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Nutraceuticals and Dry Eye
Jeffrey P. Gilbard, MD
Dennis Pardo, OD
12 Alfred Street, Suite 200
Woburn, MA 01801
781-932-8327
Abstract The American diet is deficient in omega-3 and this has now been linked to an increased risk of
dry eye in population-based studies. Omega-3s are important in decreasing inflammation in the lacrimal
gland and the meibomian glands, protecting the lacrimal gland and promoting tear secretion, giving them
an important role in dry-eye treatment
.
Learning Objectives
At the conclusion of this presentation the participant should be able to:
1.
2.
3.
4.
Describe how decreased tear production or increased tear evaporation causes dry eye surface disease.
Discuss how the long chain omega-3s known as “EPA” decreases inflammation.
Discuss how DHA is proposed to improve lacrimal gland function in Sjögren’s syndrome.
Describe the population-based studies linking a deficiency of dietary omega-3s with dry eye.
Outline
1) How we Know Elevated Tear Osmolarity Causes Dry Eye
a)
Pathology explained by increased osmolarity
b) Decrease in conjunctival goblet cells and glycogen proportional to increases in tear osmolarity
c)
Increases in tear film osmolarity cause increased expression of inflammatory cytokines on ocular
surface
2) Mechanism for Increased Tear Osmolarity and Dry-Eye Disease
a)
Decreased tear secretion
i)
Lacrimal gland dysfunction—Autoimmune disease (keratoconjunctivitis sicca), cicatricial
damage to lachrymal gland excretory ducts, surgical removal of lachrymal gland
ii) Decreased corneal sensation—Vth nerve deficits, corneal or limbal incisions, LASIK, herpes,
diabetes, contact lens wear
b) Increased tear film evaporation
i)
Large palpebral fissure width—thyroid eye disease, blepharoplasty or ptosis surgery, larger
eyes
ii) Meibomian gland dysfunction secondary to meibomitis
3) Omega-3s and Dry Eye
a)
Omega-3s and Omega-6s
i)
Essential fatty acids are fats your body needs but can’t produce. It’s essential they be eaten.
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A 2003 Approach to Treating the Dry Eye
ii) Omega-3:omega-6 ratio in American diet is about 1:10. Optimum ratio for good health is 1:2.
iii) We get omega-6s from vegetable oils, vegetable shortening, dairy products, & beef.
iv) Omega-3:omega-6 American diet too light in omega-3’s from dark oily cold-water fish, &
flaxseed.
b) Tumor Necrosis Factor-a—a pro-inflammatory cytokine
i)
TNF-a increased in lacrimal gland in Sjögren’s syndrome
ii) TNF-a increases apoptosis and auto antibodies in lacrimal gland in Sjögren’s syndrome
iii) TNF-a decreases neural synapse transmission in the lacrimal gland and decreases tear
production in Sjögren’s syndrome
iv) Increased tear film osmolarity in dry eye increases expression of TNF-a on ocular surface.
c)
How Omega-3s Thwart TNF-a
i)
The long-chain omega-3 called EPA blocks the gene transcription of TNF-a.
ii) DHA and vitamin E work synergistically to make cells more resistant to damage from TNF-a
iii) DHA improves neural synapse function
d) How Omega-3s Additionally Decrease Inflammation
i)
Suppresses meibomitis by generating anti-inflammatory ecosanoids, decreasing proinflammatory ecosanoids, and blocking pro-inflammatory cytokine formation at the gene
transcription level.
ii) Promote the formation of anti-inflammatory PGE1.
e)
How Omega-3s Promote Tear Production
i)
f)
PGE1 stimulates tear production.
Effect of Omega-3s on the Tear Film Oil Layer
i)
Augment the oil layer by providing the essential fatty acids needed to make healthy meibum.
ii) Omega 3s effect the lipid profiles of meibomian gland secretions in Sjögren’s patients.
(HPLC/mass spectrometry studies) (Sullivan BD et al 2002)
iii) Clinical reports have observed clearer and thinner oils with omega-3 (flaxseed oil) treatment.
(Boerner CF 2000)
g) Previous Studies of Omega-3s and Dry Eye
i)
Sjögren's patients have a lower dietary intake of Omega-3s, including EPA & DHA, than
matched controls
ii) Severity of dry eye in Sjögren's syndrome is inversely proportional to membrane and serum
levels of DHA
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Dry Eye: Natural History, Diagnosis and Treatment
h) Dietary Omega-3 Fatty Acid Intake & Risk of Dry Eye
i)
Recent study of 32,470 female health professionals found that the higher the dietary omega-3
fatty acid intake, the lower the incidence of clinically diagnosed dry eye (Trivedi et al.
ARVO, 2003,).
ii) 2-4 servings/wk of tuna fish reduced the risk by 18%, compared to <2 servings/wk
iii) 5-6 servings/wk of tuna fish reduced the risk by 66%, compared to <2 servings/wk
iv) The greater the omega-3 intake the lower the risk for dry eye. The risk decreases 30% for
each additional gram of dietary omega-3 per day.
v) Omega-6s negate the beneficial effects of omega-3s. The higher the omega-6: omega-3 ratio,
the greater the risk for dry eye.
vi) Growing body of knowledge suggests that omega-3 fatty acids may play a causative role in
the pathogenesis of dry eye syndrome
i)
Omega-3 Supplement with Flaxseed/Fish oil (EPA & DHA) & Vitamin E
i)
Flaxseed oil increases total omega-3 intake; improves omega-6:omega-3 ratio.
ii) Fish oil provides pre-assembled long-chain omega-3s (EPA & DHA)
iii) 1.5 gms of fish oil, 1 gm of flaxseed oil and 200 IU of Vitamin E in the morning. Double the
dose in patients with rheumatoid arthritis.
iv) Takes about 4 to 8 weeks to work
v) For patients with meibomitis, use with or without doxycycline 50mg a day. Use of omega-3s
enables taper of doxycycline without return of symptoms.
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A 2003 Approach to Treating the Dry Eye
vi) Anectodal experience positive, prospective studies underway.
4) The natural history of dry-eye disease dictates the sensitivity of diagnostic tests and the efficacy of
treatment.
5) Reading References
a)
Oxholm P, Asmussen K, Wiik A, Horrobin DF: Essential fatty acid status in cell membranes and
plasma of patients with primary Sjögren’s syndrome. Correlations to clinical and immunologic
variables using a new model for classification and assessment of disease manifestations.
Prostaglandins Leukot Essent Fatty Acids 59(4):239-245, 1998.
b) Sullivan BD, Cermak JM, Sullivan RM, Papas AS, Evans JE, Dana MR, Sullivan DA:
Correlations between nutrient intake and the polar lipid profiles of meibomian gland secretions in
women with Sjögren’s syndrome. In Lacrimal Gland, Tear Film, and Dry Eye Syndrome, D.
Sullivan et al. eds, Kluwer Academic/Plenum Publishers, 2002, pp. 441-447.
c)
Trivedi KA, Dana MR, Gilbard JP, Buring JE, Schaumberg DA: Dietary omega-3 fatty acid intake
and risk of clinically diagnosed dry eye syndrome in women. ARVO, 2003.
d) Zejin Z, Stevenson D, Schechter JE, Mircheff AK, Crow RW, Atkinson R, Ritter T, Bose S,
Trousdale MD: Tumor necrosis factor inhibitor gene expression suppresses lacrimal gland
immunopathology in a rabbit model of autoimmune dacryoadenitis. Cornea 22(4):343-351, 2003.
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e)
Zoukhri D, Kublen CL: Impaired neurotransmitter release from lacrimal and salivary gland nerves
of a murine model of Sjögren’s syndrome. Invest Ophthalmol Vis Sci 42(5):925-932, 2001.
f)
Zoukhri D, Hodges RR, Byon D, Kublin CL: Role of proinflammatory cytokines in the impaired
lacrimation associated with autoimmune xerophthalmia. Invest Ophthalmol Vis Sci 43(5):14291436, 2002.