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Patients with dry eye disease suffer from chronic ocular discomfort and variable visual disturbances.

Up to 38 per cent of the general population suffers from a degree of dry eye, according to the latest figures from the American Academy of Ophthalmology presented in Chicago in 2012. There is a dry eye epidemic in people aged between 15 and 25 years due to the extensive use of amartphones, video games, tablets, etc. More than 50 per cent of the presbyopic population is affected. This means that, overall, more than 50 per cent of opticans’ customers would greatly benefit from an effective treatment to alleviate their symptoms and improve their quality of life.

Although the causes of dry eye are varied, evidence supports chronic inflammation as a common underlying factor. As a matter of fact, conjunctival inflammation is a hallmark of all dry eye syndromes. Studies using immunological techniques have indeed shown the presence of conjunctival inflammation in more than 80 per cent of patients with eye dryness. The inflammation may be pre-existing and induce dryness. Clinical studies have also shown oxidative reactions in the tear fluid of patients suffering from dry eyes.

The inflammation may be aggravated by exogenous factors such as pollution and local infection; it may be associated with allergic reaction or meibomian gland diseases, or it may appear after administration of allergenic treatments, especially those containing preservatives. Nevertheless, once dry eye disease has developed, inflammation associated with oxidative stress becomes the key mechanism of ocular surface injury, as both the cause and consequence of cell damage. Patients with severe dry eye disease thus find themselves trapped in a vicious circle of inflammation, oxidative stress and ocular surface injury.

Recently, there has been a great deal of interest generated by the use of more natural but still scientific and efficient remedies – polyunsaturated fatty acids (PUFAs), vitamins and other types of antioxidants – in the treatment of dry eye disease. In other diseases, PUFAs have been shown to play a role in inflammatory processes leading to the pathologic changes that are observed, such as atherosclerotic heart disease. What do we know about these ingredients?

Gamma linolenic acid (GLA)

GLA is categorised as an omega-6 fatty acid and is obtained from vegetable oils such as borage oil, blackcurrant seed oil and evening primrose oil. Each contains varying amounts of GLA: borage oil ranges from 20 to 26 per cent, blackcurrant oil ranges from 15 to 18 per cent, and evening primrose oil ranges from eight to 10 per cent GLA. The human body produces GLA from linoleic acid (LA). Nevertheless, reaction is quite slow and its efficacy is limited with the intake of alcohol, tobacco and saturated fatty acids. Diseases such as high blood pressure, diabetes, arthritis and psoriasis can also limit the activity of the delta-6-desaturase enzyme, which coverts linoleic acid into GLA.

Clinical studies report that GLA reduces symptoms and calms inflammation in people with dry eye, and improves symptoms and increases tear production in people undergoing corrective laser procedures. It also reduces symptoms and increases anti-inflammatory prostaglandin levels in those with Sjögren’s syndrome.

GLA is rapidly converted to dihomo GLA (DGLA), which leads to a significant increase of the anti-inflammatory prostaglandin E1 that supports normal tear secretion. DGLA competes with arachidonic acid for the enzymes, COX and LOX. Arachidonic acid is the omega-6 found abundantly in meat and dairy produce, and the precursor to pro-inflammatory prostaglandin E2 DGLA, therefore, it reduces the inflammatory properties of the prostaglandin E2.

Eicosapentaenoic  acid (EPA)

EPA is an essential omega-3 fatty acid. It is obtained in the human diet by eating oily fish or fish oil, e.g. cod liver, herring, mackerel, salmon, anchovies and sardine. Clinical studies showed that higher intake of EPA may reduce the risk of dry eye in women, in addition to providing well-established cardiovascular benefits.

EPA is a precursor to anti-inflammatory eicosanoids, prostaglandin E3 (PGE3) and leukotriene B5, which regulate and decrease the inflammatory processes. These eicosanoids also raise meibomian secretions and, therefore, indirectly promote the pre-corneal tear film. EPA also promotes the PGE1 secretion and, therefore, stimulates the overall tear secretion.

EPA is an essential omega-3 fatty acid obtained in the human diet by eating oily fish like salmon.

EPA and GLA: a synergy of action

One concern related to GLA and DGLA, is that it could be further metabolised to arachidonic acid with subsequent pro-inflammatory effects. Human studies have demonstrated that the addition of fish-derived omega- 3 EPA, in a balanced ratio to GLA, blocks the activity of delat-5-desaturase and prevents elevations in serum arachidonic acid.

Co-ingesting EPA and GLA increase cellular membrane content of both DGLA and EPA (precursor). This supplementation strategy successfully maintains the anti-inflammatory capacity of GLA and increases serum EPA, without causing accumulation of the pro-inflammatory arachidonic acid.

Alpha lipoic acid (ALA)

ALA is a fat and water-soluble antioxidant, which diffuses easily in the whole ocular tissue. It can be found in broccoli and spinach in very small quantities. ALA scavenges reactive oxygen species and helps recharge other antioxidants, such as glutathione, vitamin C and vitamin E. This tends to increase the goblet cell population density and stabilise the pre-corneal tear film. ALA also promotes the lachrymal glands secretions by modulating and decreasing some of the inflammation mediators, such as the NF-kappa B transcription factor

Ingredients and formulation

Is it enough to get the right ingredients with the right dosage? A well- written menu is not enough to guarantee a good meal in a restaurant. The quality of the chef, and the quality and the freshness of the ingredients, are obviously equally important if not more important. Likewise, a good formulation is not enough to guarantee the optimal efficacy of a food supplement.

It is of the utmost importance to guarantee the high quality of the carefully chosen ingredients. This high quality is a guarantee of the ingredients’ efficacy. These ingredients, and especially omega-3 from fish oil, must also be very carefully protected from oxidation. This is particularly important, as oxidation rapidly transform the ‘good’ omega-3 into potentially harmful oxidised lipids. Not only would the omega-3 become ineffective, but the final product would become difficult to digest and present a disagreeable smell. Note: fresh fish does not smell.

Is the formulation of the finished product, and the origin of the ingredient, important? Yes, of course. The Galenic formulation dictates that softgels must be isolated and protected from each other in blisters. They should not be in jars in order to avoid water transfers between softgels, which promotes fish oil oxidation. Metallic ions (e.g. zinc, copper, iron) promote oxidation. When present in formulations, these must be isolated from the oil, with a microencapsulation technique, for example.

Ingredients must preferably bear a label in order to guarantee their quality. It is important to ensure that fish oil comes from fatty fish from sea with a very low degree of pollution. Fish oil must be extracted as quickly as possible and placed under nitrogen in order to avoid oxidation. The softgel gelatine coating must also show its origin. Non-specified origin generally means either a porcine (the cheapest) or a bovine origin.

Lagad Lacrima

Lagad Lacrima is a dual-action supplement consisting of antioxidants, vitamins, minerals and essential fatty acids to improve the nutrition of the cornea and maintain the comfort of the tear film, promoting the production of tears through GLA (gamma linoleic acid) from Borage oil and EPA, a polyunsaturated fatty acid omega-3 oil from cold water fish. Lacrima reduces the need for comfort drops in most cases.

The formula for Lagad Lacrima was developed based on the work of ophthalmologists and nutritionists who specialise in research in dry eye. It largely reduces the need for drops. Recommended usage is two softgels a day for two months, followed by a one-month break in order to maximise the effectiveness and cost to the patient.

Lagad Lacrima: an omega-3 based supplement for dry eyes