Dry eye and Omega 3 – essentials about the essentials

by Saj Khan

For more than the last quarter of a century, the awareness of the prevalence and significance of the condition often dismissively referred to as ‘mere’ dry eye has been increasing at an exponential rate.

As a condition that afflicts hundreds of millions of people throughout the world, affects quality of life on a par with angina(1) and increases the risk of anxiety/depression by 50% (2), dry eye disease (DED) is one of the most frequent causes of patient visits to eye care practitioners.

Even before the 1995 NEI/Industry Workshop on Clinical Trials in Dry
Eye, dedicated groups of ophthalmic practitioners and scientists have been attempting to produce a universally agreed definition, classification and management plan for DED. As the collaborations and focus of these groups have evolved, most notably resulting in the publishing of the first and second reports of the Dry Eye Workshop (DEWS 1 & 2) of the Tear Film and Ocular Surface Society (TFOS) in 2007 and 2017 respectively, so too has the evidence base and congruity of approach.
The most recent definition of dry eye from DEWS 2 states “Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage and neurosensory abnormalities play etiological roles”.

If we take a moment not to be put off by the length of the statement, this is less restrictive than earlier definitions but with a more comprehensive acknowledgement of the causal role of factors such as hyperosmolarity and ocular surface inflammation.

In between DEWS 1 and 2, the opening sentence of the report of the 2011 International Workshop on Meibomian Gland Dysfunction(MGD) states “Meibomian gland dysfunction (MGD) may well be the leading cause of dry eye disease throughout the world”, though only tentatively touching on
the association of inflammation as a causative factor., whilst Badouin et al. identify a much stronger association at several points within the vicious circle of dry eye disease (3). The consistent theme above is of inflammation, of various structures and at different stages of the pathophysiological process, being a pivotal root cause in the etiology of dry eye.

This is not new information.

The literature is strewn with a plethora of publications and references, but still today, despite this enhanced knowledge supported by an array of diagnostic tools and guidelines, I am surprised and disappointed on a weekly basis by how few patients with chronic, significant dry eye problems have been made aware of this basic fact. Sadly, most treatment for dry eyes is still advised as a reactive measure rather than being proactive and is focused as a local ocular treatment and not necessarily attempting to address some of the fundamental underlying issues.

Despite the DEWS reports having succinctly refined and provided a clear, systematic, 4 step approach to treatment, the lack of patient education is a failure of the first part of the first step – having always been taught that the easiest way to follow a path is to start at the beginning so you can only follow it in the right direction, this does not bode well – either for patient understanding/compliance, or for appropriate/successful treatment being provided by the practitioner.

In the absence of a direct local trigger such as trauma, inflammation anywhere in the body is fundamentally a systemic process and one that is essentially determined by the balance of essential fatty acids (EFAs) in our system: omega 3 and omega 6.

In the context of MGD and dry eyes, inflammation will cause meibum to become thick and block the meibomian glands. The blocked glands become inflamed. As the blocked glands are not releasing healthy meibum to form the lipid layer of the tears, an evaporative dry eye results in irritation and inflammation of the ocular surface, which in turn also generates increased friction with the inflamed eyelid to propagate the vicious cycle of dry eye disease.

Essential fatty acids are essential in that they are not able to be produced or stored by the body and must therefore be consumed. Though both are needed for the body to function normally, omega 3 has anti-inflammatory properties whilst omega 6 is pro-inflammatory and thus the ratio of these 2 EFAs is crucial to good health – a fact long recognised by our colleagues taking care of patients with cardiovascular, joint, cognitive and skin problems amongst others.

Good sources of omega 3 are oily fish, flaxseed, nuts and dark leafy vegetables. There are different types of omega 3 but the most common are eicosapentaenoic acid(EPA), docosahexaenoic acid(DHA) and alphalinoleic acid(ALA), with EPA and DHA being the most important ones.

Omega 6 sources include vegetable oil, butter, mayonnaise and fast/processed foods, which typically means most people will ingest more omega 6 than omega 3 on a daily basis. The pro-inflammatory effects of omega 6 are important in the healthy functioning of our immune and defence systems, but in excess those same properties become detrimental.

In an ideal scenario, the ratio of omega 3:6 should be close to 1:1. However, with modern western diets these ratios can be found as high as 1:25 and even 1:50. It is therefore important for patients with DED to supplement with high dose, high quality omega 3 supplements in order to restore the more optimal ratio and reduce the undesirable pro-inflammatory effects.

Patients suffering from dry eye and treated with high dose oral omega 3 supplements demonstrate clinical improvements in symtoms, meibum quality, ocular surface staining(4).

However it is important to understand that not all omega 3 supplements are the same. Omega 3 supplements are most commonly found in ethyl-ester form, as this is associated with cheaper production costs, but is recognised as being less bioavailable than the re- esterified triglyceride form which undergo an extra manufacturing step to remove the ethanol molecules from the ethyl-ester form (5,6).

In ethyl-ester form the body relies on pancreatic lipase enzymes to covert it into the triglyceride form to enable absorption – in the absence of this step the re-esterified triglyceride form is more easily absorbed and thus achieves between 3 and 6 fold greater bioavailability, which will typically translate to greater clinical efficacy.

In my own clinical practice, I explain the above and recommend to all patients with clinically significant dry eye that they should commence regular oral re-esterifed omega 3 supplements, with the assumption that they will maintain supplementation, often at a reduced dose once controlled, for life. It is imperative that they understand the need for consistent and regular ingestion and that the effect will take a few weeks to build up gradually. Despite this, it is not uncommon to have patients commence treatment and then stop after a few weeks because they can not feel the benefit – until they stop taking the supplements and notice a more obvious deterioration of the improved symptoms.

As a long term (>25 years) dry eye sufferer myself, re-esterified oral omega 3 supplements, initially PRN Omega Eye and more recently at a lower dose with Optase Omega Vision, have been the foundation of my dry eye control for almost a decade – the consistency allowing me to be more flexible with my lid hygiene and lubrication regimes.

1. Schiffman et al. Ophthalmology. 2003 Jul;110(7):1412-9. Utility assessment among patients with dry eye disease.
   2. Chiang et al. 2013 PLoS One. 2013; 8(12): e83335.
2. 3. Badouin et al. BJO. 2016; 100:300-306. Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of meibomian gland dysfunction
   4. Smith, G. 2011. First Evidence Of Omega-3 EPA/DHA Effect On A Potential Root Cause Of Dry Eye Syndrome Presented At The Cornea Society/EBAA Fall Educational Symposium
   5. Offman et al. Vasc Health Risk Manag. 2013; 9: 563–573.
   Steady-state bioavailability of prescription omega-3 on a low-fat diet is significantly improved with a free fatty acid formulation compared with an ethyl ester formulation: the ECLIPSE II study 6. Dyberg et al. Prostaglandins Leukot Essent Fatty Acids. 2010 Sep;83(3): 137-41. doi: 10.1016/ j.plefa.2010.06.007. Bioavailability of marine n-3 fatty acid formulations.