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The role for nutrition in dry eye disease.

Course code: C-38788 Deadline: December 26, 2014

Learning objectives

To be able to explain to patients about the importance of nutrition in relation to dry eye disease (Group 1.2.4)

To be able to manage patients with dry eye disease (Group 6.1.3)

Learning objectives

To be able to explain to patients about the importance of nutrition in relation to dry eye disease (Group 1.2.4)

To understand the role of nutrition in the management of dry eye disease (Group 8.1.3)

Learning objectives

To be able to explain to patients about the importance of nutrition in relation to dry eye disease (Group 1.2.4)

To understand the role of nutrition in the management of dry eye disease (Group 5.4.2)

Learning objectives

To understand the role of nutrition in the management of dry eye disease (Group 1.1.2)

To understand the option for using nutritional supplementation to manage dry eye disease (Group 2.1.6)

Background

The number of people around the world with dry eye symptoms is growing at almost 3% per year and it is estimated that there will be 250 million people suffering with symptoms by 2022. (1) In the UK we would estimate the prevalence to be approximately one in five adults, (2) but this relates to people with a fulltime diagnosis and probably represents the tip of the iceberg. Many more people may be affected by what we would call 'episodic' dry eye, due to factors such as working on computers or tablets, wearing soft contact lenses, or exposure to air conditioning. A recent study has shown that one in 10 British women have been diagnosed with dry eye disease, but one in five had experienced symptoms within the previous three months. (3) The prevalence of dry eye problems increases with every decade, and it remains one of the most common eye complaints of the elderly. (4,5)

The profile of what we eat has changed drastically over the last 100 years with innovation in food production processes. There is a significant increase in the amount of fat in our diets, a decrease in vitamins, and a change in where we get our course of dietary fat, from omega-3 fatty acids to omega-6 fatty acids. (6) So, it is not surprising that there are huge implications for health.

With this perspective, you would imagine we would have found effective solutions to manage dry eye disease, but there is still much to learn. The Dry Eye Workshop (DEWS) report in 2007 defined the condition as a vicious circle of inflammation (see Figure 1), leading to damage to the ocular surface. The goal of any management plan is to get the patient out of this loop by addressing the balance/ stability of the tears, and/or the inflammation. The meibomian gland dysfunction (MGD) report (2011) further reviewed and defined the significant role for MGD in over 80% of dry eye diagnoses. (7)

The understanding of the significance of MGD as the trigger for so much dry eye is changing the emphasis we put on the eyelid examination in such patients. In fact, if you find yourself about to recommend eye drops without lid care, then you may be missing the underlying cause of the problem in most people. But perhaps, most importantly, increased understanding has opened up new options for relief from symptoms and signs.

Meibum is the major source of the lipid layer for the tear film (see Figure 2), but it is very complex in composition; the addition of a lipid or oil in several modern dry eye products is a welcome development but a relatively poor substitute (chemically) for the real thing.

So, how do you stop the meibomian glands from becoming dysfunctional in the first place, and how do you maintain their optimum condition?

Keeping eyelids healthy is supported by three components; keeping them clean, blinking enough and a healthy diet. Lid hygiene is key because an excess of Staphylococci on the eyelid margin is directly influential in MGD. These bacteria produce lipases, enzymes which break down meibum lipids--a saponification process--giving rise to foamy tears, and for some, a stinging sensation. Indeed, this is why baby shampoo is detrimental to the tear film. Once the tear film is disrupted, then the patient enters into this vicious circle where tear film instability leads to hyperosmolarity of the tear film and subsequent ocular surface inflammation, and so it goes on. Insufficient blinking, which can result from computer or smartphone usage increases the osmolarity of the tear film and is believed to directly impact the epithelium around the openings to the ducts of the meibomian glands. 8 Indeed, computer users tend to have lower mucin concentration in their tears, (9) and the prevalence of MGD in symptomatic computer users can be in excess of 74%. (10)

The meibomian glands are mostly under hormonal control, particularly androgens, and they also have a neural innervation, unlike sebaceous glands in the skin. The androgens affect the development, the control and also the lipid production Itself. When androgens are deficient, as occurs with general ageing, or in conditions such as Parkinson's disease, MGD is much more prevalent. Oestrogen therapy for menopausal symptoms also reduces lipid production, and promotes MGD and evaporative dry eye symptoms. (11)

Evidence of the role of nutrition

Scientific evidence about the effect diet has on the prevalence and incidence of eye disease comes from a wide variety of sources, and some is more robust than others. Evidence about the health benefits of dietary intake tends to come from two types of research:

* The observational study of large populations and their dietary intake, and their association with disease. Such as population studies with Inuit, Mediterranean, or Nordic participants

* Pros: Large samples

* Cons: Relies on food diaries mostly

* The studies where an intervention is applied and the people followed for a period of time - the most robust being randomised controlled trials against a placebo

* Pros: More control?

* Cons: Volunteers tend to be health-conscious so not perhaps people who benefit most; compliance may be poor; people drop out.

A big challenge in nutrition research is that observing people's dietary intake does not reveal what they store internally--in the liver or in blood plasma for example--and unpopular invasive measures are needed to assess this. There is a recent (2013) excellent scientific review about the tear film that acknowledges the evidence from epidemiological studies to conclude that there is a likely to be a beneficial effect from oral dietary supplements, but that we still have a lot to learn about composition, dosage and mode of action. (12)

How can diet influence dry eye signs and symptoms?

A healthy lifestyle is important generally.

A poor diet accelerates the ageing process through the production of free radicals and not enough anti-oxidants to absorb them, leading to cellular damage. Smoking has been linked to an increased risk of dry eye due to detrimental effects on the ocular surface, (13) and lacrimal gland. (14) Calorie restriction (avoiding obesity) is thought to reduce the risk of dry eye; it has been shown to improve lacrimal gland function in animal models. (15) Having diabetes also increases the likelihood of having dry eye, (16) and poor diabetic control is associated with a sub-optimal tear film, even in the absence of dry eye symptoms. (17) Whole-body hydration may be an important consideration for the tear film. A recent investigation suggested that dry eye subjects have higher plasma osmolarity than non-dry eye subjects. (18)

The benefits of polyunsaturated fatty acids (PUFAs) in maintaining healthy cholesterol levels and lowering the risk of heart disease are well known, but they also play a part in dry eye. PUFAs are classified into the omega-3 and omega-6 groups--both are termed essential fatty acids (EFAs), meaning we can't produce them and they are required for many core body processes including inflammation, maintaining healthy cells and brain function. Research has shown that dietary intake of omega-3 fatty acids and the ratio of their consumption to that of omega-6 affects the overall amount of inflammatory activity in the body. (19) It is not quite as simple as the media may suggest: tabloid headlines of 'omega-3 is good' and 'omega-6 is bad' are misleading. Omega-3 acids are almost always converted into anti-inflammatory mediators, but omega-6 can lead to either pro-or anti-inflammatory effects depending on the dietary source and the complementary intake of omega-3. This is because the metabolic processes for both fatty acids compete for the same enzymes (see Figure 3), and a balanced intake is important to control inflammation.

The ideal intake ratio of omega-3 to omega-6 would be around 1:3, but in the UK it is typically 1:15. Large, epidemiological studies have demonstrated a significant decrease in the risk of dry eye in populations with a high intake of omega-3. One large study on over 32,000 women found that those with a higher dietary intake of omega-3 have a lower prevalence of dry eye, including a 68% lower prevalence in women who consumed 5-6 servings of tuna fish each week, compared with the women who consumed 1 serving per week. A high omega-6:omega-3 ratio (that is >15:1) was associated with a more than two-fold greater prevalence of dry eye than was seen with a low ratio (4:1). (20) Unfortunately, as a nation we tend to prefer white fish like cod over better sources of omega-3 like salmon and mackerel. Salmon has about 10x the available amount of omega-3 compared to cod.

It is logical therefore, that supplementation might be beneficial. Flaxseeds are a source of omega-3, but its conversion in the body to EPA and DHA is inefficient and slow, while fish oils represent a more efficient source. The commercially available products vary in quality--fish oil capsules are easily oxidised by light or moisture so premium products tend to be opaque capsules in individual blisters within a lightproof box or jar--a good guide for consumers. Also, the origin of the fish oil is important: fish from unpolluted seas and sophisticated purification processes are desirable, and are normally only found in pharmaceutical grade products. Cod liver oil, while not as rich as other fish oil, is a good course of omega 3 (our grandparents may have been right after all) and it also contains vitamins A, D and E. Krill oil comes from the plentiful tiny crustaceans in the Antarctic Ocean but contains relatively low levels of EPA and DHA. There is some debate about which is the best form for easier digestion because they can be triglycerides, ethyl esters, phospholipids or free fatty acids. The structure and breakdown of these various forms of essential fats differs: yielding the same omega-3 EFAs, but the efficiency in how the body can utilise them varies, termed 'bioavailability'. Ethyl esters tend to be cheaper than others, but the least bioavailable form (compared to triglycerides, phospholipids and whole fish), oxidising easily. (21,22) Patients might think that taking more of a cheaper supplement is a logical approach, but there are a lot of extra calories in such consumption of fish oil capsules. There are alternatives for those wishing to avoid fish products or gelatin capsules--sources of omega-3 derived from sea algae have also been shown to help dry eyes over a three month period compared to a placebo. (23)

In several published clinical studies, the direct benefits of supplementation with omega-3 and omega-6 in dry eye are convincingly consistent. Small, randomised trials, as well as animal data, suggest beneficial effects of these EFAs on the ocular surface in dry eye. (24-27) Effects of supplementation have been seen in as little as one month - in a randomised, double-masked trial on 64 patients taking omega-3, improvements were seen in symptoms, tear film stability and Schirmer test after just thirty days. (28) Evening primrose oil (GLA, an omega-6 EFA) provides a beneficial effect in alleviating dry eye symptoms and improving overall comfort in patients suffering from contact lens-associated dry eye, compared to an olive oil placebo. (29)

Increased anti-inflammatory prostaglandins have been detected in tear samples from patients with Sjogren's syndrome who have taken omega-6 supplementation as well as observed improvements in signs and symptoms. (30)

In summary, omega-3 intake is associated with improved secretions from the meibomian glands and increased tear film stability, (31) decreased inflammation and apoptosis and increased secretion, while omega-6 (GLA) intake appears to increase tear production. (32)

There remains a somewhat unproven risk about omega-3 supplementation: theoretically, an excess of omega-3 EFAs could cause bleeding due to their anti-clotting properties, therefore, individuals who suffer from bleeding disorders should always talk to their GP before taking such supplements. There is no official recommended dietary allowance (RDA) for these compounds due to lack of dose-related research, so we can only refer to the recommended intake for coronary health where there is a generally accepted level of 1g per day (EPA + DHA). And it's worth remembering that when the packaging says 1000mg on the front, not all of that will be omega-3 as that is purely the weight of the capsule--you have to look to the EPA/DHA content written elsewhere on the packaging.

What about vitamins and minerals?

Vitamins and minerals play a part in the relief of dry eye symptoms too. They can protect cells from oxidative damage in their own right (as antioxidants), but are often included in supplements containing EFAs, for example Vitamin E, to protect the EFAs from oxidation, and because they work in synergy with the enzymes that metabolise the EFAs in the body. Antioxidant complexes, for example, beta-carotene, vitamins E, C, B, B6, D, zinc and copper given to patients with marginal dry eye have demonstrated improved tear film stability and goblet cell density, (33) and reduced symptoms. (34) Adequate vitamin A is certainly needed in the diet for tear secretion and mucin production, and while the beneficial effects are clear in cases of malnutrition, the benefits within the range of normal health is less clear.

Does a healthy diet impact the meibomian glands directly?

Supplementing omega-3 fatty acids encourages the production of anti-inflammatory prostaglandins and modifies the composition of meibomian lipids. (35,36) The glands directly utilise omega-3 EFAs as part of lipid synthesis towards meibum. A randomised, placebo-controlled double-masked trial of 38 patients with blepharitis and MGD, demonstrated (after 12 months of intake), an improvement in meibum production and quality in the omega-3 EFA group over a placebo of olive oil. (37) Other research has shown similar improvements against placebos, (38-40) but a systematic review by Tyagi and colleagues (2014) concluded that there is a wide variability in the methodology amongst studies reported to date, and there is a need for robust clinical trials with well defined and universally accepted inclusion criteria for MGD and outcome measures. (41)

Conclusion

A modern strategy to manage patients out of the vicious cycle of dry eye can include a variety of approaches. Sufficient evidence exists to suggest that it is feasible to reduce inflammation, improve tear film stability and secretion of aqueous and meibum by modifying diet and lifestyle, but it should always be remembered that current nutritional status would affect the ability to benefit from such changes. In the more chronic or troublesome cases a combined approach of lid care, dietary and tear supplementation (and anti-inflammatory therapeutic agents) can be applied, and there will be some patients, such as office workers or contact lens wearers, who might prefer convenient dietary supplementation instead of eye drops or lid care regimes. As the UK diet tends to be deficient in omega-3, so it would seem that supplementation that contains EPA or DHA plus GLA (omega-3 and omega-6 combined) is a balanced combination for relief of dry eye symptoms.

Understanding omega

Omega-3 (alpha-linolenic acid, ALA) comes primarily from oily fish (salmon, mackerel, tuna), as well as flaxseed oil and walnuts. In the body ALA gradually converts to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have anti-inflammatory properties. EPA and DHA can be extracted and purified from fish oils.

Omega-6 (linoleic acid, LA) mostly comes from sunflower and corn oil, as well as nuts and seeds. In the body, LA converts to gamma-linolenic acid (GLA), which has anti-inflammatory properties, but GLA can be converted into arachidonic acid (AA), which tends to be pro-inflammatory if not enough EPA is present. GLA is found in evening primrose oil and borage oil.

FOOTNOTE

Dietary supplements are not a substitute for a healthy, balanced diet. People who are taking any medication, or are pregnant or breastfeeding should seek medical advice before taking dietary supplements.

Professor Christine Purslow PhD, MCOptom, FBCLA, FIACLE

Professor Christine Purslow is an optometrist, educator and researcher, with a specialist interest in the tear film and ocular surface. After several years in academia, most recently as head of optometry at Plymouth University, Christine is now head of medical affairs for Spectrum Thea (the UK subsidiary of Laboratoires Thea, France), alongside her research roles at Cardiff University, and as visiting Professor at Plymouth University.
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Title Annotation:1 CET POINT
Author:Purslow, Christine
Publication:Optometry Today
Date:Nov 28, 2014
Words:2838
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