Managing ocular surface disease in contact lens patients poses additional challenges for the eye care practitioner. For example, we must also factor in lens-solution compatibility and preservative-related reactions. An often overlooked, but potentially beneficial, means of managing these patients is through nutritional supplements.

While the use of supplements is frequently mentioned in anecdotal reports, recent studies have provided evidence-based literature to help guide us in the use of essential fatty acids in the management of ocular surface disease. While there are still some unanswered questions and larger, additional studies are needed, this column will offer an understanding of the research to date.

Fatty Acids
Essential fatty acids (EFAs) are polyunsaturated fats with multiple double bonds in the carbon chain. These EFAs are necessary for development, for certain biological processes and cannot be synthesized by the body. Linoleic acid (LA) and alpha-linoleic acid (ALA) are the shortest chain EFAs and once in the liver are converted to longer-chain, polyunsaturated fatty acids.

Omega-3 (n-3) and omega-6 (n-6) are fatty acids and are precursors for the production of eicosanoids—prostaglandins, thromboxanes and leukotrienes—that regulate inflammatory processes. Some of these compounds possess proinflammatory effects and others manifest as anti-inflammatory.1,2

Examples of n-3 fatty acids are ALA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Food sources high in n-3s include cold water, dark fish (e.g. salmon, sardines, tuna, mackerel and herring), flaxseed oil and walnuts.1 These fatty acids tend to be anti-inflammatory.
Some n-6 fatty acids are healthy while others are not. Examples of n-6 fatty acids are LA, gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA). Sources of n-6 include soybean oil, palm oil, canola oil, sunflower oil, poultry, nuts, eggs and cereals.1,2
Although it may seem counterintuitive, the use of certain n-6 compounds appear to have anti-inflammatory effects. In particular, GLA is converted to DGLA—which increases the synthesis of 1-series prostaglandins (e.g. PGE1) that have a negative feedback role in inflammation and also minimizes the production of PGE2 and 4-series leukotrienes, which are inflammatory.3 Consumption of evening primrose oil or borage oil are good sources of LA and GLA, which are “good” n-6s.

EPA (n-3) and AA (n-6) compete for cyclooxygenase and 5-lipoxygenase enzymes. The anti-inflammatory effects of EPA are due to the synthesis of PGE3 and leukotriene B5. These prevent the conversion of AA to inflammatory mediators such as PGE2 and leukotriene B4.4 Therefore, a diet high in EPA can reduce the production of AA by competitive enzyme inhibition. Altering the consumption of fatty acids either by diet or with supplementation can alter the ratio and the inflammatory effects.

Consumption Guidelines
The current thinking is that the dietary intake ratio of n-6 to n-3 should be between 1:1 and 4:1. The American diet is reported to be as high as 15:1 to 30:1, which may correlate with the high rates of heart disease, autoimmune conditions and cancers prevalent in Western populations.1,2
The benefits of a healthy n-6:n-3 ratio relative to ocular surface disease are multifactorial—these fatty acids appear to enhance the lipid layer by decreasing evaporation, increasing tear production and reducing the inflammatory component of dry eye.

The Research
Several studies have evaluated n-3s, n-6s or a combination of these. GLA and LA (both n-6s) have been shown to improve symptoms in conditions associated with inflammation, such as rheumatoid arthritis and dry eye.3,5 In a study conducted by Karolien H. Kokke, MSc, MCOptom, of Sussex Eye Hospital, United Kingdom, and colleagues, the use of evening primrose oil (a source of n-6s) alleviated symptoms and improved comfort in contact lens associated dry eye. An increase in tear production was also noted.3

A study by Antonio Pinna, MD, of the Institute of Ophthalmology at the University of Sassari, Italy, and colleagues showed that increasing n-6, along with lid hygiene, improved symptoms and inflammation associated with meibomian gland dysfunction. The authors suggested that the EFAs helped normalize the melting point of the meibomian gland secretions.6

Biljana Miljanovíc, MD, MPH, MSc, has reported that when n-6 to n-3 ratio exceeds 15:1, the likelihood of dry eye symptoms increases.3 Data from the Women’s Health Study, which surveyed 32,000 women, noted that both low intake of n-3 and high n-6:n-3 ratio were associated with an increased risk of dry eye.3

A study by Mitchell A. Jackson, MD, director of Jacksoneye in Lake Villa, Ill., and colleagues showed that using Tears Again Hydrate (OcuSoft) as a n-3 and n-6 prescription supplement improved tear break-up time and patient symptoms.7 Using a dietary supplement of n-3, Jadwiga Cristina Wojtowicz, MD, and colleagues reported no change in meibum composition, but noted that tear production did increase.8

A multi-center study by Françoise Bignole-Baudouin, MD, PhD, and colleagues at the Institut de La Vision in Paris, demonstrated that supplementing with EFAs reduced the HLA-DR conjunctival inflammatory marker.9 While a few studies did not find any significant improvement in clinical findings with the addition of nutritional supplements, most published studies demonstrate improvements subjectively and/or objectively.1-3,9,10

On the Shelf
There are hundreds of commercially available EFA nutritional supplements on the market today. Most are not FDA-regulated, so selecting an appropriate supplement can be challenging. Flaxseed is comprised of approximately 50% ALA, but only a very small percentage is transformed to an anti-inflammatory compound. Fish oil capsules usually contain approximately 300mg of EPA/DHA per 1,000mg capsule but this varies greatly; products have also been found to over-report the amount of EPA/DHA. Prescription-only Lovaza (GlaxoSmithKline), which is labeled for the treatment of severe hypertriglyceridemia (≥ 500mg/dL), has 465mg of EPA and 375mg of DHA per 1,000mg capsule.

All of the above supplements are merely a source of n-3. From the limited studies and understanding of the importance of certain n-6s, a supplement that provides both n-3 and n-6 might be the best option to recommend to patients to manage dry eye symptoms. There are many of these products available, but some examples include Tears Again Hydrate, TheraTears Nutrition (Advanced Vision Research), HydroEye (ScienceBased Health), BioTears (Biosyntrx) and Dry Eye Relief (VisiVite). Side effects are minimal but some patients may complain of some stomach upset and belching. A consultation with a patient’s prescribing physician is warranted prior to recommending these supplements to patients on blood thinners.

Taking a capsule or two daily to manage dry eye symptoms is an often very effective and a convenient management strategy for patients, especially those wearing contact lenses. 

1. Rand AL, Asbell PA. Current opinion in ophthalmology nutrition supplements for dry eye syndrome. Curr Opin Ophthalmol. 2011 Jul;22(4):279-82.
2. Roncone M, Bartlett H, Eperjesi F. Essential fatty acids in dry eye: a review. Cont Lens Anterior Eye. 2010 Apr;33(2):49-54.
3. Kokke KH, Morris JA, Lawrenson JG. Oral omega-6 essential fatty acid treatment in contact lens associated dry eye. Cont Lens Anterior Eye. 2008 Jun;31(3):141-6.
4. Cortina MS, Bazan H. Docosahexaenoic acid, protectins and dry eye. Curr Opin Clin Nutr Metab Care. 2011 Mar;14(2):132-7.
5. Belch JJ, Hill A. Evening primrose oil and borage oil in rheumatologic conditions. Am J Nutr. 2000 Jan;71(1 Suppl):352S-6S.
6. Pinna A, Piccinini P, Carta F. Effect of oral linolenic and gamma-linolenic acid on meibomian gland dysfunction. Cornea. 2007 Apr;26(3):260-4.
7. Jackson MA, Burrell K, Gaddie IB, et al. Efficacy of a new prescription-only medical food supplement in alleviating signs and symptoms of dry eye, with or without concomitant cyclosporine A. Clin Ophthal. 2011;5:1201-6.
8. Wojtowicz JC, Butovich I, Uchiyama E, et al. Pilot, prospective, randomized, double-masked placebo-controlled clinical trial of an omega-3 supplement for dry eye. Cornea. 2011 Mar;30(3):308-14.
9. Brignole-Baudouin F, Baudouin C, Aragona P, et al. A multicentre, double-masked, randomized, controlled trial assessing the effect of oral supplementation of omega-3 and omega-6 fatty acids on a conjunctival inflammatory marker in dry eye patients. Acta Ophthalmol. 2011 Nov;89(7):e591-7.
10. Oxholm P, Manthorpe R, Prause JU, et al. Patients with primary Sjögren’s syndrome treated for two months with evening primrose oil. Scand J Rheumatol. 1986;15(2):103-8.