Dry eye is one of the most common ophthalmic disorders. We are all familiar with the presenting signs and symptoms, and now that we have many tests to aid in diagnosis and management. Therefore, it is relatively easy to detect individuals with dry eye, but it is often difficult and frustrating to treat these patients.
The diagnosis of dry eye is made by a careful history and slit lamp exam of the ocular surface. Patient questionnaires such as OSDI and SPEED can be helpful and provide a simple quantitative value for the extent of disease. Inspection of the eyelids, tear film, conjunctiva, and cornea is mandatory, and vital dyes are an essential part of the examination.
Newer diagnostic aids such as the Tear Lab Osmolarity System which quantitates tear osmalarity level, InflammaDry which measures MMP-9 levels, Oculus Keratograph and LipiView which are tear film analysis devices that evaluate tear lipid layer, tear meniscus height, and blink pattern, are becoming more popular. These tests not only quantify dry eye parameters but also allow the physician to better educate patients with tangible numbers and images that demonstrate their disease.
The DEWS report serves as an excellent guideline for dry eye management according to disease severity. Treatment options for dry eye disease include lubrication with artificial tears, topical cyclosporine (Restasis), occlusion of the lacrimal puncta, topical steroids, and treating associated pathology such as eyelid abnormalities, systemic diseases, ocular surface inflammation, etc. In fact, we now recognize that dry eye disease has an inflammatory etiology, so it is not surprising that Meibomian gland dysfunction is the most prevalent form of dry eye disease. A recent multi-center study presented at the 2015 ASCRS annual meeting showed the beneficial role of oral fish oil (omega-3s) supplementation in the treatment of dry eye.
Omega-3s are essential fatty acids, which means that they cannot be made by the body but instead must be consumed in our diet. Specifically, they are eicosapentaenoic acid (EPA) and docosahaxenoic acid (DHA), and they are anti-inflammatory agents that are necessary to balance the pro-inflammatory omega-6 fatty acids such as linoleic acid and arachidonic acid.
Ideally, the balance of omega-6s to omega-3s is 1:1 and preferably less than 4:1. However, the average American citizen consumes a diet high in saturated fats resulting in a fatty acid imbalance of up to 30:1. Such an unhealthy balance has been linked to numerous inflammatory conditions and disease states such as cardiovascular disease and cancer. Many studies have demonstrated the health benefits of omega-3 fatty acids including cardio-protection (omega-3 index (serum level in RBCs) > 8%), lower risk of dementia such as Alzheimer’s Disease, relief of joint pain, and efficacy in dry eye disease. They may also have beneficial effects for ADHD, asthma, autoimmune disease, cancer, depression, periodontitis, and macular degeneration (AREDS2 used a sub-therapeutic dose).
Although omega-3 fatty acids offer a multitude of therapeutic effects, not all available over-the-counter (OTC) omega-3s are created equal. Therefore it is important to understand the differences between the two forms of omega-3s when counseling patients about these products.
Fish oil omega-3s are triglycerides (fatty acids with a glycerol backbone) in nature but are chemically altered during purification to an ethyl ester (EE) form (i.e., a fatty acid with an ethyl ester backbone). OTC products are most commonly sold in the EE form, but some companies convert the omega-3s back to the triglyceride form (called re-esterified TG (rTG)) with a glycerol backbone. The term re-esterified is a confusing designation. It does not mean that this is an ester form, but rather it refers to the fact that the type of bond between the fatty acids and the glycerol backbone is an ester bond. The differences between the EE and rTG forms of fish oil supplements can be summarized as follows:
EE: Created during processing to remove contaminants, poorly absorbed, more side effects (i.e., fish burps, GI distress, etc.), less stable, and cheaper. Alpha-tocopherol (synthetic vitamin E) is a preservative added to EE formulations to stabilize the product and prevent spoiling, but it causes increased bleeding. The majority of OTC fish oil products are ethyl ester formulations.
rTG: A more natural form that is better absorbed in GI tract with no side effects and more stability, but a higher cost because it must be resynthesized from ethyl ester form. Physician Recommended Nutriceuticals (PRN; validated in multicenter US study for dry eye) and Nordic Naturals are examples of fish oil supplements that are formulated as re-esterified triglycerides.
There are clearly major differences between the EE and rTG omega-3 supplements. A recommended dosage of 2000-3000 mg of the triglyceride form must be ingested to achieve a therapeutic level of omega-3 fatty acids. However, most patients have a suboptimal level because they are taking the EE form, which is poorly absorbed and often difficult to tolerate owing to the side effects which can lead to a lower compliance rate.
A thorough understanding of omega-3 fatty acids is important for all physicians so we can properly educate our patients and give them the best advice regarding effective supplement therapy. In my practice, I have found rTG omega-3s to be quite effective and now recommend them to all my dry eye patients, particularly for those undergoing cataract and refractive surgical procedures.