HydroEye®

• Research Summaries - HydroEye

• HydroEye Monograph

Omega Fatty Acids: GLA (235 mg) from Black Currant Seed Oil, EPA (100 mg) and DHA (70 mg) from Fish Oil
GLA, a unique and specialized omega-6 fatty acid from black currant seed oil, is found only in ultra trace amounts in the diet. GLA can be converted to the anti-inflammatory prostaglandin, PGE1, which supports normal tear secretion. Clinical studies report that GLA reduces symptoms and calms inflammation in those with dry eye, improves symptoms and increases tear production in people undergoing corrective laser procedures, and improves contact lens comfort. It also reduces symptoms and increases anti-inflammatory prostaglandin levels in those with Sjögren's syndrome.

Black currant seed oil also contributes alpha linolenic acid, an important omega-3 fatty acid. A controlled study in healthy older individuals found that black currant seed oil decreased production of the pro-inflammatory prostaglandin, PGE2, and improved immune function compared to a placebo.

Fish oil is a concentrated source of the omega-3 fats EPA and DHA. Higher dietary intake of EPA and DHA may reduce the risk of dry eye, in addition to providing well established cardiovascular benefits. Combining fish oil EPA and DHA with GLA from black currant seed oil in balanced amounts helps block the formation of inflammatory prostaglandins. HydroEye features highest quality USP-verified fish oil from the purest sources.

Vitamin C (240 mg)
Vitamin C is the most abundant water-soluble antioxidant in tear fluid. It acts to neutralize free radicals and helps recharge the antioxidant vitamin E. Biomarkers of oxidative damage are higher in the tear fluid of dry eye patients compared to controls. Levels of vitamin C are also known to drop significantly in the tears of people undergoing laser surgery - procedures known to generate free radical activity. In addition to its free radical fighting role, Vitamin C may also stimulate the formation of less inflammatory prostaglandins from GLA metabolism.

Other Essential Nutrients
HydroEye delivers Vitamin A, an essential nutrient for the health of the epithelial cells of the eye’s cornea and conjunctiva. Vitamin A is also required for the manufacture of mucin, the primary component of the mucous or innermost layer of the tear film. HydroEye contributes mucin, which is secreted by goblet and epithelial cells of the conjunctiva to protect, lubricate and ensure even distribution of tear fluid. Loss of goblet cells has been associated with chronic inflammation of the ocular surface in tear deficient dry eye.

Dietary shortfalls of magnesium and vitamin B6 are not uncommon, especially among women and older individuals (groups in which dry eye commonly occurs). HydroEye includes these nutrients, which are important cofactors for the conversion of linoleic acid from black currant seed oil into GLA. One of the critical catalysts for this conversion is an enzyme whose activity declines with nutrient deficiencies, as well as with age, certain diseases, increased stress hormones and excessive intakes of saturated fats.

1. Goto E, et al. Impaired functional visual acuity of dry eye patients. Am J Ophthalmol 133: 181-186, 2002.
2. Stern ME, et al. The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. Cornea 17: 584-589, 1998.
3. Ang RT, et al. Dry eye after refractive surgery. Curr Opin Ophthalmol 2: 318-322, 2001.
4. Azzarolo AM, et al. Androgen support of lacrimal gland function. Endocrine 6: 39-45, 1997.
5. Baudouin C. Dry eye: an unexpected inflammatory disease. Arch Soc Esp Oftalmol 76: 205-206, 2001.
6. Pflugfelder SC, et al. Diagnosis & management of dry eye: A 25-year review. Cornea 19: 644-649, 2000.
7. Solomon A, et al. Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry eye disease. Invest Ophthalmol Vis Sci 42: 2283-2292, 2001.
8. Zuier RB, et al. Gamma-linolenic acid treatment of rheumatoid arthritis: A randomized, placebo-controlled trial. Arthritis Rheum 39: 1808-1817, 1996.
9. Barabino S, et al. Systemic linoleic and gamma-linolenic acid therapy in dry-eye syndrome with inflammatory component. Cornea 22: 97–101, 2003.
10. Macri A, et al. Effect of linoleic acid and gamma-linolenic acid on tear production, tear clearance and on the ocular surface after photorefractive keratectomy. Graefes Arch Clin Exp Ophthalmol 241: 561-6, 2003.
11. Kokke KH et al. Oral omega-6 essential fatty acid treatment in contact lens associated dry eye. Contact Lens Anterior Eye 31:141-6, 2008.
12. Aragona P, et al. Systemic omega-6 essential fatty acid treatment and PGE1 tear content in Sjogren’s syndrome patients. Invest Ophthalmol Vis Sci 46: 4474-4479, 2005.
13. Wu D, et al. Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects. Am J Clin Nutr 70: 536-543, 1999.
14. Miljanovic B, et al. Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women. Am J Clin Nutr 82: 887-93, 2005.
15. Barham JB, et al. Addition of EPA to GLA-supplemented diets prevents serum arachidonic acid accumulation in humans. J Nutr 130: 1925-31, 2000.
16. Augustin AJ, et al. Oxidative reactions in the tear fluid of patients suffering from dry eye. Graefes Arch Clinc Exp Ophthalmol 233: 694-698, 1995.
    
17. Bilgihan A, et al. Ascorbic acid levels in human tears after photoreactive keratectomy (PRK), transepithelial photoreactive keratectomy, and laser in situ keratomileusis (LASIK). J Cataract Refract Surg 27: 585-588, 2001.
18. Horrobin DF, et al. The regulation of prostaglandin E1 formation: A candidate for one of the fundamental mechanisms involved in the action of vitamin C. Med Hypotheses 5: 849-858, 1979.
19. Tei M, et al. Vitamin A deficiency alters the expression of mucin genes by the rat ocular surface epithelium. Invest Ophthalmol Vis Sci 4: 82-88, 2000.
20. Kunert KS, et al. Goblet cell numbers and epithelial proliferation in the conjunctiva of patients with dry eye syndrome treated with cyclosporine. Arch Ophthalmol 120: 330-337, 2002.
    
21. Bordoni A, et al. Dual influence of aging and vitamin B6 deficiency on delta-six desaturation of essential fatty acids in rat liver microsomes. Prot Leukot Ess Fatty Acids 58: 417-420 1998.

In the News: Omega-3s, Antioxidants and GLA
Omega-3s, Zinc & "C" May Ease Asthma
Results of new research suggest that a combination of fish oil, zinc and vitamin C can improve the symptoms of bronchial asthma in children (1). Asthma, which affects nearly 20 million Americans, is on the rise according to the American Lung Association.
In this double-blind study, 60 asthmatic children were supplemented with 300 mg of EPA and DHA, 15 mg of zinc, 200 mg of ascorbic acid, a combination of all the nutrients or a placebo for 6 week periods. Lung function was measured, as were markers of inflammation. Symptoms such as wheezing, shortness of breath and the use of rescue inhalers were measured in a standardized test.
The researchers found significant improvement in all the tests when the nutrients were given one at a time. However all three nutrients combined produced the best results.
Omega-3s & Better Blood Pressure in Dieters
One of the many benefits of weight loss is often blood pressure reduction, and results of a recent study suggest that the omega-3s can result in even better reductions - at least in those who have low levels of the omega-3 DHA stored in their cell membranes (2). Low levels of cellular omega-3 are believed to reflect infrequent intake of these important fatty acids.
All of the 324 overweight study participants, aged 20-40, were put on weight loss diets and divided into 4 different groups. One group ate salmon 3 times weekly, while another consumed cod, which is lower in omega-3 content. The third group was given supplements providing about 495 mg of EPA and DHA daily, while the forth group was assigned to a placebo and ate no seafood.
All of the study subjects lost weight - a little over 11 pounds on average. Blood pressure also went down overall, but reductions were greater in those eating salmon or receiving the daily omega-3 supplement compared to people in the cod-consuming group and in placebo-takers who had low stores of the omega-3 to begin with. These observations are in line with a number of other study findings that indicate blood pressure reductions with greater EPA and DHA intake.
GLA Makes Contact Wear More Comfortable
Contact lens wearers commonly experience a feeling of dryness in their eyes. As a result, many people wear their lenses less often or discontinue their use altogether. A recent double-blind, placebo-controlled study examined the effects of 300 mg of supplemental GLA daily in 76 women with contact lens-related dry eye (3). The participants all wore soft contact lens.
The women in the GLA group experienced significant improvement in the sensation of dryness and overall lens comfort at 3 months and at 6 months, when the study ended. Tear meniscus height - a relatively new measurement of tear production - was also greater in the GLA supplementers compared to placebo.
Antioxidants, Exercise Boost Bones in Women
The results of a pilot study in 34 post-menopausal women suggest that a combination of antioxidant supplements and resistance training may help protect against bone loss. The women were assigned to 1 of 4 groups: 1) antioxidants plus exercise; 2) antioxidants and no exercise; 3) placebo plus exercise; or 4) placebo and no exercise. The antioxidants consisted of 600 IU vitamin E and 1,000 mg of vitamin C daily.
At the end of 6 months, measures of bone density revealed that only those women not exercising and getting the placebo experienced significant bone loss in the spine. In contrast, the bone density of those who exercised or took the antioxidants remained constant. These preliminary findings are promising and lend support to previous links seen between higher intake of antioxidants (e.g. lycopene) and better bone density in the spine of women and, for men, in the hip.
References

1. Al Biltagi M, et al. Omega-3 fatty acids, vitamin C and zinc supplementation in asthmatic children: a randomized, self-controlled study. Acta Pediatrica 98:737-42, 2009.
   
2. Ramel A, et al. Moderate consumption of fatty fish reduces diastolic blood pressure in overweight and obese European young adults during energy restriction. Nutrition [Epub May 30, 2009].
   
3. Kokke KH, et al. Oral omega-6 essential fatty acid treatment in contract lens association dry eye. Contact Lens Anterior Eye 31:141-6, 2008.
   
4. Chuin A, et al. Effect of combined antioxidants compared to resistance training on BMD in elderly women: a pilot study. Osteoporosis Inter 20:1253-8, 2009.
   
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Contact Lens Wear, Dry Eye & Fatty Acids
Contact Lens Wear Can Lead to Dry Eye
Most people are aware that dry eye is a pervasive problem. Estimated to affect up to 1 in 5 adults, it is the most common condition seen in ophthalmology practices. Lesser known, however, is that dry eye is also the most common complaint among those who wear contact lenses.
In some cases, people who already have existing, marginal dry eye can experience worsening of the condition when they begin to wear contact lenses. For others, the lenses themselves may lead to dry eye symptoms over time.
Disturbing the Tear Film
The tear film that hydrates and lubricates the optical surface of the eye is composed of several layers. There is an oily outer layer which helps prevent the tear fluid from evaporating, and an inner layer of fluid that also contains a mucous-like gel which allows the fluid to spread evenly over the surface. A normal and stable tear film is necessary in order to be a successful contact lens wearer who does not suffer from symptoms of dryness or sensation of grittiness.
When a contact lens is placed in the eye, the lens can alter the normal structure of the tear film and affect its rate of evaporation. Greater evaporation leads to increased osmolarity (saltiness or lower volume of tear fluid) - a good predictor of dry eye (1). Tear osmolarity is often elevated in contact lens wearers, and even more so in those who can't tolerate them.
Microvilli Losses
For those who have been wearing their lenses for many years, there may be another contributing factor. The continual rubbing of the lens across the surface of the cornea may result in some loss of the microscopic hair-like structures called microvilli that exist on the outermost layer of the cornea. The microvilli bind to the mucous-like gel in the tear fluid so that the tear film adheres well to the cornea and maintains a stable, uniform layer on the cornea.
It's believed that the constant movement of the contact lens across the surface of the cornea over years of wear may reduce the microvilli. In turn, this can destabilize the tear film and result in contact lens-induced dry eye. It is also thought that discontinuing lens use temporarily will help restore microvilli.
Strategies for More Successful Lens Wear
Contact lenses are often a good alternative for people who are bothered by the cosmetic appearance of eyeglasses or the limitation to activities that they pose. To have a comfortable experience with contact lenses, it's important to be under the care of an eye care practitioner to ensure that the lens fit and lens materials you currently have are the best possible choice for you.
The type of lens chosen may make a difference in reducing the chance for dry eye. While some research has not shown a difference in tear osmolarity between soft, water-containing lens and the rigid, gas-permeable type of lens, in some cases soft, high-water content lenses may not be the best choice (2). In general, the more water a soft contact lens contains, the more prone it is to become dehydrated. As water evaporates from the front of the water-containing lens during wear, the lens draws moisture from the tear film. In addition to choosing appropriate lens materials, your eye doctor may also recommend lubricating drops or other aids, and suggest ways to modify environmental factors that can exacerbate dry eye such as overheated rooms, use of hairdryers or uninterrupted time at the computer.
Important Fatty Acids Can Be Helpful
An additional strategy is to try supplemental GLA and EPA, fatty acids that can bolster one's own natural, inflammation-fighting ability. Whatever the cause of dry eye - insufficient tear production, evaporation, chronic allergy or other - the result is an inflammatory reaction, and the contact lens wearer with symptoms of dryness is no exception (3). Research suggests that fatty acid supplementation can help calm inflammation and improve dry eye symptoms (4). Balanced amounts of GLA and EPA work together to reduce production of pro-inflammatory compounds while increasing the manufacture of compounds that are anti-inflammatory.
References

1. Tomlinson A, et al. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci 47:4309-15, 2006.
   
2. Iskelei G, et al. Comparison of tear-film osmolarity in different types of contact lenses. CLAO J 28:184-6, 2002.
   
3. Kallinikos P, et al. Assessment of stromal keratocytes and tear film inflammatory mediators during extended wear of contact lenses. Cornea 25:1-10, 2006.
   
4. Barabino S, et al. Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component. Cornea 22:97-102, 2003.
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Right Nutrition and Avoiding Triggers Helps Combat Dry Eye Syndrome
Dry Eye Affects Millions of Americans
If you experience scratchy, red, burning, irritated, even excessively teary eyes, you may be suffering from dry eye, one of the most frequent problems seen by eye care practitioners. While the condition is more common among older women and men, and those with the autoimmune diseases rheumatoid arthritis or Sjögren's, it can impact healthy people of all ages: particularly those who wear contact lenses, have ocular surface inflammation from allergies, undergo LASIK corrective surgery, live in dry climates or spend long hours in front of the computer screen.
There are a number of practical steps you can take to reduce your risk of getting dry eye, or to help relieve symptoms if you already suffer dry eye discomfort.
The Role of Diet and Supplementation
There are now topical drugs available to fight the inflammation of dry eye, ocular procedures to help retain tears and ointments or drops that provide temporary relief. However, diet and supplementation can also make a difference. Supplementation with the fatty acid gamma-linolenic acid (GLA) has been reported to reduce symptoms, dampen inflammation and increase tear production in clinical studies of people with dry eye (1,2). Inflammation is an important factor in dry eye, and GLA can help the body build its own anti-inflammatory compounds. It can also support the oily outer layer of the tear film which helps prevent tear fluid from drying out.
Regular intake of fatty fish such as tuna and salmon has been linked with a lower risk of developing dry eye in older women (3). Eating ample amounts of fruits and vegetables is also a good strategy, as the antioxidants they contain can help fight the free radicals, which accompany inflammation. Vitamin C from citrus or bell peppers, for instance, is a key antioxidant in eye tissue.
Avoiding Environmental Triggers
A number of factors can worsen dry eye or even trigger the condition. If you smoke take steps to stop,
since both smoking and exposure to second hand smoke can be very eye-irritating. Avoid conditions that promote eye dryness such as very warm or overly air-conditioned rooms. Using a humidifier to keep the air moist can also be very helpful.

Having dry eye can affect the vision we need for daily activities like driving or reading. But new research from Ohio State University College of Optometry has shown that long periods at the computer or reading can also bring on dry eye or worsen its irritating symptoms (4).
Squinting Squelches the Blink Reflex
Squinting, a common practice among computer users or those trying to bring type into better focus, causes people to blink less often. Tears naturally evaporate when the eyes are open, and blinking is necessary to spread new tears produced by the tear glands. The Ohio State investigators hooked small electrodes to the lower lids of volunteers to measure the activity a muscle involved in both squinting and blinking.
When the volunteers squinted, they blinked half as often. They also reported more dryness and tearing. Earlier work by the same team found that people blinked 22 times per minute when relaxed, 10 times while reading a book, and 7 times when viewing text on a computer screen. Computer users can reduce the harmful effects on their eyes, by alleviating glare and the conditions that cause them to squint more often, according to the study's authors.

Minimizing Risks of Visual Discomfort
The Mayo Clinic offers these solutions to common risk factors that cause squinting and eye discomfort:
• Prolonged monitor viewing. Take frequent visual breaks (look at an object 20 feet away for a few seconds), and close your eyes periodically. Keep computer screen clean, and font size big enough.
  
  
• Glare from windows or lights. Position your monitor perpendicular to light sources and block window light with blinds. Use a glare screen on your display monitor, or tilt the screen to cut glare. Reduce overhead lighting and use "task" lighting.
References

1. Barbarino S et al. Cornea 22:97-101, 2003.
2. Macri A et al. Graefes Arch Clin Exp Ophthalmol (online, 2003).
3. Miljanovic B et al. Am J Clin Nutr.82:887-93, 2005.
4. Sheedy JE et al. Optom Vis Sci.82:905-11, 2005.
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GLA and Vision-Corrective Laser Surgery
Know someone who's scheduled for vision-corrective laser surgery? GLA may help!
LASIK or PRK Can Cause Temporary Dry Eye
Some people, who are appropriate candidates, opt for laser surgery to help correct their vision. The two most common types of procedures are LASIK (Laser In Situ Keratomileusis) and PRK (Photorefractive Keratectomy). These popular procedures use a laser or a combination of microsurgery and laser to reshape the eye's cornea. Reshaping the cornea alters the focusing power of the eye, allowing one to become less dependent upon glasses or contact lenses.
Having Dry Eye Before Surgery May Prolong or Worsen Symptoms Afterward
One common side-effect of the surgery is dry eye. It can make the cornea less sensitive, resulting in lower tear production and inflammation. The good news is that dry eye is temporary, typically lasting no more than a month. But symptoms may last longer and be more severe in people who already have dry eye before they undergo the surgery (1).
What Is Dry Eye Syndrome?
A common condition, dry eye has many causes. One of the most common reasons is the normal aging process. It's also associated with certain conditions such as rosacea and Parkinson's. Women frequently experience dry eye, especially as they enter menopause. Symptoms include itching, burning, or a gritty sensation - even tearing when the eye is irritated. Visual efforts like reading or computer time can aggravate symptoms, and other factors such as hot, dry, or windy climates; high altitudes; air-conditioning; and cigarette smoke are also contributors. Ironically, contact lens wear can also contribute to or worsen dry eye, which often leads people to laser surgery.
Special Fatty Acids May help
Italian researchers recently investigated the effects of fatty acids on dry eye in people undergoing PRK. Thirty patients were given supplements of linoleic acid and gamma-linolenic acid or GLA. Another group underwent PRK without the supplement. Compared to the untreated control patients, the group getting fatty acids were found to have significantly fewer symptoms of dry as measured by questionnaire. They also scored better in the Schirmer test-a method for measuring tear production-and their eyes were able to more readily clear a staining dye from their tears, reflecting better ocular surface sensitivity and tear clearance.
GLA is a specialized fatty acid with the ability to modify inflammation and support tear production (2-4). These researchers concluded that GLA as a precursor to anti-inflammatory compounds, could be helpful in increasing tear production and clearance after PRK (5).
HydroEye is a unique, oral formulation for dry eye relief. It provides GLA and nutrient cofactors that help dampen inflammation and support a healthy tear film.
References

1. Toda I et al. Laser-assisted in situ keratomileusis for patients with dry eye. Arch Opthalmol 120:1024-28, 2002.
2. Aragona P et al. Tear PGE1 levels in dry eye patients after treatment with essential fatty acids. Invest Ophthalmol Vis Sci 42:5259, 2001.
3. Bababino S et al. Efficacy of systemic linoleic and gamma-linolenic acid therapy in dry-eye syndrome with inflammatory component. ARVO Annual Meeting, Fl, May 2002, abstract 2105.
4. Horobin DF et al. Treatment of the sicca syndrome and Sjögren's syndrome with EFA, pyridoxine, and vitamin C. Prog Lipid Res 20:253-4, 1981.
5. Macri A et al. Effect of linoleic acid and gamma-linolenic acid on tear production, tear clearance and on the ocular surface after photorefractive keratectomy. Graefes Arch Clin Exp Ophthalmol (published online, May 27, 2003)
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GLA & EPA / DHA Combination Advantageous in Dry Eye
GLA and EPA Have Complementary Actions
The fatty acids gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect cellular processes involved in inflammation, including the production of eicosanoids. Prostaglandins are the major eicosanoids that are produced from specific fatty acids during inflammation:
• Anti-inflammatory prostaglandin E1 is derived from dGLA, a metabolite of GLA from the omega-6 family of fatty acids;
• Anti-inflammatory prostaglandin E3 is a derivative of EPA, an omega-3 fatty acid.
• Finally, the omega-6 arachidonic acid – abundant in meat and animal products – gives rise to pro-inflammatory prostaglandin E2.
It’s well known that inflammation plays a role in ocular surface dryness. Most dietary supplements investigated in dry eye have tested GLA or EPA and DHA. However, combining these fatty acids may optimize their ability to modulate inflammation.
Human studies, for example, have demonstrated that the addition of EPA and DHA in a balanced ratio to GLA prevents elevations in serum arachidonic acid (1,2), thus leading to decreased levels of pro-inflammatory prostaglandin. A combination of omega-3 and omega-6 fatty acids also results in lower arachidonic acid in the retinas and exorbital lacrimal glands in animals (3). A recently published study (4) lends credence to the idea that a GLA, EPA and DHA combination may provide advantages to supplementation with fatty acids from either the omega-3 or omega-6 family alone.
Study Design and Methods
Female Lewis rats were fed diets containing 1) GLA; 2) EPA and DHA; or 3) a combination of GLA, EPA and DHA for 2 months before the induction of dry eye using a continuous delivery of scopolamine, and during scopolamine treatment. Two, 10 and 28 days after dry eye-induction, clinical signs of corneal dryness were evaluated in vivo using fluorescein staining. Major histocompatibility complex Class II (MHC-II) expression and mucin (rMuc5AC) production in the conjunctival epithelium were evaluated by immuno-staining. Lipids and prostaglandins were analyzed from the exorbital lacrimal gland.
Results
Dietary supplementation of omega-6 (GLA) and/or omega-3 fatty acids (EPA and DHA) improved the clinical signs of dry eye, although at a moderate level. All three of the fatty acid enriched diets minimized the occurrence of corneal keratitis after 28 days of treatments, and all the diets partially prevented a decrease in mucin.
The combined omega-6 and omega-3 diet, however, led to a lower arachidonic acid content in phospholipids (where fatty acids are stored), and a higher dGLA content when compared to the GLA-only enriched diet. Further, the over-expression of MHC II in the conjunctival epithelium caused by dry eye induction was significantly reduced only with the GLA + EPA + DHA diet after 28 days of treatment.
Comments
According to the study authors, these results point out the efficacy of combining omega-3 with omega-6 GLA. GLA, dGLA, EPA and DHA have all been described as decreasing inflammation by reducing the expression of MHC II and inhibiting the production of inflammatory cytokines such as TNF-a and IL-1ß. In this study, only the combined fatty acids reduced MHC II expression.
These findings are in agreement with those from a pilot clinical trial conducted by the same researchers (5). In this trial, 3-month treatment with combined GLA, EPA and DHA demonstrated improved symptoms, and suggested a beneficial effect on the clinical signs of ocular dryness. The authors state that GLA with EPA and DHA may be useful in a dry eye therapy strategy along with classical therapy such as artificial tears.
References
1. Barham JB, et al. Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans. J Nutr 130:1925-31, 2000.
2. Laidlaw M, et al. Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipid profiles in women. Am J Clin Nutr 77:37-42, 2003.
3. Schnebelen C, et al. Nutrition for the eye: Different susceptibility of the retina and lacrimal gland to dietary omega-6 and omega-3 polyunsaturated fatty acid incorporation. Ophthalmic Res 41:216-24, 2009.
4. Viau S, et al. Efficacy of a 2-month dietary supplementation with polyunsaturated fatty acids in dry eye induced by scopolamine in a rat model. Graefes Arch Clin Exp Ophthalmol 247:1039–50, 2009.
5. Creuzot C, et al. Improvement of dry eye symptoms with polyunsaturated fatty acids. J Fr Ophtalmol 29:868–73, 2006.
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GLA Improves Comfort in Contact Lens-Related Dry Eye
Dry Eye Common in Contact Lens Wearers
Contact lens wearers commonly report a sensation of 'dryness' - a symptom that often results in reduced wear time or discontinued use. In most cases of contact lens-induced dry eye, objective signs are lacking and a diagnosis is based on symptoms alone. However, it has been demonstrated that intolerant contact lens wearers show significantly reduced tear stability and volume compared to successful wearers.
A variety of conventional strategies have been employed to alleviate contact lens-induced dry eye including use of artificial tears, changing lens parameters, or preserving tears with punctal plugs. However, novel treatment strategies using anti-inflammatory or immune modulating agents may also be effective. A recent pilot study, for example, offers evidence that cyclosporine may be beneficial in contact lens intolerant patients (1).
Oral GLA of Benefit in Inflammatory Dry Eye
Another more 'natural' approach involves the use of supplemental gamma-linolenic acid (GLA), an omega-6 fatty acid with anti-inflammatory properties found in oils derived from black currant seeds and the evening primrose plant. Several small trials testing GLA and linoleic (LA) oil in dry eye syndrome with an inflammatory component report reduced ocular surface inflammation and symptom improvement (2,3). These beneficial findings led researchers to examine the effects of GLA in contact-related dry eye patients (4).
Study Design and Methods
In this randomized, double-blind controlled trial, 76 female soft contact lens wearers with documented dry eye or borderline dry eye (McMonnies score =10), were treated for 6 months with GLA (300 mg daily) from evening primrose oil (EPO) or placebo (olive oil).
Participants were examined at 3 time points: baseline and at 3 and 6 months. At each exam, subjects answered a questionnaire relating to lens comfort and dry eye symptoms, and underwent a series of tests of tear film characteristics (tear meniscus height, break-up time), meibomian gland function (lipid layer thickness and quality), and ocular surface parameters (hyperaemia and staining).
Results
The GLA group showed a significant improvement in the specific symptom of 'dryness' at 3 and 6 months (p <0.01) as well as significant improvement in overall lens comfort at 6 months (p<0.01). Tear meniscus height was increased in the GLA group at 6 months relative to baseline (p<0.01), although all other objective signs were unchanged (See figures 2 and 4).



Comments
This study provides evidence for a beneficial effect of oral GLA in alleviating symptoms and improving overall lens comfort in patients suffering from contact lens associated dry eye. According to the authors, this may be via a reduction in ocular surface inflammation that has been previously documented in contact lens wearers. An effect on tear secretion could also be a contributing factor. The authors indicate that "future studies will investigate the efficacy of a combined preparation (GLA, EPA and DHA), since it is likely that omega-3 fatty acids could act synergistically with omega-6 to enhance the therapeutic effect of each fatty acid".
References
1. Hom MM. Use of cyclosporine 0.05% ophthalmic emulsion for contact lens intolerant patients. Eye Contact Lens 32:109-11, 2006.
2. Barabino, M et al. Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component. Cornea 22:97-101, 2003.
3. Aragona P, et al. Systemic omega-6 essential fatty acid treatment and PGE1 tear content in Sjögren's syndrome patients. Invest Ophthalmol Vis Sci 46:4474-9, 2005
4. Kokke KH, et al. Oral omega-6 essential fatty acid treatment in contact lens associated dry eye. Contact Lens Anterior Eye 31:141-6, 2008.
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GLA: A Safe & Effective Anti-Inflammatory Omega-6 Fatty Acid
Inflammation: Friend and Foe
The acute inflammatory response defends against invading microorganisms and damaged cells, and is essential for wound healing & tissue repair. Chronic inflammation, however, damages tissues and can lead to or worsen chronic diseases such as arthritis, heart disease & dry eye syndrome.
GLA as an Anti-Inflammatory Nutrient
A recent review underscores the role of the fatty acid gamma linolenic acid (GLA) in modulating the inflammatory response (1). GLA has gained recognition over the last few decades for its anti-inflammatory and anti-cancer actions. Some key findings from controlled clinical trials include:
• In arthritics, several trials report that GLA reduced inflammation, symptoms, and the requirement for NSAIDs
• In inflammatory dry eye, GLA improved symptoms and reduced inflammation; in PRK patients, GLA relieved symptoms, and increased tear production and clearance; in Sjögren's patients, GLA eased ocular discomfort by reducing inflammation and increasing tear content of PGE1
• In diabetics, GLA improved nerve conduction velocity leading to improved blood flow and reduced tingling of extremities
• In patients with acute lung injury, GLA along with EPA improved gaseous exchange
• In breast cancer patients, GLA improved the effectiveness of tamoxifen, reduced side-effects, and hastened therapeutic response
• In uremic pruiritis, a common problem in hemodialysis patients, topically applied GLA relieved symptoms
Sources & Rationale for Supplementation
Dietary intake of GLA is typically negligible as GLA is present only in trace amounts in some green leafy vegetables and nuts. Supplemental sources include the oils of: borage (Borage officinalis), 20-26% GLA; black currant (Ribes nigrum), 15-18%; and evening primrose (Oenoethera biennis), 8-12%. According to Tufts researchers, black currant seed oil is a preferred source because it contains 13-16% of the omega-3 fatty acid alpha-linolenic as well as GLA. Examining the effects of black currant seed oil (vs. placebo) in healthy elderly subjects, researchers from Tufts found that GLA reduced levels of PGE2 and improved immune function (2).
GLA is produced in the body as an intermediate in the metabolism of linoleic acid (LA). However this reaction is very slow and further restricted by alcohol use, stress, smoking, saturated and trans-fatty acid intake, and deficiencies of magnesium, vitamin B6 and zinc. These factors - as well as hypertension, arthritis, psoriasis and diabetes - impair the activity of delta-6-desaturase, the enzyme that converts linoleic acid to GLA. Administering oral GLA is a means to bypass this often inefficient and rate-limiting step in the metabolism of LA to GLA.
Anti-Inflammatory Mechanism of Action
GLA is rapidly converted to dihomo GLA (DGLA) which is incorporated into cell membrane phospholipids. When released by the action of the enzyme phospholipase A2, DGLA competes with arachidonic acid for the enzymes COX and LOX. Arachidonic acid is the omega-6 found abundantly in meat and dairy, and the precursor to pro-inflammatory eicosinoids like PGE2.
The COX products of DGLA include prostaglandins of series 1 (PGE1) and thromboxane A1. These products exert anti-inflammatory, anti-aggregation and vaso-dilatory actions.
A key LOX product of DGLA, 15-HETrE, inhibits production of leukotriene B4 from inflammatory cells including neutrophils. Some research suggests that DGLA may act directly on T-cells to modulate immune response in diseases such as rheumatoid arthritis.
Anti-Cancer Mechanisms of Action
Pre-clinical research indicates that the anti-cancer properties of GLA include: direct cytotoxic action on cancer cells, anti-angiogenic action in tumor cells, stimulation of apoptosis, gene activation, and the effects of DGLA eicosinoids. Preliminary clinical studies suggest that GLA may have benefit in some cancers. GLA injected directly into tumor cells of patients with advanced glioma significantly reduced tumor mass.
Safety of Supplemental GLA
Supplemental GLA has been safely administered in clinical trials at oral doses of 2.8 grams per day or less, for up to a year (3-5). GLA-rich oils have also been commonly used in the U.S. for over 20 years, with no reports of serious adverse events or effects (6).
Americans, who generally obtain an excess of omega-6 fats through over-consumption of meat, dairy, vegetable cooking oils and shortenings, are advised to consume more omega-3s from fatty fish and nuts. The amount of omega-6 fatty acids present in common doses of GLA-rich oil do not make a significant contribution to overall fat intake - typically about 67 grams daily for a 2000 kcal diet with 30% of calories from fats. Further, black currant seed oil contains a recommended ratio of omega-6 to omega-3 fats.
GLA & EPA: Complementary Actions
One concern related to DGLA, is that it could be further metabolized to arachidonic acid with subsequent pro-inflammatory effects. This is not relevant in inflammatory cells such as neutrophils, since these cells lack enzyme (delta-5-desaturase) activity needed to convert DGLA to arachidonic acid (7). Importantly, inflammatory cells from subjects supplemented with GLA produce significantly less pro-inflammatory leukotriene B4 (8,9) .
In contrast to inflammatory cells, high levels of supplemental GLA have been shown in some but not other studies to elevate serum arachidonic acid levels. Human studies, however, have demonstrated that the addition of fish-derived omega-3 EPA in a balanced ratio to GLA, blocks the activity of delta-5-desaturase and prevents elevations in serum arachidonic acid (10,11).
Co-ingesting similar levels of EPA and GLA increases cellular membrane content of both DGLA and EPA (precursor to anti-inflammatory eicosinoids). In short, this supplementation strategy successfully maintains the anti-inflammatory capacity of GLA and increases serum EPA, without causing accumulation of arachidonic acid.
Flaxseed oil is a concentrated source of omega-3 alpha linolenic acid. However, conversion of this fatty acid to EPA is limited, and further metabolism to DHA is very low or negligible (12). Typically, only 15-40% of alpha linoleic is converted to EPA This may, in part, explain why omega-3 fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, have been found to benefit cardiovascular disease outcomes in primary- and secondary-prevention studies (13). Thus GLA-enriched oils are more effectively paired with fish oil rather than flaxseed oil to promote the complementary actions of GLA and EPA.
References
1. Kapoor R, et al. Gamma Linolenic Acid: An anti-inflammatory omega-6 fatty acid (Review) Curr Pharm Biotech 7:531-34, 2006.
2. Wu D, et al. Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects. Am J Clin Nutr 70: 536-543, 1999.
3. van der Merwe, et al. The effect of gamma-linolenic acid, an in vitro cytostatic substance contained in evening primrose oil, on primary liver cancer. A double- blind placebo controlled trial. Prostaglandins Leukot Essent Fatty Acids 40:199-202, 1992.
4. Zurier RB, et al. Gamma-linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum39:1808-17, 1996.
5. Keen H, et al. Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-Linolenic Acid Multicenter Trial Group. Diabetes Care 16:8-15, 1993.
6. Physicians' Desk Reference for Nutritional Supplements, 1st Edition, ISBN 1-56363-364-7, p. 173.
7. Chilton-Lopez T, et al. Metabolism of GLA in human neutrophils. J Immunol 156:2941-47, 1996.
8. Johnson M, et al. Dietary supplementation with GLA alters fatty acid content and eicosanoid production in healthy humans. J Nutr 127:1435-44, 1997.
9. Ziboh VA, et al. Dose-response effects of dietary GLA-enriched oils on human polymorphonuclear-neutrophil biosynthesis of leukotriene B4. Am J Clin Nutr 55:39-45, 1992.
10. Barham JB, et al. Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans. J Nutr 130:1925-31, 2000.
11. Laidlaw M, et al. Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipid profiles in women. Am J Clin Nutr 77:37-42, 2003.
12. Burdge G, et al. Alpha linolenic metabolism in adult humans. Eur J Lipid Sci Tech 107:426-39, 205, 2005.
13. Wang C, et al. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J of Clin Nutr 84:5-17, 2006.
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Supplemental GLA Improves Dry Eye in Sjögren's Syndrome
Inflammation and Sjögren's Syndrome
Affecting more than 1.4 million Americans, Sjögren's syndrome is an autoimmune disorder in which immune cells attack and destroy the glands that produce tears and saliva. The hallmark symptoms of the disorder are dry mouth and dry eyes. Sjögren's syndrome is also frequently associated with rheumatic disorders such as rheumatoid arthritis.
T-cell infiltration and markers of immune activation have been noted in both the conjunctiva and lacrimal glands of these patients. Topical anti-inflammatory treatment of patients with dry eye reportedly produces a significant reduction of activated lymphocyte in the conjunctiva, thus demonstrating the potential for anti-inflammatory treatment of dry eyes.
Anti-inflammatory Activity of GLA
Gamma-linolenic acid (GLA) and its precursor linoleic acid (LA) are essential fatty acids found in certain plant seed oils such as black currant seed oil. Oral administration of GLA and LA has been shown to have beneficial effects in the treatment of chronic inflammatory disorders such as rheumatoid arthritis, and several pilot studies conducted in the 1980's suggest that these fatty acids may also benefit the ocular status of patients with Sjögren's.
GLA is metabolized to dihomo-linolenic acid (DGLA), the immediate precursor of PGE1, an eicosanoid with known anti-inflammatory action. In addition, both GLA and DGLA modulate the immune responses by acting directly on T lymphocytes. Researchers from the University of Messina in Italy now report that modest amounts of supplemental GLA and LA raise PGE1 tear content in Sjögren's, and improve signs and symptoms of ocular discomfort in these patients.
Design and Methods
This randomized, double-blind, controlled trial involved 40 patients with primary Sjögren's Syndrome divided into 2 groups. One group received GLA (15 mg) and LA (112 mg) twice daily for 1 month (GLA group), while the other group received placebos. Subjects underwent 3 examinations: baseline (T0), after 1 month (T1), and 15 days after treatment was suspended (T2). At each exam, the following tests were performed: tear sampling from the inferior meniscus, TBUT, fluorescein stain of the ocular surface, and tear basal secretion. A symptom score was also obtained each time. PGE1 was evaluated by enzyme immunoassay, and PGE1 content of tears was the primary endpoint.
Results
Tear PGE1 levels were significantly increased in the GLA group after 1 month of treatment. Fifteen days after treatment was halted, a significant reduction of the PGE1 levels toward baseline was observed. The symptom score was significantly lower in the GLA group after 1 month, with several symptoms (burning, foreign body sensation and dryness) remaining improved after treatment was stopped. The corneal fluorescein stain in this group also showed a significant improvement after the first month, which was sustained 15 days after treatment cessation.
No statistically significant differences were found for the other tests. In contrast to the GLA group, no statistically significant changes were noted in the placebo group at all examination time points. These results are summarized in the table below (group 1 = supplemented; group 2 = placebo).


Conclusions
According to the authors, these results indicate that supplemental GLA and LA effectively increases PGE1, an indicator of anti-inflammatory activity, improves ocular surface status and reduces dry eye symptoms.
Reference
Aragona P, et al. Systemic omega-6 essential fatty acid treatment and PGE1 tear content in Sjogren's syndrome patients. Invest Ophthalmol Vis Sci 46:4474-9, 2005.
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Dry Eye More Common Among Diabetics
According to a report released in May, an estimated 18 million Americans now have diabetes and another 20 million have impaired glucose tolerance that can lead to the full-blown disease. The prevalence of type 2, in fact, has tripled in the last 30 years along with the steady upsurge in obesity. In addition to facing higher rates of heart disease and potential complications such as neuropathy and retinopathy, diabetics are also more likely to suffer from dry eye according to findings from a recent prospective study (1).
Researchers followed the medical records of nearly 160,000 patients, 22,382 of them diabetics, in one of Israel's largest HMOs for 1 year. All filled prescriptions for ocular lubricants were documented, and the proportion of ocular lubrication consumers among diabetic and non-diabetic patients aged 50 and older was compared. HbA1c was also measured to examine the relationship between glycemic control and lubricant use.
A significantly higher percentage of diabetics (21%) were shown to receive the medications compared with non-diabetics (14%) in all age groups and for both sexes (Fig 1). Significantly more diabetics were frequent users of the medication (> 12 filled prescriptions yearly) than were KCS patients without diabetes. A clear trend between higher lubricant use and poorer glycemic control, regardless of age, was also observed.
The findings suggest that blood sugar control is important in preventing or reducing KCS in diabetics. According to the authors, small vessel damage and autonomic neuropathy may reduce lacrimal gland function. Decreased corneal sensitivity, which interrupts tearing reflex, could also play a role.
Commentary
 
Results from several small controlled trials report that supplemental gamma-linolenic acid (GLA) improves symptoms of dry eye in KCS and post PRK (2,3). While this fatty acid has not been evaluated specifically in diabetic patients, there is evidence that GLA metabolism is impaired in diabetes (4). Additionally, GLA (480 mg daily) has been shown in a placebo-controlled trial to improve diabetic neuropathy (5).
Figure1. Percent of diabetic and non-diabetic patients who filled prescriptions for ocular lubrication, stratified by age. The percent of diabetic patients prescribed lubrications was statistically significantly larger than the percent of non-diabetic patients (X2 test, P < .0001 for all age groups).
 

References
• Kaiserman, et al. Dry eye in diabetic patients. Am J Ophthalmol 139:498-503, 2005.
• Barbarino S, et al. Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component. Cornea 22:97-101, 2003.
• Macri, et al. The effect of LA and GLA on tear production, tear clearance and on the ocular surface after PRK surgery. Graefes Arch Clin Exp Ophthalmol 241:561-6, 2003.
• Mikhailidis DP, et al. The effect of DGLA on platelet aggregation and prostaglandin release, erythrocyte membrane fatty acids and serum lipids: evidence for defects in PGE1 synthesis and delta-5 desaturase activity in insulin-dependent diabetics. Diabetes Res 3:7-12, 1986.
• Keen H, et al. Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-linolenic acid multicenter trial group. Diabetes Care 16:8-15, 1993.
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Study Supports HydroEye®* as Useful Pre-LASIK Strategy
Introduction
Transitory dry eye is a common complication after PRK and LASIK, lasting longer in patients with pre-operative dry eye (1). The anti-inflammatory properties of the fatty acid gamma linolenic acid (GLA) have long been known, and recent studies report that supplemental GLA increases tear concentrations of anti-inflammatory prostaglandin E1 (2,3), and increases tear production while reducing dry eye symptoms in post-PRK patients (4).
Consistent with these findings, are the results from several preliminary investigations of HydroEye®*, reported by Frank A. Bucci Jr, MD at the 2002 and 2003 ASCRS meetings. In the first study, administration of HydroEye daily to 13 normal patients was found to increase mean tear lactoferrin levels by 60% at the end of 8 weeks. Additionally, 12 pre-LASIK patients given HydroEye daily 1-4 weeks prior to LASIK, experienced a 40% increase in lactoferrin when measured the day before the procedure.
Follow-Up Trial
In a follow-up study reported at ASCRS earlier this year (5), Dr. Bucci evaluated the effects of pre-treatment with HydroEye in 40 patients undergoing bilateral LASIK. Twenty patients with a history of evaporative or aqueous-deficient dry eye were assigned to take the daily recommended dose of HydroEye for one month before surgery, continuing for a month post-operatively.The remaining 20 patients, age-matched but with no prior history of dry eye, served as untreated controls.
Tear lactoferrin levels were measured (Tear Profile Analyzer) at baseline, on the day of the procedure, and at one day and one month after surgery. At the beginning of the study, the treated group had a higher incidence of ocular surface disease and a lower lactoferrin level than the control group (.95 vs. 1.1 ng/ml, respectively).
In the treated patients, mean lactoferrin increased a significant 32% during the pre-treatment period, becoming significantly higher (mean 24%) than the control group by the day of surgery. Lactoferrin levels dropped one day post-op in both groups. However the post-surgery decrease was less marked in the treated compared to untreated patients (.88 v .77 ng/ml respectively), with lactoferrin levels still 12% higher in those taking HydroEye. Lactoferrin rose in both groups during the month following surgery, with levels remaining slightly above baseline measurements in the treated group. No difference in lactoferrin was noted between the two groups at the end of this period.

Levels of tear lactoferrin, an indicator of ocular surface health, have been shown to be decreased in those with tear-deficient dry eye, according to the study's author. "Against that background, the results of this study support the pre-operative, prophylactic use of oral omega fatty acids in patients with mild to moderate risk for dry eye after LASIK," Dr. Bucci concluded.
*HydroEye is a patented formulation containing GLA, omega-3 fatty acids, antioxidant vitamin C, and other nutrients needed to convert fatty acids to anti-inflammatory prostaglandins.
References

• Toda I, et al. Laser-assisted in situ keratomileusis for patients with dry eye. Arch Opthalmol 120:1024-28, 2002.
• Aragona P, et al. Tear PGE1 levels in dry eye patients after treatment with essential fatty acids. Invvest Ophthalmol Vis Sci 42:5259, 2001.
• Barabino S, et al. Systemic linoleic and gamma-linolenic acid therapy in dry-eye syndrome with inflammatory component. Cornea 22(2): 97–101, 2003.
• Macri A, et al. Effect of linoleic acid and gamma-linolenic acid on tear production, tear clearance and on the ocular surface after photorefractive keratectomy. Graefes Arch Clin Exp Ophthalmol (published first online, 05/27/2003) Full paper available upon request.
• Guttman, C. Omega fatty acid supplements useful strategy before LASIK. Ophthamology Times, Nov 1, 2003.
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Oral Omega Fats, GLA & LA, Increase Tear Production After PRK
Introduction:
PRK is known to cause a temporary reduction in corneal sensitivity, leading to tear film changes, lowered reflex tearing, and production of inflammatory cytokines and free radicals. Transitory dry eye is a common complication after PRK and LASIK, lasting longer in patients with preoperative dry eye (1).
The anti-inflammatory properties of the fatty acid GLA have long been known. Recent studies report that oral administration of GLA and LA leads to a significant increase in tear concentrations of anti-inflammatory prostaglandin E1 (2,3), and reduces the symptoms of dry eye (2). The aim of this study was to evaluate the effects of GLA and LA on tear production, tear fluorescein clearance, dry eye symptoms, and the ocular surface after PRK (4).
Methods:
In this randomized, controlled trial, 31 patients received modest amounts of oral GLA and LA 3 days prior to 30 days after undergoing PRK. Another 29 patients underwent PRK without the supplement, serving as controls. The following measurements were made at baseline and at the end of the study period: symptom questionnaire, Schirmer 1 test, fluorescein clearance test using standardized visual scale and corneal fluorescein staining.
Results:
All 60 patients completed the study. Statistical analysis showed a significant mean difference between the groups for dry eye symptoms, fluorscein clearance, and Schirmer's results. Compared to controls, the treated group had lower symptom scores, greater Schirmer test values, and more favorable fluorescein clearance scores [See Figures 1-3]. Both groups showed no signs of corneal staining at baseline. While more areas stained in controls than treated patients at 1 month post-surgery (0.09 ± 0.10 vs. 0.25 ± 0.21 respectively), the difference was not significant. The researchers concluded that oral precursors of prostaglandin E1, GLA and LA, could be helpful in increasing tear production and clearance after PRK.
Figure 1. Results of symptoms questionnaire (mean score) before starting study (T0) and 1 month after PRK (T1). (*P<0.05)

Figure 2. Results of Schirmer 1 test (mm/5 min) before starting study (T0) and 1 month after PRK (T1). (*P<0.0001)

Figure 3. Results of fluorescein clearance test by means of visual scale (mean score) before starting study (T0) and 1 month after PRK (T1). (*P<0.0001)

References

• Toda I et al. Laser-assisted in situ keratomileusis for patients with dry eye. Arch Opthalmol 120:1024-28, 2002.
• Aragona P et al. Tear PGE1 levels in dry eye patients after treatment with essential fatty acids. Invvest Ophthalmol Vis Sci 42:5259, 2001.
• Barabino S et al. Systemic linoleic and gamma-linolenic acid therapy in dry-eye syndrome with inflammatory component. Cornea 22(2): 97–101, 2003.
• Macri A et al. Effect of linoleic acid and gamma-linolenic acid on tear production, tear clearance and on the ocular surface after photorefractive keratectomy. Graefes Arch Clin Exp Ophthalmol (published first online, May 27, 2003) Full paper available upon request.
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A Study of Preexisting Dry Eye as a Risk Factor After LASIK Surgery
Due to contact lens intolerance, dry eye is a major reason for patients to consider LASIK. Dry eye is also a common post-LASIK complication, with compromised tear function and ocular surface typically lasting for at least one-month after surgery. Recovery time after surgery is also increased when dry eye develops. These factors led a group of researchers to investigate whether preoperative dry eye affects the visual outcome and incidence of complications after LASIK, and whether it is a risk factor for severe dry eye after surgery.
Methods:
The investigators divided 543 eyes (290 patients) into three groups: those without dry eye (NDE), those with probable dry eye (PDE), and subjects with definite dry eye (DE). Subjects were diagnosed for DE or PDE and categorized into one of the three groups according to the modified criteria of the Japanese Dry Eye Association, which included the Schirmer test with anesthesia, tear Break-Up Time (BUT), fluorescein and rose bengal staining of the ocular surface, and symptom assessment. Follow-up tests were performed at 3, 6, and 12 months after the procedure. To evaluate the effectiveness of LASIK correction, uncorrected (UCVA), best-corrected visual acuity (BCVA), and manifest refraction in the spherical equivalent were examined at 1, 3, 6, and 12 months.
Results:
No significant differences were found among the groups in UCVA and BCVA, except at 1 month, when UCVA was better in the NDE than in the DE group (p>.03). In the DE group, manifest refractive deviation was slightly larger than in the NDE group only at 3 months (p>.01).
The mean results of the Schirmer test were lower in both the DE and PDE subjects compared with the NDE group at all follow-ups after LASIK. Tear BUT was shorter in the DE compared to the NDE group before and at post-LASIK follow-ups. For ocular surface abnormality, fluorescein scores were higher in the DE than the NDE group before and after LASIK up through the one-year mark. Similar results were found with the rose bengal scores.
Dryness was significantly more severe for the DE group compared to the NDE group before LASIK and at 3, 6, and 12 months. This also held true for the PDE vs. the NDE patients at 6 months and 1 year (See figure 1).

Conclusions:
The results indicate that the safety and efficacy of LASIK are not affected by preexisting dry eye status. However, preoperative dry eye is a risk factor for severe postoperative dry eye with lower tear function, more vital staining of the ocular surface, and more severe symptoms. Bottom line: those that start out with dry eye suffer more discomfort over a longer period. This is a significant problem, as more than 75% of the patients who undergo LASIK at their clinic have dry eye at the outset according to these investigators.
HydroEye^® is a patented, oral nutritional formulation for dry eye relief. More than 2000 doctors recommend it to their dry eye patients, and many report that it helps reduce dry eye symptoms in their LASIK patients. HydroEye has been reported to increase lactoferrin levels (an indicator of ocular surface health) by a mean of 40% in pre-LASIK patients.
References

• Toda I, et al. Laser-assisted in situ keratomileusis for patients with dry eye. Arch Ophthalmol 120:1024-28, 2002.
• Aras G, et al. Decreased tear secretion after laser in situ keratomileusis for high myopia. J Refract Surg. 16:362-4, 2000.
• Toda I, et al. Dry eye after laser in situ keratomileusis. Am J Ophthalmol 132:1-7, 2001.
Figure 1 appears courtesy of Archives of Opthalmology, originally appearing in reference #1, above.
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Black Currant Seed Oil and EFAs in Dry Eye and Immunity
Studies have shown that dry eye patients experience a chronic inflammatory cycle, causing symptoms and impacting tear production. A Phase III FDA study of cyclosporine, an immunomodulatory drug, demonstrated that in moderate and severe cases of Sjögren's syndrome and keratoconjunctivitis sicca (KCS), markers of inflammation were significantly reduced from baseline following treatment with this drug. However, this potent immunomodulatory drug is not a first-line defense.
A more effective and preventive approach may be to address the biochemical basis of a healthy and intact tear film. Studies have shown that nutritional supplementation with omega-3 and omega-6 fatty acids and nutrient cofactors involved in the biosynthesis of the prostaglandin PGE1 result in reduced symptoms in dry-eye and KCS patients (1,2). PGE1 is necessary for tear secretion and also regulates inflammation. Essentially, in the event of reduction of PGE1 synthesis (due to a deficiency of omega-3 and omega-6 fatty acids), there is overproduction of series 2 prostaglandins (PGE2). Increased PGE1 production is anti-inflammatory because it down-regulates PGE2 production, and thus reduces over-reactive B-cell activity and may be a regulator of the arachidonic acid cascade. Wu and colleagues carried out a placebo-controlled study of the effect of dietary supplementation with black current seed oil (BCSO) on immune response in healthy subjects 65 years or older (3).
Methods:
This was a randomized double-blind study. Forty patients were randomized to receive either 750 mg BCSO or 750 mg soybean oil. BCSO contains linoleic acid and 15% gamma-linolenic acid (GLA) - both omega-6 fatty acids, as well as the omega-3 fatty acids alpha-linolenic acid and stearidonic acid. The ratio of omega-3 to omega-6 fatty acids in BCSO is about 1 to 4. The level of vitamin E intake in both groups was controlled equally. Supplementation continued for 2 months.
Results:
BSCO supplementation, significantly increased plasma concentrations of gamma-linolenic acid (omega-6), alpha-linolenic acid (omega-3), and dihomo-gamma-linolenic acid compared with baseline. These increases were not evident in the control group. The BCSO group exhibited enhanced response to tetanus toxoid. In the BCSO group, stimulated PGE2 production was significantly reduced from baseline (488 ng/L to 258 ng/L). This was significantly (p<0.05) different from the control (soybean oil) group, which did not exhibit this reduction (Figure). The authors concluded that BCSO has a moderate immune enhancing effect attributable to reduction of PGE2 production.


Comment:
This study and previous research suggests that the combination of omega-3 and omega-6 fatty acids in black current seed oil both results in increased PGE1, which both stimulates aqueous tear secretion and reduces the production of PGE2.
ScienceBased Health's HydroEye^® is a proprietary blend of BCSO (rich in both omega-3 and 6 fatty acids), Cod Liver Oil (additional omega-3 fatty acids, Vitamin A, and eicosanoids), Vitamins B6 and C and Magnesium. This optimal ratio of omega-3 and omega-6 fatty acids along with the essential cofactors for the PGE-1 pathway, results in increased PGE1 production. PGE1 both stimulates aqueous tear secretion and reduces inflammation by down-regulating production of PGE2 (enhancing T-cell production and inhibiting over-reactive B-cells).
References

• Horrobin DF, Campbell A, McEwen CG: Treatment of the Sicca Syndrome and the Sjögren's Syndrome with E.F.A., Pyridoxine and Vitamin C. Prog Lipid Res 8(4): 253-4, 1981
• Oxholm P, Manthorpe R, Prause JU, Horrobin D: Patients with Primary Sjögren's Syndrome Treated for 2 Months With Evening Primrose Oil. Scand J Rheumatology 1986; 15:103-108.
• Wu D, Meydani M, Leka L, et. al.: Effect of dietary supplementation with black current seed oil on the immune response of healthy elderly subjects. Am J Clin Nutr 1999;70:536-543.
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Dry Eye: A Clinical Trial of Essential Fatty Acids
In the previous EduFacts we summarized preliminary work by Horrobin and colleagues (1) which indicated that an effective approach to the treatment of dry eye disorders may be to address the biochemical basis of an intact tear film. In this preliminary study the authors had evaluated the use of supplemental intake of the essential fatty acids (EFA); linoleic and gamma linolenic acids; vitamin B6 ; and vitamin C to treat dry eye. These nutrients are necessary components of the pathway for biosynthesis of prostaglandin E1 (PGE1), which is necessary for aqueous tear secretion by the lacrimal glands. The rationale for their study was based on earlier research showing that gamma linolenic acid (GLA), an upstream metabolite of the EFA linoleic acid, was lower among patients with Sjögren's Syndrome. This suggested a breakdown in the biochemical pathway which might be remedied by supplying both GLA, linoleic acid and the vitamin cofactors involved.
Another controlled study of treatment with precursor EFAs was performed by Oxholm and colleagues on patients with primary Sjögren's Syndrome (2).
Methods:
28 patients with primary Sjögren's Syndrome were studied in a "cross-over" clinical study. Each patient received either Efamol (73% cis-linoleic acid, 9% gamma linolenic acid) or placebo for 8 weeks. Dosing was 6 3g capsules daily. Then each patient was "crossed-over" and received the opposite treatment for 8 more weeks. The initial treatment assignment was randomly chosen for each patient and the study was double masked - neither patients nor clinicians knew the treatment given to the patient. Clinical tests for keratoconjunctivitis sicca (KCS) included Schirmer test, tear-break-up-time, and Bijstervald score. These tests were evaluated before and after treatment. A combined ocular score was also computed. In addition the levels of DGLA (a metabolite of linoleic acid produced during biosynthesis of PGE1) were measured in serum and in erythrocytes before and after treatment.
Results:
Statistically significant baseline-to-post-treatment improvement in the overall ocular score was found in the Efamol group (p<0.05). Fewer patients in the control group experienced improvement (baseline-to-post-treatment) in ocular score. Furthermore, levels of the metabolite Di-hommo-gamma linolenic acid (DGLA) were increased significantly in both plasma (25% increase, p<0.001), and erythrocytes (10% increase, p<0.05) during Efamol treatment but not placebo treatment.

References

• Horrobin DF, Campbell A, McEwen CG: Treatment of the Sicca Syndrome and the Sjögren's Syndrome with E.F.A., Pyroxidine and vitamin C. Prog Lipid Res 8(4): 253-4, 1981.
• 2. Oxholm P, Manthorpe R, Prause JU, Horrobin D: Patients with Primary Sjögren's Syndrome Treated for 2 Months With Evening Primrose Oil. Scand J Rheumatology 1986; 15:103-108.
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Dry Eye: A Preliminary Study of Essential Fatty Acids, Vitamins C & B6
Treatment of Keroconjunctivitis Sicca and other surface disorders is generally palliative, with the administration of lubricating drops. Current topical products are formulated to both lubricate the eye and enhance certain characteristics of the tear film. For example, hypotonic solutions reduce osmolarity and mucolytic agents can decrease the symptoms of excess mucin strands. Other additives may help lower tension at the water-oil interfaces and mimic some actions of the mucin network. However these palliative measures are temporary and do not address the underlying causes. For example, reduced osmolarity upon instillation may last only about 10 minutes.
A more effective approach may be to address the biochemical basis of an intact tear film. D.F. Horrobin and colleagues have carried out some preliminary studies of the use supplemental intake of essential fatty acids, vitamin B6, and vitamin C to treat dry eye (1). The rationale for this treatment was based on the biosynthesis of prostaglandin E1 (PGE1), which is necessary for aqueous tear secretion by the lacrimal glands.
 
• Linoleic Acid
  • Gamma Linolenic Acid
    • Di-hommo Gamma Linolenic Acid
      • PGE1
Methods:
In this pilot study, 17 patients were selected based on failure of tear secretion, objectively demonstrated (Schirmer Test), clinical exam, and the chronic need/use of lubricant drops. Patients received 2 X 500 mg capsules of evening Primrose oil (Efamol- 73% linoleic acid and 10% gamma linolenic acid), 50 mg vitamin B6 (pyridoxine) and 1 g vitamin C three times daily
Results:
Ten of the 17 patients showed substantial improvement of both symptoms and Schirmer test in 2-6 weeks. 3 additional patients reported improved symptoms though without demonstrating improved Schirmer. The authors conclude that this treatment approach is effective in many cases. They continue to work on dose optimization and plan further testing.

ScienceBased Health's HydroEye^® is formulated to provide nutritional components necessary to support tear film biosynthesis processes. By providing necessary essential fatty acid precursors and the vitamins acting as nutrient co-factors, HydroEye helps optimize tear production.
References

• Horrobin DF, Campbell A, McEwen CG: Treatment of the Sicca Syndrome and the Sjögren's Syndrome with E.F.A., Pyroxidine and Vitamin C. Prog Lipid Res 8(4): 253-4, 1981.
• Horrobin DF Campbell A. Sjögren's Syndrome and the Sicca Syndrome: the Role of Prostaglandin E1 Deficiency. Treatment with Essential Fatty Acids and Vitamin C. Medical Hypotheses. 6: 225-232 1980.
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How long does HydroEye take to work?
HydroEye offers long-lasting effectiveness with continued use. Results are typically experienced within 30-60 days.
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How does HydroEye differ from artificial tears and drops?
HydroEye is an oral formulation that works from the inside out to target the root causes of dry eye. Unlike topical products like drops and artificial tears, HydroEye does not require frequent re-application throughout the day. HydroEye provides uninterrupted relief within 30-60 days.
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Can HydroEye be used with other dry eye products?
HydroEye may be combined with artificial tears, punctum plugs or the medication Restasis®. Because HydroEye is an oral formulation that targets dry eye internally, it works by a complementary mode of action to these topical products. However, most users find that HydroEye provides adequate relief within 30-60 days.
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Can HydroEye be taken with Coumadin or other "blood thinning" medications?
A study published in 1994 reported that supplemental GLA lowered triglycerides, increased levels of "good" HDL cholesterol and prolonged the time it takes for blood platelets to clump together- factors which may contribute to cardiovascular health.
Platelets in the blood have a sticky surface which allows them, along with other substances, to form blood clots when bleeding occurs, a process called coagulation. Since platelets are involved in the process of forming clots, the GLA contained in HydroEye could theoretically increase the effects of anti-coagulant and anti-platelet medications such as Coumadin, Plavix or aspirin. If you are taking "blood thinning" medications, your physician can perform a Prothrombin time, INR, or bleeding time test to measure how long it takes blood to clot. This will ensure that HydroEye can safely be added to your current drug regimen.
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How does HydroEye differ from flaxseed and fish oils?
HydroEye provides the same omega-3s as flaxseed and fish oil. HydroEye now features EPA and DHA from highest-quality, USP verified fish oil. However, only HydroEye provides GLA (gamma linolenic acid). GLA effectively promotes the body's production of anti-inflammatory compounds. Both GLA and the omega-3 from fish oils have anti-inflammatory actions, but only GLA has been clinically shown to decrease dry eye symptoms.
Additionally, neither fish nor flaxseed oils contain other important nutrients that are included in HydroEye: vitamin B6 and magnesium to promote fatty acid metabolism, vitamin A to support the production of mucin in the tear film, and the antioxidant vitamin C to help fight the free radicals associated with inflammation.
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What’s the difference between the EE and TG forms of omega-3s?
Research suggests that the EE (Ethyl Ester) and TG (triglyceride) forms of omega fatty acids from fish oil are absorbed about the same when taken over several weeks or more. While some research measuring absorption over just a single day or less found the TG form to be better absorbed, differences disappear in studies that compared these forms over two weeks or more. SBH products contain the EE form, as the EE form has been used in nearly every clinical trial showing benefit for omega-3s from fish oil and is the choice for the National Eye Institute’s AREDS 2 trial now in progress. Learn more
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Why does it take more than just fish oil to combat dry eye?
Although discussion of fish omega forms has centered on their use for dry eye, research has not yet shown fish omegas to be a lead dry eye player. Instead, they are a useful adjunct to GLA, an omega that has demonstrated significant dry eye benefit in three clinical trials. When the fish omega EPA is paired with GLA, they reduce inflammation in a complementary fashion. HydroEye features GLA plus USP-verified fish oil that, along with other important nutrients, fights inflammation and supports all three layers of the tear film.
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