The Summer 2018 issue of Nutraceuticals Now is now available.
Excerpts of featured articles are available on this website:
In the past, Dry Eye Syndrome (DES) was mainly age-related: a condition in seniors using certain pharmaceuticals such as anti-Parkinson medication, beta-blockers and anti-histamine products. In addition, it was a cardinal symptom in patients with diseases of the tear gland such as Sjøgrens syndrome, as well as subjects with allergic diseases.
Today, DES is far more common. Otherwise healthy individuals carrying contact lenses, computer workers, and people working in a dusty or smoky environment are all affected. Furthermore, the air in air conditioning (AC) supported environments is very dry and this adds to the problem. Modern AC systems are equipped with dust filters, but if these are not changed regularly the AC device will spread the room, or the car, with dust particles. Computer screens may emit electrical charged particles bombarding the conjunctiva of the eye having an opposite charge, thereby working as a magnet to these particles. Modern screens have reduced this negative effect, but long days with computers still represents a problem. Concentrating on the screen reduce the blinking re ex, thereby reducing the smearing effect of the tear fluid, which could increase DES symptoms. Corrective eye surgery in which a gap of the corneal surface is raised and a thin layer of underlying tissue is removed using a laser (LASIK) lists DES, often passing, as one of the risks by having the procedure. The most common complaint amongst those affected is having a scratchy or foreign body sensation. Redness, pain, itching, inability to produce tears, light sensitivity, and blurred vision with difficulty driving after dark are all common symptoms. The symptoms are located mainly to the pain sensitive cornea (Fig. 1).
Fig. 1. Cornea is the light transparent frontal part of the eye. Conjunctiva is the mucosal layer covering the inside of the eyelids (palpebral conjunctiva) and the anterior part of the eye bulb (bulbar conjunctiva) connecting with the cornea. Conjunctiva is composed of a highly vascularized epithelium with a complex nerve supply. The tear producing lacrimal glands are located on both sides of the eye socket.
Previously, artificial tear products were recommended to relieve symptoms since people with DES have reduced tear production. Tears are produced in the lacrimal glands, and the fluid is a complex composition of water, salts, proteins and lipids. Cornea, having no blood vessels, is supplied with nutrients contained within the tear fluid.
Recent animal experiments have demonstrated that DES is not exclusively a disease located to the cornea since inflammatory cells and immunological chemical mediators were found in the tear fluid. Since cornea does not contain tissue engaged in an inflammatory process, the lacrimal gland and the conjunctiva have to participate in the syndrome even though symptoms relate to cornea. This exploration opened up for a novel treatment of DES providing systemic anti-inflammatory treatment leaving the modality of solely artificial tears behind.
He Jiucheng and Haydee Bazan were the first to suggest that DES was a multifactorial condition affecting the total surface of the eye and inducing an inflammatory response1. Facing a trauma or infection, tissue respond with production of endogenous anti-inflammatory compounds such as the novel compounds Resolvins belonging to the group of specialized pro-resolving mediators (SPM). These are mainly derived from marine Omega-3 fatty acids enriched in our cells, provided we have a regular intake of fish. Artificial Resolvins were given in an experimental setting where DES animals were treated topically 4 times per day for one week2. Tear production was promoted, corneal cell integrity was corrected, and inflammatory mediators were reduced.
This important experiment paved the way for a new type of DES treatment providing the starting material for Resolvin production in the conjunctiva and lacrimal gland namely marine Omega-3 fatty acids.
Several controlled clinical studies have been published where these fatty acids have been given in a placebo- controlled design.
Rahul Bhargava and colleagues3 included 264 DES subjects given 1 g daily of marine Omega-3 fatty acids, mainly eicosapentaenoic acid (EPA), and compared effects on symptoms, tear production and corneal cell integrity. A large control group of 254 individuals were given matching placebo. After three months, there was a significant reduction in symptom score in the Omega-3 group along with improvement in tear production and corneal cell integrity.
In a study by Kangari H and colleagues4, 64 subjects with DES were divided in an intervention group given the same dose of Omega-3 fatty acids as in the previous study, and a placebo-controlled group. This study also demonstrated that Omega-3 fatty acids improved DES symptoms, with an increased tear secretion.
Kawatita K et al5 included 27 DES patients in a study providing half of the group with a product containing 1.3 g of EPA and 0.5 g of docosahexaenoic acid (DHA) daily for 12 weeks. Symptoms were significantly reduced in the intervention group.
In yet another study by Bhargava R and Kumar P6 496 contact lens carriers with DES were randomly allocated to treatment with marine Omega-3 fatty acids (0.6 g daily), or placebo for six months. The study demonstrated a significant improvement in dry eye symptoms and an increase in tear secretion in the Omega-3 treated group.
In another study by Bhargava R and colleagues7, including 428 computer workers with DES, half the group were given the same dose of Omega-3 fatty acids as in study 6. The rest were provided with matching placebo capsules and followed for three months. There was a significant improvement in symptoms followed by increased tear production in the active treatment group.
In a meta-analysis of published studies using a randomized, placebo-controlled design, Liu A and Yi J included a total of 790 participants in seven independent studies published between 2007 and 20138. The authors concluded that, based on the experience from these studies, Omega-3 fatty acids seemed to offer an effective therapy for DES.
In conclusion, the finding of inflammatory cells and chemical mediators of the immune system in tear fluid of animals with DES opened up for a new view on the disease. Even if symptoms are related to the cornea, inflammatory cells had to have a different origin. The cornea is deprived of blood vessels, while the conjunctiva and lacrimal gland supporting cornea with fluid and nutrients are tissues responding to trauma causing DES with production of immunologic mediators like Resolvins. Resolvins, in turn, are derived from Omega-3 fatty acids. Several controlled clinical studies have demonstrated positive effects of Omega-3 products in a dose from at least 0.6 g mainly containing EPA. Our modern environment dispose to DES from particles and dry air by AC installations in cars, homes and where we work, from contact lenses, computer work, air pollution and cigarette smoking. DES is also a registered risk in those undergoing corrective eye surgery using a laser (LASIK) the first 6 months or so following the procedure.
A dose of about 1 g daily of a high-EPA product once daily is recommended.
From a commercial point of view, the market for dietary supplements helping people cope with DES is ever growing due to the very common triggers listed above. Those affected have formerly only been given the option of eye drops to help with the problem, which, as the more recent research cited in this article points out, is not an optimal treatment. In addition, eye drops containing preservatives have also been reported to lead to allergic reactions. Omega-3 potentially offers a relief to those suffering from DES. Epax, dating back to 1838 and now one of the world’s leading suppliers of premium quality, highly concentrated Omega-3, can supply customized EPA:DHA ratios to target the root cause for DES, rather than just managing the symptoms. Epax products are sustainably sourced, and manufactured at a FDA-inspected facility.
Morten Bryhn MD, PhD