INTRODUCTION:

Eye development starts in the neural area of the embryo from the mesoderm cells, the middle and outer layer of the blastoderm, and ectoderm cells. Development of eye starts at about the 2^nd week of gestation. In the third week of gestation the optic vesicle, the retina and lens begins to develop. At about 1 month time of gestation the optic stalk which connects to the forebrain and is a precursor to optic nerve starts developing. By this time the iris, colored portion of the eye is also fully developed. Lacrimal gland begins to develop by 6^th week, however tear production starts only after 3 months from birth. At the seventh week sclera is formed and eyelids are still in fused state and by the end of 5^th month the separation of lids occur. By the end of second trimester all the layers of cornea, complete lens, extra ocular muscles are in full form, however orbit even though formed continues to mature till adolescence.

The retinal development starts from 6 months and continues even up to 3 years of age. Even though eye development starts in the 2^nd week of gestation, at birth the eye is only 65% formed and may take 1 more year for complete formation. The requirement and availability of nutrients during the developmental stage itself is an important criteria to ensure visual acuity. Eyes, the most sensitive organ of the human body is being overworked with the dependency on various electronic gadgets. It is mandatory and need of the hour to find ways to prevent our eyes from many preventable disease conditions like the dry eyes. Dry eyes, even though not highly sight threatening leads to significant symptomatic disturbances in our day to day activities. A person might feel tired even after very short exposure to near gadgets once affected by dry eyes. It not only causes visual disturbance with near work but also in all distant and near visual tasks in the long run. Hence we need to look at options to prevent this condition of dry eyes in all age groups.

Understanding Dry Eyes:

Dry Eye Disease:

In the words of DEWS “Dry eye disease is a multifactorial disease of the tear film and ocular surface that results in symptoms of discomfort, visual disturbance and tears film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of tear film and inflammation of ocular surface”.

Symptoms of Dry Eye Disease:

The common symptoms of dry eyes are redness, burning sensation, grittiness, blurring of vision which might be constant or intermittent of. In rare circumstances untreated dry eyes may also result in sight threatening complications.

Prevalence of Dry Eye Disease:

From very few previous studies available it has been established that the prevalence of dry eyes in India varies between 18.4%-40.8%. However population based prevalence data is not available for dry eyes in Indian population.

Tear Film -components and Functions:

A normal tear film consists of three important components:

1. An oily (lipid) component:

It is the outer most layer and is about 0.1um thick. It is formed from the secretions of Meibomian, Zeiss and Moll glands which are present in the eyelids. It consists of low polarity lipids-wax and cholesterol esters, high polarity lipids and phospholipids.

Functions:

· Prevents the overflow of tears.

· Prevents evaporation.

· Limits anterior end of the tear fluid reservoirs

2. A watery (aqueous) component:

It is the Middle layer and formed by secretions from the main and accessory lacrimal glands of Krause and Wolfring. It constitute the main bulk of tear film. It has a thickness of 7-8um over the cornea. It contains inorganic salts, glucose, urea, enzymes, proteins and glycoproteins.

Functions:

· Provides oxygen to corneal epithelium.

· Washes away debris and irritants.

· Contains antibacterial substances namely lysozyme and betalysin.

3. A mucous-like (mucin) component:

It is the innermost layer and is secreted mainly by the conjunctival goblet cells and by the stratified squamous cells of the corneal and conjunctival epithelium. It measures about 0.2um thick.

Functions:

· Plays a vital role in the stability of the tear film.

· Converts the hydrophobic corneal epithelium to a hydrophilic one.

· Lubricates the ocular and palpebral surfaces.

· Provides a slippery coating over the foreign bodies; thereby protecting the cornea and conjunctiva against the abrasive effects of foreign bodies as they move during blinking.

Classification of Dry Eye:

Dry eyes can be broadly classified as aqueous deficient and evaporative dry eyes. This article is limited to the evaporative dry eyes produced majorly by meibomian oil deficiency.

Etiology of Dry Eye:

· Exogenous factors that may be environment induced like decreased humidity, increased winds, air conditioning may lead to dry eyes. Prolonged exposure to electronic gadgets leads to symptoms of dry eyes.

· Etiological factors like increased age and female gender have a predisposition to dry eyes.

· Meibomitis, Inflammation of The Meibomian Gland Plays A Major Role In Causing Dry Eyes.

· Systemic conditions like Sjogren syndrome causes lacrimal gland dysfunction thus leading to dry eyes.

· Dry eyes may also develop in association with viral infections.

· Intake of certain drugs either oral or topical may also induce dry eyes.

· Severe dry eye may occur following bone marrow or stem cell transplants in the presence of graft versus host disease.dry eyes along with dryness of all mucosal membrane is the hallmark of Steven Johnson syndrome.

· Local causes like malposition of lids or facial structures may also lead to dry eyes.

Diagnosis of Dry Eye:

Dry eyes are diagnosed based on the following tear function tests

· Tear Break Up Time (TBUT):

This test evaluates the quality and stability of tear film

· Schirmers test:

This gives a quantitative measure of tears.

· Ocular surface dye staining test:

To evaluate ocular surface disease different dyes like rose Bengal, fluorescein are used.

Nutrition and Dry Eyes:

The research studies have related the role of certain nutraceuticals which possess antioxidant properties like vitamin A, vitamin D, vitamin E, omega 3 fatty acids and omega 6 fatty acids to reduce the severity of dryness.

· Impact of Omega 3 Fatty Acids on Dry Eyes:

Subjects diagnosed with dry eyes when given a supplementation of omega 3 fatty acids showed marked relief in the symptoms and the diagnostic test results also showed some improvements.

According to Bhargava et al. in 2013, A randomized controlled trial of supplementing omega-3 fatty acids for subjects with dry eye syndrome showed that 65% of the patients became asymptomatic and 35% of the subjects showed moderate improvement in symptoms in the dry eyes. The outcomes of tear function tests on day 1 and at the end of 3 months, were compared and was proven to be statistically significant in omega-3 group. A study by Creuzot and colleagues also detected improvement of dry eye relative to symptoms in a placebo controlled randomized trial in a small sample size of subjects on supplementing omega 3 fats. Miljanović et alassessed from the diets of 32,470 women, that those subjects with the higher consumption of omega-3 fatty acids had decreased risk for dry eye. A randomized clinical trial by KC Shih (2017) in on 38 women with Sjögren's syndrome showed improvements in clinical parameters and symptoms score which was in contrast to results obtained in few other studies. It has also been reviewed that the treatment with linoleic and gamma-linolenic acid tablets laterally with eyelid hygiene recovers symptoms of dry eye and condenses eyelid margin inflammation in Meibomian gland dysfunction which is a main cause of dry eye disease instead of treatment with either omega-6 fatty acids or eyelid hygiene alone. Topical application of omega 3 fatty acid in combination with hyaluronic acid in mouse model of experimental dry eye showed significant therapeutic effect on clinical signs of dry eye.

· Impact of Omega 6 Fatty Acids on Dry Eyes:

Omega 6 an important polyunsaturated fatty acid has also been taken for trials for overcoming the symptoms of dry eye. The results of few research studies on omega 6 has been overviewed. A double-masked, randomized controlled trial to evaluate the effect of Linoleic Acid (LA) and Gamma Linoleic Acid (GLA) on chronic ocular inflammation from keratoconjunctivits sicca by Barabino et al found that in 26 patients, oral supplementation with a daily dose of 57mg of LA and 30mg of GLA improved HLA-DR expression as measured by impression cytology, lissamine staining, and symptoms of dry eye, while changes in Schirmer testing and fluorescein break up time (FBUT) were not observed. Also, a study by Aragona et al evaluated the tear film of 40 patients with Sjogren Syndrome for Prostaglandin E1, a downstream product of an anti-inflammatory ecoisanoid, by supplementing with 224mg of LA and 30mg of GLA for a period of one month. A Significant increase in Prostaglandin E1 was observed over one month in the patients who received the omega −6 EFAs (LA and GLA) as compared to the control group. It was also significant that the levels declined to baseline levels when measured 15 days after cessation of therapy and the symptoms were most improved during therapy and worsened after cessation, while the Corneal fluorescein staining remained improved even after treatment was stopped. There was no significant difference in FBUT or basal secretion. An investigation by Kokke et al with 300mg daily dose of GLA in 76 patients with contact-lens-related dry eye syndrome were detected with improvement in dry eye symptoms and tear meniscus height.

· Impact of Vitamin A on Dry Eyes:

A study with 30 men by Saud. A. Alanazi etal. in 2018 with Vitamin A supplementation at a daily dose of 1,500 mg for 3 consecutive days orally showed improved quality of tears in patients with dry eye. Ziada says that oral vitamin A supplement of 3000 IU for 6 months on 40 patients relieved dry eye symptoms, which was diagnosed by Shirmer’s test, and tear break-up time.

The best food sources of Vitamin A are dark green leafy greens like parsley, drumstick leaves, red, yellow and orange coloured foods like sweet potatoes, watermelon, broccoli, carrots, mangoes, and egg yolk when included in the daily diet prevents eye problems of all kinds such as night blindness and dry eye.

· Impact of Vitamin D on Dry Eyes:

Demirci etal. have demonstrated that in 30 vitamin D deficient patients tear osmolarity, Ocular Surface Disease Index and Oxford scale scores were significantly higher and Schirmer I test and TBUT results in the vitamin deficient group were significantly lower than in subjects with normal Vitamin D levels, which means that Vitamin D has strong correlation with dry eye symptoms. Clinical trials by S.H Bae etal. have proved that Vitamin D supplementation using intramuscular injection of cholecalciferol (200,000 IU) for 10 weeks is effective in the management of dry eye syndrome. Hwang et al. in their study on 116 subjects for a period of 1 year have demonstrated that the effect of topical carbomer-based lipid-containing artificial tears and hyaluronate were dependent on serum 25 Hydroxy vitamin D levels. They have also ascertained that Cholecalciferol supplementation enhanced the efficacy of topical treatment and may be a useful adjuvant therapy for patients with dry eye disease.

DISCUSSION:

From various research done we can understand that omega 3 fatty acid has a role to play in the maintenance of tear stability but not in tear production. The studies have shown that the dietary supplementation of omega-3 fatty acids may alter the conformation of meibomian gland secretions and meibum quality in patients suffering from meibomian gland disease and chronic blepharitis leading to stable tear film and thereby decreasing symptoms and signs of dry eye.Omega-3 fatty acids act by modulating the inflammatory process in the eye and nutritional supplementation may have a vital role in dry eye. EPA and DHA modulate prostaglandin metabolism towards anti-inflammatory prostaglandin synthesis due to competitive inhibitions of the arachidonic acid pathway. Inflammation plays a major role in Dry eye syndrome. For example, increased concentrations of cytokines such as interlukin -1, interlukin-6, and tumor necrosis factor -alpha have been found in the tear film of dry eye. The effect of omega 3 fatty acids in the form of topical application in mankind is also being looked into in the research field. Thus, omega-3 and omega-6 fatty acids generate potent modulatory molecules for inflammatory responses, including eicosanoids (prostaglandins, and leukotrienes), and cytokines (interleukins). Preformed GLA present in green leafy vegetables, nuts, vegetable oils, such as evening primrose oil, blackcurrant seed oil, borage oil and hemp seed oil, and from spirulina, cyanobacteria when taken in prescribed amounts in daily diet helps to prevent dry eye symptoms. Lipoic acid, another antioxidant protects eyes from damages due to cataract and dry eyes.

CONCLUSION:

The clinical research done so far is in the primitive stage and the studies are very recent, with respect to confirming the role of nutrients as a preventive or curative measure on dry eyes. There is a lacunae in understanding the, doses required, duration of use recommended especially in Indian population. There is lot of scope for research in this arena which might be fruitful to the society as a whole as, there is very limited research done on this especially in our Indian population to give any conclusive evidence. Anyways, certain available datas as presented above, show a positive trend towards a combined intake of micronutrients especially vitamin A, Vitamin D, Omega 3 and Omega 6 fatty acids as per the Recommended Dietary Allowances and also proper lubrication is required for the maintenance and improvement of eye health.

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Received on 27.12.2019 Modified on 10.02.2020

Research J. Pharm. and Tech. 2020; 13(10):5004-5008.

DOI: 10.5958/0974-360X.2020.00876.8