Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular...

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1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C – 2 nd Fl Presenter: Dr. Walt Whitley Walter Whitley, OD, MBA, FAAO serves as the Director of Optometric Services and Residency Program Supervisor at Virginia Eye Consultants in Norfolk, Virginia where his practice encompasses ocular surface disease, glaucoma, surgical co-management, clinical research and the supervision of an extensive referral network. He is a frequent lecturer and author on ocular disease, surgical comanagement and practice management topics. Dr. Whitley is the co-chief medical editor of CollaborativeEye and serves on the editorial boards for the Review of Optometry and Optometry Times. On the state level, Dr. Whitley is the current legislative chair for the Virginia Optometric Association and serves on the board of trustees. He was named the 2012 Young OD of the Year and the 2015 Keyperson of the Year for the Virginia Optometric Association. Course Description Proper diet and nutrition are plays a key role to maximize ocular health and preserve vision. This course will review the role certain foods and supplements and uses in common ocular conditions.

Transcript of Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular...

Page 1: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

1

Doctors of Optometry | Course Notes

OD9 – 1CE Ocular Nutrition Friend or Foe

Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C – 2nd Fl

Presenter: Dr. Walt Whitley Walter Whitley, OD, MBA, FAAO serves as the Director of Optometric Services and Residency Program Supervisor at Virginia Eye Consultants in Norfolk, Virginia where his practice encompasses ocular surface disease, glaucoma, surgical co-management, clinical research and the supervision of an extensive referral network. He is a frequent lecturer and author on ocular disease, surgical comanagement and practice management topics. Dr. Whitley is the co-chief medical editor of CollaborativeEye and serves on the editorial boards for the Review of Optometry and Optometry Times. On the state level, Dr. Whitley is the current legislative chair for the Virginia Optometric Association and serves on the board of trustees. He was named the 2012 Young OD of the Year and the 2015 Keyperson of the Year for the Virginia Optometric Association.

Course Description

Proper diet and nutrition are plays a key role to maximize ocular health and preserve vision. This course will review the role certain foods and supplements and uses in common ocular conditions.

Page 2: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

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Doctors of Optometry | Course Notes

NOTES:

Page 3: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

1

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those

know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term

multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013;

159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid, CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell

damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

– Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher

zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 4: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

2

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those

know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term

multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013;

159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell

damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

– Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher

zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 5: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

3

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those

know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term

multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013;

159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12 evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell

damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

– Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher

zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 6: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

4

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those

know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults: Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term

multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013;

159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell

damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

– Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher

zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management, exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 7: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

5

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those

know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term

multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013;

159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12 evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell

damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

– Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher

zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 8: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

6

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those

know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term

multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013;

159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell

damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

– Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher

zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 9: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

7

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those

know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013;

159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

–Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher

zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

1

2

1

2

3

4

5

6

7

8

9

10

11

12

13

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15

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Page 10: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

8

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term

multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013; 159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell

damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

– Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 11: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

9

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those

know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013;

159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

–Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher

zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 12: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

10

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term

multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013; 159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell

damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

– Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year DataNEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 13: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

11

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those

know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013;

159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell

damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

– Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher

zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 14: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

12

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term

multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013; 159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell

damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

– Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year DataNEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop

AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

[email protected]

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Page 15: Doctors of Optometry | Course Notes...1 Doctors of Optometry | Course Notes OD9 – 1CE Ocular Nutrition Friend or Foe Saturday, February 17, 2018 12:00 pm – 12:55 pm Plaza C –

7/14/2017

13

Ocular Nutrition: Friend or FoeCOPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO

Director of Optometric Services – Virginia Eye Consultants

Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Ocusoft

• Science Based Health

• Shire

• Sun Pharmaceuticals

• TearLab Corporation

• Tearscience

• Advanced Ocular Care

– Co-Chief Medical Editor

• Review of Optometry

– Contributing Editor

• Optometry Times

– Editorial Review Board

Questions We Should Ask???

• How would you describe your diet?

• What does a healthy diet look like for you?

• What did you have for breakfast?

• How many servings of fruits/vegetables do you have per day?

• How often do you eat fish?

• What medications are you taking?

Top 10 Vitamin Category SKUs

DON’T FORGET ABOUT….

Home Remedies, Herbal Supplements and Whatever MOM Told Me to Take

Herbal Medicine and Nutritional Supplements

Age-Related Eye Diseases

• More than 30 million people age 40 and older suffer vision loss in the U.S.

• Age-Related Macular Degeneration (AMD)

– Approximately 21 million Americans have AMD

– AMD cases have risen 25% since 2002, largest increase among major eye diseases

• Cataracts

–More than 24 million Americans have cataracts

– 400,000 new cases of cataract occur each year in the U.S.

Age-Related Eye Diseases

• Dry Eye Disease

– Approximately 29M Americans suffer from dry eye (1)

–Multifactorial – Contact lenses, digital devices, ocular surgery (2)

• Glaucoma

– It is estimated that over 3 million Americans have glaucoma but only half of those

know they have it. (3)

– Estimates put the total number of suspected cases of glaucoma at over 60 million

worldwide. (4)

Key Vitamins and Nutrients

Recommended Daily Value (FDA)

Benefits of Multivitamins

• Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults:

Scientific Review. Journal of the American Medical Association 287:3116-126, 2002.

• Webb AL et al. Update: effects of antioxidant and nonantioxidant vitamin

supplementation on immune function. Nutrition Reviews 65:181-217, 2007.

• Knecht P et al. Flavonoid intake and risk of chronic diseases. American Journal

Clinical Nutrition. 76:560-8, 2002.

• Holmquist C et al. Multivitamin supplements are inversely associated with risk of myocardial infarction in men and women. The Stockholm Heart Epidemiology

Program (SHEEP). Journal of Nutrition 133:2650-2654, 2003.

However…

• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an

updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.

• Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.

• Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and

minerals after myocardial infarction. A randomized trial. Ann Intern Med. 2013;

159:797-804.

Nutrients for Healthy Eyes

• 500 mg/day Vitamin C

• 400 IU/day Vitamin E

• 25 or 80 mg Zinc / 2 mg Copper per day

• 10 mg Lutein / 2 mg Zeaxanthin per day

• 350 mg DHA / 650 mg EPA per day

Vitamin C

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 75 – 90 mg/day (DRI)

– 500 mg/day (eye health)

• Where can I get it in my diet?

– Citrus fruits and juices

Vitamin E

• Why is it important?

– Body unable to synthesize

– Antioxidant capability

• How much do I need each day?

– 22 IU/day (DRI)

– 400 IU/day (Eye Health)

• Where can I get it in my diet?

– Nuts, fortified cereals, sweet potatoes

Zinc

• Why is it important?

– Essential trace element

• How much do I need each day?

– 8-11 mg zinc/day (DRI)

– 40 – 80 mg zinc/day (Eye Health)

• Where can I get it in my diet?

– Red meat, poultry, mixed nuts

• Copper

– High zinc may cause copper deficiency

– 2 mg included in AREDS study

How Much Do I Need Each Day?

• 10 mg/day lutein

• 2 mg/day zeaxanthin

• Dietary Guidelines for Americans*

– Equivalent to 4 - 8 mg lutein & zeaxanthin / day

–< 4% Americans meet guidelines

– U.S. average: 1 – 2.5 mg/day

Internal Pair of Sunglasses

Essential Fatty Acids - DHA/EPA

• Why are they important?

– Important role in many bodily organs/systems

• How much do I need each day?

– 350 mg DHA / 650 mg EPA per day

• Where can I get them in my diet?

– Flax, fleshy fish like tuna or salmon

Don’t Forget Your Vitamins

• Vitamin A

– Dairy, fish, meat, eggs, leafy green vegetables, orange and yellow vegetables

– Rhodopsin, support function of mucus membrane, bones, soft tissues, teeth

• Vitamin K

– Leafy green vegetables, vegetable oil, some fruit

– Blood clotting

And All the “B”s

• B1 (Thiamine)

– Energy metabolism

• B2 (Riboflavin)

– Energy production, amino acid production, cofactor in antioxidant production

• B3 (Niacin)

– Function of skin, nerves, digestive system, cholesterol levels

• B5 (Pantothenic Acid)

– Cell growth, RBC production, hormones

• B6 (Pyridoxine)

– RBC production, brain function, immune, decrease homocysteine

• B7 (Biotin)

– Cell growth, fatty acid production, fat metabolism, steady blood sugar level

• B9 (Folic Acid)

– RBC production, prevent anemia, fetal development

• B12 (Cobalamin)

–Myelin synthesis/repair, DNA/RNA and RBC production, iron function

What is in your Multivitamin/Supplement?

• Independent chemical analysis websites

– Labdoor.com

– ConsumerLab.com

–MultivitaminGuide.com

• Independent certification labels:

– Natural Products Association (NPA Certified)

– U.S. Pharmacopeial Convention (USP Verified)

– NSF (NSF Certified)

Testing Summary

• Out of top 75 best-selling multivitamin scored by Labdoor.com

1. Label accuracy

2. Product purity

3. Nutritional value

4. Ingredient safety

5. Projected efficacy

Testing Summary

• Tested values of vitamin label claims were off by 22.6% and minerals by 29.2%

–Most common was an overstated amount of Vitamin A and C

• Gummy and chewable MV compared to standard MV had 54% less vitamin content and 70% less mineral content

Recommending the Right Supplements

• In-Office product line expansion

– Patient benefits

– Practice benefits

• OTC

– CL (Consumer Lab)

– GMP (Good Manufacturing Processes)

– NSF International (NSF)

– USP (U.S. Pharmacopeial Convention)

Retail Therapy

Improving the Screening, Diagnosis, and Management of Dry Eye Disease

Consensus on Baseline Management

1. For all patients:

A. Ocular lubrication

B. Lid hygiene

C. Nutrition

2. Topical anti-inflammatories

Dry Eye International Task Force:

Therapeutic Recommendations

Oral Medications for Dry Eye

• Nutritional supplements

– 1,000 mg BID of Omega-3 Fish Oil

• Lovaza (Rx fish oils)

– 4g per day po

– Indicated as an adjunct to diet to reduce triglyceride levels in adult patients with

severe hypertriglyceridemia

• Oral pilocarpine

– Salagen®: 5 mg qid for dry mouth

– Evoxac®: 30 mg tid for dry mouth

Nutraceuticals and OSD

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

Anti-inflammatory Fatty Acids

GLA Specificity to Dry Eye: lacrimal production

• GLA is precursor of an anti-inflammatory prostaglandin, PGE1

• PGE1 found in tears, lacrimal gland & conjunctiva (1,2)

Cool Cofactors

• To convert GLA to PGE1 (the key inflammation fighting step), you also need B6,

magnesium and vitamin C

Effect of Oral Re-Esterified Omega-3 Nutritional Supplementation on Dry-Eye Disease: Double-Masked Randomized Placebo-Controlled Study

• This was a multicenter, prospective, interventional, placebo controlled, double

masked, randomized trial.

• 105 patients with dry eye disease

– Four capsules (2 gm) once a day containing 1680mg EPA and 560mg DHA (PRN

Dry Eye Omega Benefits) for 3 months or four capsules of placebo.

– All patients underwent a screening, baseline, 6 week and 12 weeks visit.

–On each visit patients were tested for tear osmolarity, MMP-9, fluorescein corneal staining, Schirmer’s testing, and OSDI. On the screening exam and week 12

evaluation patients had their omega index tested.

• This study demonstrated that oral consumption of re-esterified omega-3 fatty acids (1680 mg EPA and 560 mg DHA once daily for 12 weeks) is an effective

treatment of dry eye disease and results in a statistically significant improvement in tear osmolarity, OSDI, tear break up time and omega index levels.

Nutrition and Glaucoma

Neuroprotection

• Despite lowering eye pressure (IOP), some glaucoma patients will suffer increasing damage

• Researchers therefore now looking beyond just IOP

• Neuroprotection aims to protect neurons along the entire visual pathway, chiefly retinal nerve cells (retinal ganglion cells) (RGCs)

Examples of Targets:

Oxidative Stress – High metabolic activity of retinal tissues make RGCs especially vulnerable to oxidative stress (especially in mitochondria)

Antioxidants: Vitamins C, E, NAC (glutathione precursor), alpha lipoic acid,

CoQ10 (protects mitochondria in RGC axons)

Mitochondia – Key Battleground for Oxidative Stress & Cell Death

• Oxidative compounds (free radicals) are bi-product of energy production in

mitochondria – cell’s energy factories

• Excess free radical production (oxidative stress) in mitochondria lead to to

mitochondrial DNA mutations, release of substances that help trigger cell death.

• CoQ10 is key antioxidant in mitochondria, found to protect against cell death.

Selected Nutrients for Glaucoma

Glaucoma Considerations

• Vitamin E clinically demonstrates neuroprotection1

• Antioxidants protect meshwork cells in experimental study2

• Ginkgo Biloba clinically shown to improve visual field indices3

• Lower levels of EPA and DHA seen in glaucoma patients4

Ginko Biloba

• Source of protective flavonoids and compounds that reduce clumping of blood

platelets

• Experimentally, Ginkgo biloba scavenges nitric oxide radicals implicated in nerve cell damage, and prevents neurotoxicity from excess glutamate

• Found to increase ocular blood flow in healthy people and to improve visual field in those with normal IOP

Anthocyanins

• Stabilize collagen fibers and promote collagen biosynthesis

• Decrease capillary permeability and fragility, with inhibition of platelet aggregation

• Prevent pro-inflammatory compounds

• Lower blood glucose levels

• Anthocynanins are found in berries, red onions, kidney beans, pomegranates, grapes (including wine), tomatoes, acai, bilberry, chokeberry, elderberry, and tart cherries

Glaucoma

• A recent study by the Association for Research in Vision and Ophthalmology (ARVO)

revealed that the herbal supplement baicalein significantly lowers eye pressure and may act as an all-natural treatment for glaucoma. When animals were treated with

baicalein, a type of flavonoid, their eye pressure was reduced by improving the rate at which fluid drained from the eye. The effect increased when baicalein was

administered under nighttime conditions.

Harmful or Helpful?

Nutrition and Cataracts

Cataracts and Nutrients

• High levels of antioxidant Vitamins C and E may decrease the development or

progression of cataracts

– The Nutrition and Vision Project

– Second National Health and Nutrition Examination Survey

– Nurses’ Health Study

– The Roche European American Cataract Trial

– Longitudinal Study of Cataract

– Beaver Dam Eye Study five year follow up

Cataracts and Nutrients

• Lutein and zeaxanthin possibly reduce cataract progression

– Health Professional’s Follow-Up Study

– Beaver Dam Eye Study five year follow-up

– Recent study in England

Cataracts

• AREDS2 found that lutein and zeaxanthin may play a role in cataract prevention1

• Increased levels of lutein and zeaxanthin have been shown to have a significant

correlation with decreased risk of cataracts2

Can We Prevent Cataracts?

• Annual examinations

• Rx with anti-glare / ARC

• UV Protection

• Smoking cessation

• Targeted nutritional support??

Macular Degeneration

ARMD Statistics

• Prevalence

– 54% = White

– 14% = Hispanic

– 4% = Black

• Bilateral

– 50% of unilateral advanced AMD developed advanced AMD in 5 years in the fellow

eye

• Risk Factors

– Age

– Race

– Heredity

– Smoking

– HTN

–Diet

– Pseudophakia

Categories in AREDS

1. Category 1

• <5 small drusen

• >20/30 OU

2. Category 2

• Multiple small drusen

• Single intermediate drusen

• Pigment abnormalities

• >20/30 OU

3. Category 3

• No advanced AMD in both eye

• >20/30 in study eye

• Extensive intermediate drusen

• One or more large drusen

• GA not involving center of macula

4. Category 4

• No advanced AMD in study eye

• >20/30 in study eye

• Advanced AMD, VA <20/30 in fellow eye

AREDS

• Daily supplement dosage

– Beta-carotene – 15 mg

– Vitamin C – 500 mg

– Vitamin E – 400 IU

– Zinc – 80 mg/Copper – 2 mg

• Conclusions

– AMD is a nutrition responsive disorder

– 25% decreased risk of progression of advanced AMD

– 19% reduction of visual acuity loss

– 6% absolute risk reduction in high risk group

Results

• Secondary Outcomes

– Neovascular AMD at baseline (nonstudy eye) had reduced risk of losing 15 letters or more in ALL ARMS

– Antioxidants + zinc vs placebo reduced risk the greatest of progressing to wet AMD

– Categories 3 and 4 had reduced risk of GA in ALL ARMS

– No evidence of treatment benefit (i.e. delaying the progression of AMD) in participants who began the study in Category 2

AREDS 10-year Data

NEI Conclusions and Recommendations

• Subjects (AREDS category 2, 3, and 4) originally assigned to the antioxidants + Zn

arm showed continued reduced odds of progression to advanced AMD, especially NV

AMD, 5 years post study

• The NEI continues to recommend AREDS supplementation in persons with

moderate to advanced AMD (category 3 and 4)

• Much of the benefit of the AREDS formulation is driven by efficacy in decreasing the

development of NV AMD and not CGA

– However, the recommendation continues to be to consider AREDS supplementation for all category 3 and 4 patients

• The rate of conversion to NV AMD in patients with CGA may be as high as 40% in 10 years (AREDS data, submitted for publication)

– The simultaneous occurrence of both forms of advanced AMD is common.

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if:

• Extensive intermediate drusen

• 1 or more large drusen

• Non-central geographic atrophy

• Advanced AMD

• Vision loss due to AMD in 1 eye

AND

• Non-smoker

AREDS2

Study Objectives

• Effects of adding high doses of macular xanthophylls and/or OM-3 FAs to AREDS on AMD progression and cataract

– Effects of these supplements on moderate vision loss*

• Impact of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD development and progression

AREDS2: Summary of Key Findings

• In the primary analysis, adding L+Z and/OM-3 to AREDS-like supplements did not

further reduce risk of progression to advanced AMD as defined by the primary

endpoint

• However, in the secondary analyses, beneficial effects were observed in patients

who received L+Z:

–Overall, L+Z supplementation reduced the risk of progression by ~ 10% versus no supplementation with L+Z

– There was a 26% reduction in risk for progression in those given L+Z who had the lowest dietary intake of L and Z

– Supplementation with an AREDS supplement containing L+Z without BC (vs. BC

without L+Z) reduced risk of progression by 18%

AREDS2: Summary of Key Findings

• While the study did not test for equivalency between high and low dose Zn and

between no beta carotene and beta carotene,

– An increased risk of lung cancer in former smokers* was associated with beta-carotene

– No differences were observed in risk reduction or adverse events for low (25 mg) zinc vs. high (80 mg) zinc

• There is not sufficient evidence to change the high zinc recommendation that

was confirmed in the original AREDS

• Based on the data from AREDS2, the NEI recommends an adjusted AREDS formula

for AREDS categories 3 and 4

49% Derive More Benefit from Treatment other than AREDS

AREDS 2 Drawbacks

• Not placebo controlled like AREDS 1 (AREDS2 tested formula variations vs each

other) – not gold standard

• Too many research questions = diluted / less conclusive findings

• Had to meet very steep threshold for significance (minimum 25% greater benefit then AREDS1)

• High vs low Zinc levels inconclusive (but trend towards more benefit with higher

zinc)

• Zinc-free / genetic testing controversy further muddied waters

• Meso-zeaxanthin also confuses

• YET: Still provided some useful info

AREDS2: Recommendation

• NEI Recommended AREDS2 formulation

– Vitamin C (500 mg)

– Vitamin E (400 IU)

– Beta Carotene (15 mg)

– Lutein (10 mg)/Zeaxanthin (2 mg)

– Zinc (80 mg zinc oxide)

– Copper (2 mg cupric oxide)

–Omega 3 fatty acids (DHA/EPA)

Dry ARMD Treatments

• Prevention

– Stop smoking, vitamins B and D, fish oil, UV protection, weight management,

exercise and diet

• Early

– Take home Amsler grids

• Intermediate

– AREDS2: AREDS without beta carotene for smokers

• Advanced

• AREDS 2

– Low vision therapy

Age-Related Eye Diseases

• Surgical / Injections

– Thermal laser

– Photodynamic therapy

– Anti-VEGF

The Most Important AMD Nutrition Study You’ve Never Heard Of

WAFACS (Women’s Antioxidant Folic Acid & Cardiovascular Study)

• NEI-Funded, Harvard Clinical Trial (randomized, placebo-controlled, double-blind)

• Female Health Professionals with / at risk for CVD

• Larger, Longer then AREDS (n=5,400; 7yrs avg follow up)

• AMD was secondary endpoint

• Results: women taking high dose B6, B12, folate were 34% less likely to develop AMD and 40% less likely to have AMD-related vision loss than control group

WAFACS

• B6, B12, Folate:

• WAFACS used high doses – some prescription only or not higher then generally recommended

• In response, SBH raised B-vitamin levels in products (within reasonable dose ranges)

• Good news: Blue Mountains Eye Study finds that even far more modest levels of

these 3 Bs linked to AMD risk

Nutrition and Presbyopia

Presbyopia

• Kajita et al., 2009. The effects of a dietary supplement containing astaxanthin on the accommodation functions of the eye in middle-aged and older people. Medical

Consultation & New Remedies, 46 (3):89-92.

– Suggests that astaxanthin supplementation may help slow down the progression

of presbyopia or improve near vision of people above 40 years of age

– The improvement of accommodation function was 12.5% in both eyes (p<0.01) and subjects generally claimed reduction of eye strain and better near vision

THANK YOU

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