Dry eye disease is a common condition that can severely impair quality of life. It is a frequent cause of visits to the ophthalmic clinician due to ocular discomfort and visual problems.

Inflammation is now understood to be a key process in the development of dry eye disease. Essential fatty acids have been of interest in the area of dry eye disease treatment due to their anti-inflammatory properties. In this article we examine the role of nutrition on the ocular surface.

In recent years oral supplementation has become more popular with a plethora of dry eye companies now marketing omega-3 based formulations claiming to help relieve dry eye symptoms. Whilst many optometrists are now more confident of recommending supplements for AMD, the concept of supplements for dry eye management hasn’t yet become so widely accepted. The adoption of dry eye supplements is unlikely to be helped by the recent media headlines, following the publication of the results of the DREAM Trial, suggesting that there is no benefit to omega-3 supplements. It is therefore timely to review this subject area and better understand the published literature supporting, as well as challenging, the nutritional benefit of fatty acids for patients who suffer from dry eye disease.

Definition of Dry Eye Disease

Dry eye disease is a result of the eye not producing enough tears, the tears not covering the surface of the eye properly or tears evaporating too quickly. This causes the eyes to become dry, red, and irritated. Symptoms include dryness, grittiness, soreness, burning and temporarily blurred vision.

There are many reasons our eyes become dry, for example, wearing contact lenses, working at a computer screen for long periods, poor diet, air conditioning and heating, inflammatory skin disease (rosacea), inflammatory eyelid disease (blepharitis) or simply growing older.

In 2017, more than 150 dry eye disease experts created a series of recommendations for the management of dry eye disease.

They defined the disease thus: ‘Dry eye is a multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyper- osmolarity, ocular surface inflammation and damage, and neuro- sensory abnormalities play etiological roles.’1

Why is nutrition important?

There are several options for treating dry eye such as artificial tears, heating the eye with a warm compress and massaging the glands in the eyelids, or surgery. Artificial tears are one of the most common methods of treating dry eye; however, they provide temporary relief and do not address the underlying causes.

A dietary supplement with essential fatty acids provides an alternative strategy for relieving the inflammation and symptoms that dry eye disease presents.

A less invasive and more natural method to combat dry eye disease is increasing essential fatty acids in your diet. EPA, DHA and DPA are omega-3 fatty acids essential for the maintaining healthy mucous membranes. They cannot be created in the body and can only be obtained from your diet or supplement. These essential fatty acids are found in the most absorbable format in fish.

Western diets in particular tend to be deficient in omega-3, particularly those derived from fish. A western diet, lacking fish, may promote the development of several chronic diseases, including dry eye.

Increasing your intake of essential fatty acids in your diet can be done by a number of dietary changes. An effective method is to introduce supplements into your daily routine.


Why Omega-3?

Essential fatty acids, especially omega-3, have been shown to improve dry eye symptoms due to their anti-inflammatory capabilities.

Omega-3 fatty acids and omega-6 fatty acids are essential for normal growth and development. omega-3 fatty acids and omega-6 fatty acids compete for the same enzyme to eventually be converted into anti-inflammatory prostaglandins (PGE3) and less inflammatory leukotrienes and into pro-inflammatory prostaglandins (PGE2) and more inflammatory leukotrienes, respectively.

The benefits of Omega-3 supplements has been contested recently


The Importance of Omega-3 (EPA/DHA/DPA)

EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are essential polyunsaturated fatty acids in order to survive. Unfortunately, our bodies are not capable of producing these omega-3 fatty acids on their own. As a result, we depend on our diet to get the necessary omega-3 fatty acids into our bodies.

DHA helps with cell membrane structure and assists in normal growth and development. DHA helps rebuild cell structure on ocular surface after damage due to evaporative dry eye. EPA works as an anti-inflammatory agent for our bodies. Together they provide a number of important health benefits throughout our lifetime.

Recently another marine oil, DPA (docosapentaenoic acid) has been discussed more frequently in the scientific community, as a new and very potent omega-3 fatty acid. This is due to its strong anti-inflammatory properties, even stronger than EPA and DHA.


Omega-6

Excessive amounts of omega 6 fatty acids can promote inflammation, a key step in many chronic diseases such as cardiovascular disease, type 2 diabetes and macular degeneration.

Omega-6 is found in fatty foods made with vegetable oil. Today, we consume at least 20 times more omega-6 than omega-3. The ratio should be 2:1.

Consequently, there is no benefit to using a supplement formulated with omega-6, as generally there is a need to reduce omega-6 intake in order to achieve a more balanced diet.

Omega-7

Omega-7 fatty acid is another polyunsaturated fatty acid that is found in some fish, including anchovy and salmon, as well as olive oil, macadamia nut oil and sea buckthorn oil. Palmitoleic acid is one of the most common forms of omega-7.

Emerging science on omega-7 fatty acids is promising, specifically in regards to lipid metabolism and the maintenance of mucous membranes.

Omega-7 can be helpful at improving lubrication throughout the body, including tears. Omega-7 helps cells retain moisture in the mucous membranes and so helps reduce redness, discomfort and inflammation in dry eyes (figure 1).4

Figure 1: Omega-7 helps retain moisture in the mucous layer


Vitamin D3

It’s becoming common knowledge that vitamin D is important for far more than bone health. New research from the Institute of Ophthalmology at University College London revealed striking eye benefits from vitamin D3 supplementation in older mice, specifically after receiving the supplement for just six weeks.5

 Improvements included:

  • Improved vision
  • Reductions in retinal inflammation and levels of amyloid beta accumulation, which is a hallmark of aging,
  • Significant reductions in retinal macrophage numbers and marked shifts in their morphology (macrophages are immune cells that can cause inflammatory damage).

Oxidative Stability of Fish Oil

The starting ingredients of fish oils are paramount to stability in the end product as marine omega-3 rich oils are highly prone to oxidation to lipid peroxides and other secondary oxidation products.

Oxidized oils may have altered biological activity making them ineffective or harmful. To date, human clinical trials have not reported the oxidative status of the fish oil. This makes it impossible to understand the importance of oxidation to efficacy or harm. However, animal studies show that oxidized lipid products can cause harm.

Increasing the number of manufacturing processes introduces more opportunity for oxidation to occur and therefore, decreases the stability of many omega-3 fish oil supplements. Most omega-3 products are supplied in the ethyl ester form (processed). Some contain omega-3 in the re-esterified triglyceride form (rTG, very processed). The most natural and most stable form of omega fish oil is the natural tri-glyceride form.

Another important aspect of an oral supplement that is not well understood is the influence of the delivery system and its packaging. Gelatine capsules are air and water permeable allowing for oxidation of the contents. Consequently, the only way to ensure that the quality of the last capsule taken is the same as the first one taken from the same supply is to manufacture them in blister packs. Additionally, bottled liquids should be supplied in a light-absorbing bottle and kept refrigerated after opening.


Gelatine capsules are permeable, allowing oxidation of the contents


Recent studies

The recent study, the DREAM trial , reports that omega-3 is no better than a placebo in relieving the symptoms of dry eye disease. The placebo used in this study is olive oil. However, olive oil has many nutritional benefits and in fact contains omega-7, which is an anti-inflammatory and can help maintain moisture in the mucous membranes, and so helps reduce the symptoms of dry eye. Olive oil should not have been used as a placebo.

Secondly, for this trial, the study participants were given ultra-concentrated omega supplements. Most omega-3 supplements are concentrated, (esterified or re-esterified tri-glyceride). As already discussed, increasing the number of manufacturing processes has a detrimental effect on the stability of fish oil and so a highly processed omega-3 fish oil supplement may in fact provide very little benefit for the dry eye participant.

It must also be noted that both the supplement group and the placebo group had an improvement in the group’s mean OSDI (Ocular Surface Disease Index) score (-13.9 points and -12.5 points respectively) and it is this difference that was not statistically significant. However, it can be argued that this could be seen as clinically significant. Finally, the participants were free to use any combination of dry eye drops during the study that could have influenced the results.7


Discussion

It is widely accepted that the best way of achieving balanced nutrition is through a balanced diet and in the case of obtaining essential fatty acids, such as omega-3, is to incorporate regular portions of oily fish in the diet. The reality is that for most dry eye patients with modern busy lifestyles, who are already ingesting too much omega 6, this means taking omega-3 supplements in order to try to rebalance their intake to be nearer the 2:1 ratio.

However, the source and production of the supplement is particularly important in its ultimate effectiveness. Broadly speaking the closer to the natural tri-glyceride form (as found in fresh fish) the omega-3 is, the more stable it is and the higher its nutritional content. Blister packaging the capsules will further protect the oil from any oxidation altering its biological activity within its stated shelf life.

Anyone who has ever wondered about the fishy smell given off by fish oils (and/or been put off taking them) should think about the fact that fresh fish has no odour; it only starts to smell as it degrades with aging. This is effectively what happens when supplements degrade through oxidation, due either to over processing during its manufacture or exposure of the product to the air and light post manufacture.

One good recent example of a highly stable, natural tri-glyceride omega-3 dry eye supplement is Eye Nutrients Dry Omega. Eye Nutrients uses naturally sourced omega oils (triglycerides) with the natural antioxidants contained in olive oil. These natural antioxidants have a significantly greater effect on maintaining the stability of the omega-3 molecules and also impart additional benefits to health. This is available in blister-packaged, fish gelatine, capsules and a bottled liquid form.

Dry Omega delivers natural fish oil in a liquid or fish gelatine capsule


Conclusion

Dry eye disease is a multifactorial disease, with differing levels of severity and symptoms. Treatment regimens should address the multifactorial nature and differing patient requirements.

It is not enough simply to provide artificial tears, a clinician must assess the patient’s ocular surface and determine if improved nutrition, involving omega-3 supplementation, should be used as part of a complete treatment regime.

In dry eye disease, the advantages of essential fatty acids are threefold:

  1. restoration of the lipid layer
  2. decreased inflammation and apoptosis
  3. increased tear secretion

There are many nutritional omega-3 supplements available to purchase through opticians, pharmacies, retailers and online. However, they are not all the same. The most effective and safest forms of omega-3 are the natural tri-glyceride form, which is the least processed and most stable.

Professor Johnny Moore is a consultant ophthalmologist based at Mater Hospital, Belfast Trust, Ireland. Dr Eric Pazo is a researcher from the Biomedical Sciences Research Institute, Ulster University based at the Cathedral Eye Clinic.


References

  1. The Dry Eye Assessment and Management Study Research Group. Omega-3 fatty acid supplementation for treatment of dry eye disease. N Engl J Med. Published online April 13, 2018.
  2. J.Craig et al. “TFOS DEWS II Definition and Classification Report” The Ocular Surface 15 (2017) 575 – 628.
  3. Bhargava R1, Kumar P2, Kumar M3, et al. “Omega-3 Fatty Acids have a Definite Role for Dry Eye Syndrome”. A randomized controlled trial of omega-3 fatty acids in dry eye syndrome. Int J Ophthalmol. 2013 Dec 18;6(6):811-6.
  4. Larmo et al. Oral Sea Buckthorn Oil Attenuates Tear Film Osmolarity and Symptoms in Individuals with Dry Eye. June 16, 2010. The Journal of Nutrition
  5. V Lee, E Rekhi, JH Kam, G Jeffrey. Vitamin D rejuvenates ageing eyes by reducing inflammation ,clearing amyloid beta and improving visual function. Neurobiology of Aging 2011.12.002.
  6. Albert et al. Oxidation of Marine omega-3 Supplements and Human Health. BioMed Research International Review Article. Volume 2013 (2013)
  7. The Dry Eye Assessment and Management Study Research Group. omega-3 fatty acid supplementation for treatment of dry eye disease. N Engl J Med. Published online April 13, 2018.
  8. Essential fatty acids for dry eye: A review. Marco Roncone, Hannah Bartlett, Frank Eperjesi. Contact Lens & Anterior Eye 33 (2010) 49–54