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Sep 30, 2023

Dry eye disease and nutrition: are we what we eat?

At the completion of this article, the reader should be able to improve their

At the completion of this article, the reader should be able to improve their management of dry eye disease, including:

• Understand the impact of excipients, additives and non-nutritional components on ocular health• Provide informed recommendations to patients with regards to their nutrition and their ocular surface health• Understand the importance of the ratio of omega 3s to omega 6s• Understand the role of the gut microbiome and where the research currently stands

Tear Film and Ocular Surface Society (TFOS) has published a report into the consequences of lifestyle choices on the ocular surface, including the impact of nutrition. A/Prof Maria Markoulli, chair of the Nutrition Subcommittee, discusses the latest findings.

Maria MarkoulliPhD MOptom GradCertOcTher FBCLA FAAOAssociate Professor | Director of Learning & Teaching |Academic lead UNSW Dry Eye clinic |School of Optometry and Vision ScienceDeputy Editor | Clinical and Experimental OptometryBoard Member | The Optical FoundationTFOS Ambassador

Impact of diet on dry eye disease?

We do not yet know what the optimal dietary intake needs to be to prevent and manage dry eye disease.

Diet can be looked at in terms of macronutrients (carbohydrates, lipids [also called ‘fats’] and proteins), micronutrients (vitamins and minerals) and hydration. In terms of macronutrients, there is some evidence that polyunsaturated fatty acids can help resolve dry eye-related inflammation.

Fats

The current hypothesis is that omega 3 in the diet might reduce the risk of dry eye disease and relieve its symptoms because of its known anti-inflammatory properties.

The ratio of omega 6 to 3 matters when it comes to our health. Omega 6 is found in food like corn, meat, poultry and eggs. Common sources of omega 3 are oily fish such as salmon, nuts and seeds. While modern Western diets typically boast an omega 6 to omega 3 ratio around 10 to 1, (sometimes as high as 30 to 1) the optimal ratio for health is less than 4 to 1.

In the Women's Health Study of more than 32,000 women older than 45 years, a higher omega 6/ omega 3 ratio was associated with a significantly increased risk of dry eye disease; those consuming higher levels of omega 6 had a 2.5 times higher risk of developing dry eye than those who consumed the recommended ratio of less than 4 to 1.1

Additionally, a 30% reduction in dry eye risk was found with each additional gram of omega 3 polyunsaturated fatty acids consumed each day.1

There is limited evidence for the beneficial effects of extra virgin olive oil and primrose oil2 and there is only indirect evidence for other vegetable oils, sugars3 and artificial sweeteners.4

Micronutrients

With regards to micronutrients, the major vitamins playing a role in ocular surface diseases include vitamin A, B12, C and D. Deficiency of vitamin A is the most frequent form of malnutrition that contributes to ocular disease.5,6 Of the minerals, the levels of selenium in tears have been found to be decreased in a dry eye model.7 One study reported a relationship between low levels of tear lactoferrin and the development of dry eye disease.8

Hydration

Based on the current limited studies, increased water intake has not been tied to improved dry eye or ocular surface outcomes. Increasing hydration has been associated with health benefits, such as increased skin hydration. With regards to the ocular surface, plasma osmolality and tear osmolarity have been shown to be strongly correlated. 9,10 No change in other clinical parameters has been reported.11,12 A population-based study investigating the association between both water intake and 24 hour urine volume found that neither were associated with a protective risk of dry eye.13

What do we know about excipients, additives and non-nutritional components?

Endocrine-disrupting chemicals

Endocrine-disrupting chemicals (EDCs) are substances in the environment (air, soil or water supply); food sources; personal care products and manufactured products that interfere with the normal function of the body's endocrine system. EDCs are compounds that can bind to the hormone receptors of cells to activate – or block – the action of hormones, including sex hormones.

The main source of EDCs for humans is from ingestion or leaching from food containers or contamination during manufacturing or processing of foods. A systematic review concluded that there is growing evidence of these chemicals are changing the diversity of the gut microbiome.14

Further studies on the role of EDCs in ocular surface disease are clearly needed including any impact on the ocular microbiome.

For example, it has been found that Bisphenol A (BPA) – one of the best known EDCs and the chemical used in the production of polycarbonate plastics such as eyewear, water bottles and epoxy coatings of some metal food cans and bottle tops – has the ability to bind to estrogen and has been shown to increase interferon-y and interleukin-17 in vitro in dendritic cells of patients with primary Sjögrens syndrome.15

Parabens

Parabens are a group of chemicals found in shampoos, makeup, toothpaste and shaving gels as well as food products like mayonnaise, salad dressings, and soft drinks. A 2020 study found significant positive correlations between dry eye signs and several parabens in the urine.16

Mercury

Mercury poisoning most commonly occurs via consumption of mercury-contaminated seafood. Increased tear osmolarity, tear cytokine tear levels and decreased subbasal corneal nerve morphology have been reported,17 and blood concentrations of mercury have been linked to dry eye symptoms.18,19

Alcohol

With regards to alcohol, two small studies have investigated the effect of a single event of alcohol intake, and found increased tear osmolarity, shortened tear breakup time and more ocular pain in the hours after alcohol consumption.20,21 A meta-analysis that included 10 studies found that alcohol was weakly associated with dry eye disease.22 There was no increased risk of dry eye seen in heavy drinkers.22

Food additives

There has not yet been any published research related to the possible effects of food additives nanoparticles, emulsifiers and flavour enhancers, on the ocular surface even though these compounds have been increasingly associated with various negative health effects in the human body.

What impact do different diets have?

The TFOS report explored the Western diet, Mediterranean diet, African diet and Asian diet. Of these, only the Mediterranean diet was found to have any direct evidence from human studies linked to ocular surface impact. The Mediterranean diet has been reported to be useful in chronic inflammatory diseases due to its anti-inflammatory properties. Given these properties, it might be expected to have benefits in treating dry eye disease. To that end, a higher adherence to a Mediterranean diet has been associated with a lower likelihood of developing primary Sjögrens syndrome.23 Another study randomised participants with Sjögrens to either a Mediterranean diet supplemented with extra virgin olive oil and nuts; or a hypocaloric Mediterranean diet and physical activity.24 In both groups, both the signs and symptoms of dry eye disease improved after six months, although more so in the group with exercise.24

When a systematic review within the report looked at the role of intentional food restriction such as occurs in religious fasting, bariatric surgery, short-term fasting, riboflavin depletion diet, anorexia nervosa and celiac disease, none of the studies were judged to be of high quality, most commonly due to the lack of masking and not reporting sample size calculations. ‘Mixed results’ were reported in relation to the effects of religious fasting, low certainty evidence for bariatric surgery and no clinical meaningful difference in anorexia nervosa.

Can supplements help with dry eye disease?

Increased Schirmer scores and increased tear meniscus has been reported after caffeine ingestion.11 In two large population-based studies, caffeine use was associated with a protective effect on dry eye but this protective effect was not seen after correction for dry eye associated comorbidities, age and sex.25,26

Manuka Honey has been studied in and around the eye but less so as a dietary supplement. One double-masked randomised controlled trial found improved tear break-up time and Schirmer test scores;27 two studies found conflicting data on the impact of honey on allergic symptoms.28,29

Curcumin (the substance responsible for the golden colour in turmeric) has been found to inhibit oxidative stress, angiogenesis and inflammation. In humans, a curcumin combination taken for eight weeks improved signs and symptoms of dry eye disease.30

There are multiple reports of vitamin A improving dry eye symptoms.31

Although a deficiency in selenium has been associated with thyroid eye disease,32 a meta-analysis of two trials evaluating the efficacy of selenium supplementation for six to nine months in patients with Graves’ ophthalmopathy found no statistically significant difference in thyroid stimulating hormone receptor antibodies compared to placebo.33

Potentially the most studied dietary supplements relating to the ocular surface are omega 3 polyunsaturated fatty acids. When it comes to omega 3 supplements, results from clinical trials have had mixed results, often due to differences in study design.

A meta-analysis that investigated omega 3 versus placebo and included 17 randomised controlled trials with greater than 3,000 patients found that omega 3 supplementation decreased dry eye symptoms and signs.34

We need future research to more clearly define who goes into these studies, to establish a set of core outcome measures, and to determine the optimal dose, composition and duration of supplementation necessary.

The impact of the gut microbiome and its modulation

The gut microbiome seems to be ‘in vogue’. It has been linked to a range of systemic diseases, including autoimmune disease and depression. Its link to dry eye disease stems from the role it plays in the regulation of low-grade chronic inflammation.

Ecological shifts within the gut microbiome can induce imbalance or ‘dysbiosis’, which is associated with chronic disease. In dry eye disease, severe gut dysbiosis has been found to be significantly more prevalent in patients with Sjögren's syndrome, compared to healthy controls.35 An obvious path to follow here is to explore whether modulation of the gut microbiome plays a role in treating dry eye disease.

Prebiotics boost the function of probiotics and other good bacteria, while probiotics include beneficial bacteria and can be obtained from fermented foods or commercial supplements. When a combination of prebiotics and probiotics was given to a group of people with dry eye disease for one month, when compared to a control group, the pro/prebiotic group was found to have an improvement in both the signs and symptoms of dry eye disease.36

In another double masked randomised controlled trial, 41 participants with dry eye were randomised to receive pro and prebiotics OR placebo.37 After four months, the average comfort score of the treatment group was significantly better compared to that of the controls.37 The field of modulating the gut microbiome as an intervention to treat dry eye disease is relatively in its infancy. More comprehensive investigations are needed on the proper dosage, duration, and formulation of these supplements.

Does systemic disease as a result of diet also impact the ocular surface?

Many systemic disorders are affected by diet and nutrition. Moreover, systemic disorders may themselves further affect the body's uptake, processing and distribution of nutrients.

Obesity has been linked to floppy eyelid syndrome, blepharoptosis and dry eye disease.38 Dyslipidaemia and hypertension have been similarly associated with dry eye disease.38 Dyslipidaemia and hypertension have been similarly associated with dry eye disease,39 with two systematic reviews highlighting a positive correlation between dyslipidaemia and MGD.40 Metabolic syndrome has been reported to be associated with an increase in osmolarity of the tear film and symptoms, with a decrease in Schirmer and tear break up time, with similar results reported for prediabetes and diabetes,41 along with a decrease in corneal nerves and sensitivity.42

What do I tell my patients?

Good nutrition is clearly pivotal to good health. There is significant evidence that good nutrition also impacts the ocular surface. How exactly nutrition relates to each aspect of ocular surface health is, however, in its relative infancy. We as eyecare professionals need to consider the evidence prior to providing nutritional recommendations to patients with regards to their ocular surface health.

View the full report: Markoulli, M., Ahmad, S., Arcot, J., Arita, R., Benitez-del-Castillo, J., Caffery, B., Downie, L. E., Edwards, K., Flanagan, J., Labetoulle, M., Misra, S., Mrugacz, M., Singh, S., Sheppard, J., Vehof, J., Versura, P., Willcox, M. D. P., Ziemanski, J., & Wolffsohn, J. S. (2023). TFOS Lifestyle: Impact of nutrition on the ocular surface. Ocul Surf, (in press).

More reading

Dry eye – a multifactorial approach to a multifactorial disease

References

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