An Overview on the Sway of Nutritional Supplements on Dry Eye Disease: Analysis of Tear Production

Abstract

Dry eye disease is gaining attention in the field of health and eye care research lately. With the advent of electronic gadgets, dry eyes are becoming more prevalent and require immediate attention both in adults and children. Children from the infancy are exposed to near gadgets like mobile phones and tabs, when we consider their life span and the time that would be spent on these devices leaves us concerned and worried regarding the visual demand and misuse of eyes. Prevention being better than cure leads us to consider the role of dietary essentials as a potential option to prevent from dry eyes. There are various reasons for dry eyes and this review is carried out with the aim of throwing light on the dry eye due to evaporative loss of tears which may or may not be associated with inflammatory conditions and the impact of powerful dietary supplements like vitamin A, vitamin D, omega 3 fatty acids and omega 6 fatty acids on dry eye.

1. Key Words: Antioxidants, Dry eye disease, Nutraceuticals, Omega 3 fatty acids, Omega 6 fatty acids, Tear film, Vitamin A, Vitamin D.

2. 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 2nd week of gestation. In the third week of gestation the optic vesicle, the retina, and lens begin 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 6th 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 by the end of 5th month the separation of lids occur. By the end of second trimester all the layers of cornea, complete lens, and extraocular 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 2nd 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 lead 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.

2. Understanding dry eyes

2.1 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”.

2.2 Symptoms of Dry Eye Disease

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

2.3 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 the Indian population.

2.4 Tear Film -components and Functions

A normal tear film consists of three important components:

• 1. An oily (lipid) component

It is the outermost 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:

1. Prevents the overflow of tears.
2. Prevents evaporation.
3. Limits anterior end of the tear fluid reservoirs

• 2. A watery (aqueous) component

It is the Middle layer and is formed by secretions from the main and accessory lacrimal glands of Krause and Wolfring. It constitutes 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:

1. Provides oxygen to corneal epithelium.
2. Washes away debris and irritants.
3. Contains antibacterial substances namely lysozyme and beta lysin.

• 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:

1. Plays a vital role in the stability of the tear film.
2. Converts the hydrophobic corneal epithelium to a hydrophilic one.
3. Lubricates the ocular and palpebral surfaces.
4. 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.

2.5 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.

2.6 Etiology of Dry Eye

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

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• 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.

3. 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, and fluorescein are used.

4. 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.

4.1 Impact of Omega 3 Fatty Acids on Dry Eyes

Subjects diagnosed with dry eyes when given 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 omega-3 fatty acids in dry eye syndrome showed that 65% of the symptomatic patients were asymptomatic and 35% had moderate improvement in symptoms in the omega-3 group. 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. Creuzot and colleagues also observed improvement of dry eye relative to symptoms in a placebo-controlled randomized trial in a small sample size of subjects. Miljanović et al assessed the diets of 32,470 women and found that those with higher omega-3 fatty acids consumption 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 scores which was in contrast to results obtained in few other studies. Therapy with linoleic and gamma-linolenic acid tablets along with eyelid hygiene improves symptoms and reduces eyelid margin inflammation in Meibomian gland dysfunction which is a main cause of dry eye disease more than 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.

4.2 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 keratoconjunctivitis 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 a 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.

4.3 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.

4.4 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.

5. 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.

It is likely that dietary supplementation of omega-3 fatty acids alters the composition of meibomian gland secretions and meibum quality in patients with meibomian gland disease and chronic blepharitis leading to stability of 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, interleukin-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.

6. 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 the 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 toward 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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Ref No: IJSTR-0220-30537