research review

Essential Fatty Acids and Dry Eye: What Do We Know?

BY LYNDON JONES, PHD, FCOPTOM, FAAO

The recent reclassification of dry eye as a disease that is accompanied by ocular surface inflammation has led clinicians and researchers to look for methods to alleviate the often subtle levels of inflammation that co-exist with common signs and symptoms.

In severe dry eye, the inflammation is widespread and may require managing with steroids, but we must avoid long-term steroid use due to their known side effects. Newer site-specific steroids or NSAIDs may prevent these long-term issues. These or other anti-inflammatory agents such as Restasis (cyclosporine, Allergan) when used with lubrication have proven highly effective in managing moderate-to-severe dry eye. However, what about more subtle dry eye cases?

Growing evidence shows that nutritional supplementation with essential fatty acids (EFAs) may play a significant role in managing ocular surface dryness. EFAs are involved in a variety of biological processes. They cannot be synthesized in the body and must be ingested through diet or via supplementation.

There are four different kinds of fats in food: cholesterol, mo-nounsaturated fat, polyunsaturated fat, and saturated fat. EFAs are an example of long-chain polyunsaturated fatty acids (PUFAs). Within this group, EFAs have two distinct subclasses — omega-3 and omega-6 fats. Examples of omega-3 PUFAs are alphalinolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is the precursor to EPA and DHA. The omega-6 PUFA family includes linoleic acid (LA), gammalinolenic acid (GLA), and arachidonic acid (ARA).

The Process of Inflammation

To understand the relevance of EFAs to dry eye, we need to look at the processes involved in inflammation and consider the family of signaling molecules called the eicosanoids. There are four basic sub-classes of eicosanoid, namely leukotrienes and three types of prostanoids: prostaglandins, prostacyclins, and thromboxanes. All are made via oxygenation of the EFAs.

Two families of enzymes catalyze the EFAs to produce the eicosanoids: lipoxygenase generates the leukotrienes and cyclooxygenase generates the prostanoids. The eicosanoids exert complex control over many bodily systems, particularly during inflammation or immunity, and act as messengers in the central nervous system.

The eicosanoids form in response to mechanical trauma, the presence of various cytokines, growth factors, or other stimuli. Omega-6 eicosanoids are generally pro-inflammatory while omega-3s are much less so. For example, the omega-6 EFA ARA sits at the head of the arachidonic acid cascade, which results in inflammation. The omega-3 EFA EPA reduces the inflammatory effects of ARA.

The amounts and balance of these EFAs in a person's diet will affect the body's eicosanoid-controlled functions, with resultant effects on cardiovascular disease, triglycerides, blood pressure, and arthritis. Thus, if a patient were to produce an increased amount of vigorously pro-inflammatory omega-6-derived eicosanoids, this would adversely affect the local cellular environment resulting in increased local inflammation, as seen in some forms of dry eye.

Notably, anti-inflammatory drugs, which work locally in dry eye, act by down-regulating eicosanoid synthesis.

Dietary Effects on Inflammation

It is clear that an intake of both omega-3 and omega-6 EFAs is essential, and it would appear that overall omega-6 intake should be restricted if the pro-inflammatory omega-6 eicosanoids are to be restricted in their function. Omega-3 EFAs such as ALA are found in foods such as flaxseed or linseed oil, leafy green vegetables, and various types of vegetable oils. Other omega-3 EFAs such as DHA and EPA can be obtained by consuming oily, coldwater fish such as halibut, herring, and tuna. Buffalo, venison, and walnuts are also rich in omega-3. Omega-3 fatty acids are also attainable from fish oils, which are available in capsule form. Omega-6 EFAs are found abundantly in meat, evening primrose oil, canola and corn oil, and margarine.

Research suggests that an ideal omega-3:omega-6 ratio would be 1:1 to 1:3 in favor of omega-6. However, a typical Western diet is over-rich in omega-6-containing foods, with studies suggesting that the ratio is closer to 10-to-20 to 1 in favor of omega-6 due to overconsumption of meat and fried foods, with attendant increases in cardiac disease and arthritis.

Another approach to reducing overall omega-6 intake involves increasing intake of certain antiinflammatory omega-6 EFA supplements. GLA, found in high concentration in oils derived from evening primrose, has antiinflammatory properties. GLA elevates dihomo-g-linolenic acid concentrations, leading to an increased synthesis of prostaglandins that have a positive role in chronic inflammation. Studies have demonstrated that dietary supplementation with GLA may relieve chronic inflammation in systemic diseases such as rheumatoid arthritis.

Reducing Dry Eye Symptoms

So, what peer-reviewed evidence exists that manipulating the intake of EFAs can reduce dry eye symptoms? Early evidence from Oxholm and co-workers (1998) showed that DHA was inversely correlated with dry eye symptoms, suggesting a protective role for that omega-3 EFA. Key evidence arose from the study by Miljanovic and colleagues (2005), who analyzed data from more than 30,000 women enrolled as part of the Women's Health Study. They showed that women who consumed the highest amounts of omega-3 fats (primarily from tuna) had the lowest rate of dry eye syndrome.

What about the omega-6 EFAs? Two randomized clinical trials demonstrated that oral supplementation with LA and GLA ameliorated dry eye signs and symptoms. Other work has shown that targeted omega-6 intake may help with managing dry eye in symptomatic contact lens wearers and in those undergoing refractive surgery. Macri and colleagues (2003) demonstrated that a once-daily dose of LA plus GLA had a positive effect on both tear function tests and ocular symptoms.

The meibomian glands' role in dry eye disease is well established, and recent work has suggested that PUFA intake has a positive role in healthy meibomian gland function. Finally, recent data on mice suggests that topical EFA administration in eye drop form can alleviate typical inflammatory changes seen in dry eye.

Thus, evidence continues to accumulate of the positive role that diet can play in managing various forms of dry eye.

Advising patients to limit their omega-6 intake and to keep their ratio of omega 3:omega 6 intake to less than 1:3 may help minimize both signs and symptoms of dry eye. Patients can achieve this by consuming increased amounts of oily fish and minimizing fatty foods and meat.

If patients do not like to eat fish, recommend a daily gel-cap supplement of PUFA, specifically containing DHA and EPA from fish or flaxseed oil.

One controversial issue to consider relates to the known contamination of fresh coldwater fish with poisons such as methyl mercury and pesticides, resulting in a recommendation that individuals, particularly pregnant women and children, should consume fish no more than three times a week. To overcome such problems, products such as TheraTears Nutrition for Eye Comfort (Advanced Vision Research) are now guaranteed by their manufacturers to contain omega-3s sourced from mercury-free fish oil.

One issue under investigation relates to the increased clotting time induced by high levels of PUFA intake, which may be of concern to those concurrently taking anticoagulants.

Managing Dry Eye Patients

Practitioners continue to deal with significant numbers of patients who have signs and symptoms of dry eye. Advice on the positive benefits of EFAs in addition to other advice such as lid hygiene will add further to our ability to manage these challenging patients. CLS

For references, please visit www.clspectrum.com/references.asp and click on document #164.

Dr. Jones is the associate director of the Centre for Contact Lens Research and a professor at the School of Optometry at the University of Waterloo, Ontario, Canada. He has received research funding from Alcon, AMO, B&L, CIBA Vision, CooperVision, Johnson & Johnson, and Menicon.