's chromatic aberration. Apart from this the earth's atmosphere through which we view objects almost always contain small-suspended particles, which scatters short wave length light more than other wavelengths and results in a bluish veiling luminance.

The eye and skin are the only structures which have dual exposure to oxygen and light. In presence of blue light (400-500 nm wavelength) the oxygen will be split into singlet oxygen which is one of the most deadly reactive oxygen species as far as the eye is concerned. The blue light has potential to split molecular oxygen due to the high energy contained in it. 

The singlet oxygen and other free radicals formed inside the eye initiate lipid peroxidation of photoreceptors. The polyunsaturated fatty acids in the outer membrane of rods and cones are attacked by free radicals and singlet oxygen species to result in damage of these photoreceptors. As a consequence, there is accumulation of lipofuscin by retinal pigment epithelium which then contributes in druse formation.

ARMD - MEDICAL MANAGEMENT

The damage to macula and formation of drusen can be prevented by filtering out the damaging blue light of the visible spectrum. This is possible by the macula, if its content of lutein and zeaxanthin are adequate. The additional available of lycopene in adequate amounts is of paramount importance in tackling the singlet oxygen single this carotenoids is the best antioxidant known for quenching this reactive oxygen species. In addition, glutathione peroxidase and SOD too have been shown to have preventive benefit in ARMD.

FOCUS OF CAROTENOIDS IN CATARACT

CATARACT - INTRODUCTION

Cataract is a multifactorial disease. Oxidative stress together with weakened antioxidant defense mechanism is attributed to the changes observed in human diabetic cataract. Oxidative damage to the lens has been recognized as a primary event in the pathogenesis of many forms of cataract. Consistent with this view, epidemiological reports have identified factors related to oxidative process that both increase (eg smoking and light exposure) and decrease (eg antioxidant intake) cataract risk.

Epidemiological studies provide evidence that nutritional antioxidants slow down the progression of cataract.

CATARACT - PATHOPHYSIOLOGY

Oxidative stress is high in the eye due to ultraviolet rays which promote liberation of free radicals and singlet oxygen. The epidemiological evidence to support the possibility that lutein and zeaxanthin have an important role in reducing the risk of cataract is somewhat consistent, and justifies the belief in free radical & reactive oxygen species mediated damage to the lens.

Few of the recent studies have stressed the significance of vitamin C, E and selenium in the etiology of cataract. Role of vitamin E has been more specifically stressed by several workers. Low blood levels of vitamin E are associated with approximately twice the risk of both cortical and nuclear cataracts, compared to median or high levels. Smokers are 2.6 times likely to develop posterior subcapsular cataracts more than nonsmokers. Patients with senile cataracts were found to have significantly lower blood and intraocular levels of the mineral selenium than control.

CATARACT - MEDICAL MANAGEMENT

Lower prevalence of nuclear cataract in women or men was associated with intake of lutein and zeaxanthin in high doses. Furthermore, in prospective cohort studies it was noted that people who consumed diet rich in lutein and zeaxanthin, had 20-25 percent lower risk of cataract extraction and 70 percent lower risk of cataract extraction under the age of 65 years.

Experimental study in human lens epithelial cells (HLEC) in culture was evaluated and it was concluded that addition of lycopene had a protective effect to prevent vacuolization of epithelial cells. It was observed that there was as positive effect of retardation of lens opacities due to lutein and zeaxanthin in the aging lenses.

In an 8 year prospective cohort study, Hankinson et al reported that an elevated intake of spinach, which is high in lutein and zeaxanthin (but low in beta carotene content) was most consistently associated with a lower risk of cataract extraction, whereas high beta carotene and vitamin E intakes alone had no beneficial effects against cataract prevention.

This study corroborated data from Jaques et al 1988 who demonstrated that persons with slightly elevated levels of plasma total carotenoids had a 25% lower risk for any type of cataract.

ANTIOXIDANTS IN RETINITS PIGMENTOSA

There is possibility that lutein may slow degeneration of vision in retinitis pigmentosa, a heterogeneous group of slow retinal degenerations. However, only preliminary data in a very small number of patients has been published in which lutein slowed vision loss associated with retinitis pigmentosa in one.

ANTIOXIDANTS IN DIABETIC RETINOPATHY

Several studies are in progress as regards role of antioxidants in diabetic retinopathy and glaucoma but as yet none is conclusive.

CONCLUSION

The overwhelming body of evidence points to significant beneficial effects of nutritional supplementation for most degenerative eye conditions.  Important to remember is that most of the above studies used blood levels and food intakes associated with a normal diet. Taking supplements, specifically containing zeaxanthin, lutein and lycopene in adequate doses, which are theorized to provide protection to macula and lens with adequate doses, may have a much more protective effect than dietary levels alone. With so little risk, and the other potential health benefits from taking nutritional supplements, it would certainly seem prudent to try them, especially for macular degeneration where there are no real options.

Once the damage is done it cannot be reversed (except to a small degree), so prevention and early intervention is essential, especially if we have a family history of the disease. Of course, it’s important to slow further progression at any stage of development. Prevention of lens and macula from the ultraviolet rays and hazard of smoking, however, needs to be over stressed.

DRY EYE SYNDROME

ARE YOU LOOSING SPARKLE IN YOUR EYES?

IF YOU ARE THE ONE WHO LOVE TO SPRINKLE WATER IN YOUR EYES, GET FREQUEST FOREIGN BODY SENSATIONS OR LIKE TO FISH OUT SOME DISCHARGE FROM YOUR EYES, MORE SO IF YOU ARE A LADY, THIS ARTICLE IS FOR YOU.

God had created a mechanism to keep our eyes sparking, moist, free of waste products and infection, and lubricated to make the blinking and winking friction free.

The age, the pollution, the hormonal changes in the body, the exposure to breeze and air-conditioner and professional demand to have staring look at the computer screen etc cause deficiency of tear secretion or excess of evaporation of tears leading to collection of waste products in the conjunctival sac resulting in discomfort, foreign body sensation, irresistible desire to massage the eyes and sprinkle water to remove the waste products.

A unique gland, named lachrymal gland constantly forms the tears which have multiple qualities of nourishment, scavenging, moistening, lubricating and antibacterial.

With the age, the tear formation generally decreases. This change occurs much earlier in ladies due to change in hormones at the menopausal age , i.e, at the age of 40-50 years and a decade later in males. At menopausal age in women, an imbalance occurs between the oestrogen and androgen hormone. Decrease of androgen excites inflammation of lacrimal gland resulting in decreased tear formation.The problem becomes much more intensified when exposed to pollution which causes chronic inflammation of conjunctival sac. With the advancing age the incidence of dry eye is noted in 15-30 percent of the population. In cases of some body inflammation, namely Rheumatoid arthritis, patient's own immune system attacks his lacrimal gland, causing severe dry eye. Systemic drugs like antidepressants, antihypertensives, antihistaminics, anticholinergics, antipsychotics, angiolytics, antiparkinsonians, diuretics and hormones too can cause dry eye. The use of contact lenses and the LASIK surgery for removal of glasses has further swelled the incidence of dry eyes.

Even topically applied drugs which most often have preservatives, can cause dryness of eyes. Glaucoma patients who have to use drugs for long time are more prone to get dry eyes.

Computer Vision Syndrome

Young persons engaged in prolonged computer use, have to stare constantly, which can lead to excess of evaporation of tears ,leading to dry eye sympotoms.This condition is classically called Computer Vision Syndrome. It is advised that the computers are kept at lower level than the eyes, use anti glare screen or Anti Reflect Coated spectacle lenses and develop a habit to blink at least 15-18 times every minute and take some rest at intermittent intervals.

Treatment

Best treatment is to avoid exposure of eyes to pollution, direct wind and breeze of air condioner and any type of over exposure. Topical drugs used should preferably be preservative-free..

Computer users must take precautions as stated earlier.

The best available treatment at present is palliative. Artificial tear drops made with Carboxymethyl Cellulose Sodium.or Hydroxypropylmethyl Cellulose or Sodium Hyaluronate having no preservative, most often relieve all symptoms but the treatment has to be continued for long period. In cases where severe dry eye is suspected, an immunomodulator drug,namely Cyclosporin A drops may be used to treat ocular surface and lacrimal gland inflammation to a significant extent.

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-3 category as food supplements are showing some promising results.

Surgical intervention is indicated in only certain conditions with limited therapeutic advantage.