Ocular Nutrition: Friend Or Foe COPE: 48735-OP

4/7/2017

Ocular Nutrition: Friend or Foe COPE: 48735-OP

Walter O. Whitley, OD, MBA, FAAO Director of Optometric Services – Virginia Eye Consultants Residency Program Supervisor – Pennsylvania College of Optometry

Disclosures Walter O. Whitley, OD, MBA, FAAO has received consulting fees, honorarium or research funding from: • Alcon • Advanced Ocular Care • Allergan – Co-Chief Medical Editor • Bausch and Lomb • Review of Optometry – Contributing Editor • Biotissue • Optometry Times • Beaver-Visitec – Editorial Review Board • Ocusoft • Science Based Health • Shire • TearLab Corporation

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?

Accessed from http://www.aoa.org/news/clinical-eye-care/6-nutrition-questions-you-should-be-asking-patient. -?

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Top 10 Vitamin Category SKUs

Rank SKU Description $ Sales (000s)

1 Mega Red Omega 3 60ct $34,301 2 Lipozene 30ct $32,593 3 Align Probiotic 28 ct $28,421 4 Centrum Silver Ultra Women’s 100ct $27,357 5 Centrum Silver 125ct $27,234 6 Airborne 10ct $26,578 7 Ocuvite Adult 50+ 50ct $26,133 8 PreserVision AREDS Soft Gels 120ct $25,802 9 Align Probiotic 42ct $25,008 10 Phillips Colon Health 30ct $23,588

Source: Nielsen XAOC 52 weeks ending May 11, 2013

DON’T FORGET ABOUT

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

Herbal Medicine and Nutritional Supplements

Fraunfelder FW. Ocular side effects from herbal medicines and nutritional supplements. Am J Ophthalmol. 2004 Oct;138(4):639-47

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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 22 million Americans have cataracts – 400,000 new cases of cataract occur each year in the U.S.

Prevent Blindness America/National Eye Institute 2008 “Vision Problems in the US” W. Reed Moran, Spotlight Health, With medical adviser Stephen A. Shoop, M.D., USA Today, Feb. 2001

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)

Sources: (1) Paulsen AJ, Cruickshanks KJ, Fischer ME, et al. Dry eye in the beaver dam offstrping study: prevalence, risk factors, and health-related quality of life. Am J Ophthalmol. 2014;157(4):799-806. (2) Dry Eye Workshop. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf. 2007;5(2):93-107. (3) The Eye Diseases Prevalence Research Group, Arch Ophthalmol. 2004; Prevent Blindness America; (4) Quigley and Broman "Number of people with glaucoma worldwide in 2010 and 2020", 2006;

Key Vitamins and Nutrients

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Recommended Daily Value (FDA)

Nutrient DV Nutrient DV Nutrient DV

Potassium 3500mg Niacin 20mg Selenium 70μg Vitamin A 5000 IU Vitamin B6 2mg Copper 2mg Vitamin C 60mg Folate 400μg Manganese 2mg Calcium 1000mg Vitamin B12 6μg Chromium 120μg Iron 18mg Biotin 300μg Molybdenum 75μg Vitamin D 400 IU Pantotheric Acid 10mg Chloride 3400mg Vitamin E 30 IU Phosphorus 1000mg Thiamin 1.5mg Vitamin K 80μg Iodine 150μg

Riboflavin 1.7mg Magnesium 400mg Zinc 15mg

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.

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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

Jacob, R. A. and G. Sotoudeh (2002). "Vitamin C function and status in chronic disease." Nutrition in clinical care 5(2): 66-74. (2001). "A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age- related macular degeneration and vision loss: AREDS report no. 8." Arch Ophthalmol 119(10): 1417-36. Chiu, C. J. and A. Taylor (2007). "Nutritional antioxidants and age-related cataract and maculopathy." Experimental eye research 84(2): 229-45.

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

(2001). "A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age- related macular degeneration and vision loss: AREDS report no. 8." Arch Ophthalmol 119(10): 1417-36. Chiu, C. J. and A. Taylor (2007). "Nutritional antioxidants and age-related cataract and maculopathy." Experimental eye research 84(2): 229-45. Chew, E. (2007). “Age-related eye disease study 2 protocol.” National Eye Institute Protocol 07-EI-0025.

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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

(2001). "A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age- related macular degeneration and vision loss: AREDS report no. 8." Arch Ophthalmol 119(10): 1417-36. Chew, E. (2007). “Age-related eye disease study 2 protocol.” National Eye Institute Protocol 07-EI-0025. Grahn, B. H., P. G. Paterson, et al. (2001). "Zinc and the eye." Journal of the American College of Nutrition 20(2 Suppl): 106-1http://eathealthylivefit.com/wp-content/uploads/2014/05/Foods-Minerals- Zinc-EatHealthyLiveFit_com-300x206.png8.

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 *9 servings of fruits and vegetables every day; recommendation based on the reference 2,000 calorie diet.

HHS/USDA. Dietary Guidelines for Americans 2005. http://www.healthierus.gov/dietaryguidelines/CDC. National Health and Nutrition Examination Survey Data 2001-2002. http://www.cdc.gov/nchs/about/major/nhanes/nhanes01-02.htm Richer, S., W. Stiles, et al. (2004). "Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age- related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial)." Optometry75(4): 216-30. Stringham, J. M. and B. Hammond (2008). "Macular Pigment and Visual Performance Under Glare Conditions." Optometry & Vision Science 85(2): 82-88. Chew, E. (2007). “Age-related eye disease study 2 protocol.” National Eye Institute Protocol 07-EI-0025.

Internal Pair of Sunglasses

Carotenoids such as lutein and Good nutrition zeaxanthin filter helps reduce the blue light to block risk of chronic eye production of free diseases such as radicals macular degeneration and The sun emits may improve photo oxidizing visual function (UV) rays that are harmful to Sunglasses the eyes reduce free radicals

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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

Fliesler, et al. Prog Lipid Res (1983) 22:79-131 Connor, et al. Nutr Rev (1992) 50:21-29 Cho, et al. Am. J. Clin. Nutr. (2001) 73:209-218 Birch, et al. Ped. Res. (1998) 42: 201-209. Chew, E. (2007). “Age-related eye disease study 2 protocol.” National Eye Institute Protocol 07-EI-0025. http://www.ebestacnetreatment.com/wp-content/uploads/2012/07/essential-fatty-acids.jpg

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) • B6 (Pyridoxine) – Energy metabolism – RBC production, brain function, immune, • B2 (Riboflavin) decrease homocysteine – Energy production, amino acid production, • B7 (Biotin) cofactor in antioxidant production – Cell growth, fatty acid production, fat • B3 (Niacin) metabolism, steady blood sugar level – Function of skin, nerves, digestive system, • B9 (Folic Acid) cholesterol levels – RBC production, prevent anemia, fetal • B5 (Pantothenic Acid) development – Cell growth, RBC production, hormones • B12 (Cobalamin) – Myelin synthesis/repair, DNA/RNA and RBC production, iron function

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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

https://labdoor.com/rankings/multivitamins

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

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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

Recommendations

PROGRAM CHAIRS: Marc Bloomenstein, OD, FAAO Derek Cunningham, OD, FAAO Ian Benjamin Gaddie, OD, FAAO Paul Karpecki, OD, FAAO Scot Morris, OD, FAAO Kelly Nichols, OD, PhD, FAAO

EXPERT CONTRIBUTORS: Improving the Barbara Caffery, OD, PhD, FAAO Doug Devries, OD Mark Dunbar, OD, FAAO S. Barry Eiden, OD, FAAO Art Epstein, OD, FAAO, FABCO, FBCLA, DPNAP Screening, Diagnosis, David Geffen, OD, FAAO Scott Hauswirth, OD Milton Hom, OD, FAAO Lyndon Jones, PhD, FCOptom, FAAO Al Kabat, OD, FAAO and Management of Tom Kislan, OD Blair Lonsberry, OD, MEd, FAAO, ABO Katherine Mastrota, OD, FAAO Ron Melton, OD, FAAO Jason Miller, OD, FAAO Dry Eye Disease Jason Nichols, OD, PhD, FAAO Dominick Opitz, OD, FAAO Jim Owen, OD, FAAO Lisa Prokopich, OD Thomas Quinn, OD, FAAO John Rumpakis, OD, MBA Jack Schaeffer, OD, FAAO Joseph Shovlin, OD, FAAO Kirk Smick, OD Randall Thomas, OD, FAAO William Townsend, OD Gina Wesley, OD, FAAO Walter Whitley, OD, FAAO Recommendations from the Dry Eye Summit 2014

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Consensus on Baseline Management

1. For all patients: A. Ocular lubrication B. Lid hygiene C. Nutrition 2. Topical anti-inflammatories

Recommendations from the Dry Eye Summit 2014

Dry Eye International Task Force: Therapeutic Recommendations Patient education Level 1 Environmental modifications Control systemic medications Preserved tears Allergy control If no improvement, add level 2 treatments Unpreserved tears Gels/nighttime ointments Level 2 Nutritional support Topical corticosteroids Cyclosporine Secretagogues If no improvement, add level 3 treatments Tetracyclines Level 3 Punctal plugs (once inflammation is controlled) If no improvement, add level 4 treatments Systemic antiinflammatory therapy Level 4 Acetylcysteine Moisture goggles Surgery (punctal cautery)

Adapted with permission from O’Brien TP. Refract Eyecare. 2005;9(suppl):7-11.

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

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Nutraceuticals and OSD

Sheppard JD, Pflugfelder SC, et al. Long-term supplementation with n-6 and n-3 PUFAs improves moderate-to-severe Keratoconjunctivitis Sicca: A randomized double-blind clinical trial. Cornea 32 :1297-1304, 2013.

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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.

Donnenfeld ED, Holland, EJ, Bucci FA, et. Al. 2015

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Slide Courtesy of Milton Hom, OD, FAAO

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)

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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)

Countering toxic compounds– High glutamate levels can be toxic to neurons Anti-Glutamate: Taurine & alpha lipoic counter effects

Improving Blood flow—Low blood flow to optic nerve damages nerve cells (RGCs) Blood Flow Support: ginkgo biloba, bilberry & grape seed extracts, vitamin C, magnesium & B-vitamins (lower Hcy)

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

Quercetin

Vitamin C FlavonoidsCoQ10NAC N-Acetyl Cysteine (fromQUERCETIN bilberry,Ginkgo grape seed extracts) Experimentally,Supports mitochondrial protects VitAndExperimentally,AlphaPromotesC:VitAntikey muchE:-inflammatory protectsprotectorLipoic blood more protects fatty flow, Acidagainst … functionagainst (cell’s nitric energyoxide nerveantioxidantshelps(notExperimentally,compounds oxidativecells protectall antioxidantsfrom that nervestress, oxid in support helpscell. -cells stress / radicals.factories). Supplies Mitochondrial building injury,concentratedmembranes,bloodfromprotectbenefits may oxidative vessels. neurons protect shown) inespec Clinical aqueousstress. fromagainst. in dysfunctionblock for glutathione is key factor – the in excessretina;humorClinicalfindings:glutamate glutamate, recharges& findings: inside increased toxicity nerve improvedvitaminwhich blood cells can C Vitamin E deathbody’s of retinal main built ganglion-in Flavonoids flowcausefield & decreasednerve damage damage. inIOP in (from bilberry, grape seed normotensionocularcellsantioxidant in hypertension glaucoma.glaucoma. extracts)

Alpha Lipoic Ginkgo biloba

CoQ10

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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

1. Engin KN et al. Clinical evaluation of the neuroprotective effect of alpha tocopherol in glaucomatous damage. European Journal Ophthalmology 17:528-33, 2007. 2. Yuan He et al. Mitochondrial Complex I defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: Protection by Antioxidants. Investigative Ophthalmology Visual Science 49:1147-58, 2008. 3. Quaranta L et al. Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology 110:359-62 2003. 4. Ren H et al. Primary open-angle glaucoma patients have reduced levels of blood docosahexaenoic and eicosapentaenoic acids. Prostaglandins Leukotrienes Essential Fatty Acids. 74:157-63, 2006.

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

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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.

Posted: 5/6/2015

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Harmful or Helpful?

• Alcohol – Weak evidence indicates a dose-related IOP reduction through temporary osmotic effect – Large quantities of beer or water increase IOP significantly – Possible neuro-protective effect of red wine • Marijuana – Active ingredient delt-9-tetrahydrocannabinoid reduce aqueous humor production • However, short term and must smoke every 3 hours for 24 hour IOP control • Caffeine – Antioxidative effect

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

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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

1. AREDS2 Research Group. “Lutein/Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration. The Age-Related Eye Disease Study 2 (AREDS2) Controlled Randomized Clinical Trial.” JAMA, published online May 5, 2013. 2. Karppi J, et al. Plasma lutein and zeaxanthin and the risk of age-related nuclear cataract among the elderly Finnish population. Br J Nutr published ahead of print, 2012.

Can We Prevent Cataracts?

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Macular Degeneration

Advanced AMD: † Any AMD : 1.7M (2.6%) 10M (15.4%)

Wet AMD: Intermediate AMD: *16.4% of the 1.2Mintermediate* (1.85%) 7.3M (11.2%) AMD Group

Caucasians >55: 65M

†54% of patients diagnosed with AMD are Caucasian Friedman et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004 Apr;122(4):564-72. U.S. Census Buereau (NC-EST2006-04-WA)

ARMD Statistics

• Prevalence • Risk Factors – 54% = White – Age – 14% = Hispanic – Race – 4% = Black – Heredity • Bilateral – Smoking – 50% of unilateral advanced AMD – HTN developed advanced AMD in 5 – Diet years in the fellow eye – Pseudophakia

Categories in AREDS

1. Category 1 • <5 small drusen • >20/30 OU 2. Category 2 • Multiple small drusen MILD ARMD • 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 INTERMEDIATE ARMD • 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 ADVANCED ARMD

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Objectives and Randomization

Study Question: Can antioxidant vitamins and minerals slow the progression of AMD and AMD-associated vision loss?

Randomized participants N=4757

Antioxidant + Placebo Antioxidant Zinc Zinc N=1483 N=1482 N=904 N=888 Mean follow–up = 6.3 yrs

AREDS Report No. 8. Arch Ophthalmol. 2001;119:1417-1436

Supplements Studied in AREDS  Antioxidants • Vitamin C – 452 mg (~5x RDA) • Vitamin E – 400 IU (~13x RDA) • Beta carotene – 15 mg*  Zinc – 80 mg , 69.6 mg label claim(~5x RDA)  Copper – 1.6 mg Produced and supplied by Bausch & Lomb via a cooperative research and development agreement

Note: Macular carotenoids lutein and zeaxanthin were unavailable commercially when AREDS was initiated *No RDA specified;

AREDS Report No. 8. Arch Ophthalmol. 2001;119:1417-1436

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

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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 report # 35 Ophthalmology E-pub 2013

AREDS 1 Conclusions

Consider Antioxidants + Zinc supplement if: • Extensive intermediate drusen • 1 or more large drusen • Noncentral geographic atrophy • Advanced AMD • Vision loss due to AMD in 1 eye AND • Non-smoker

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http://caseyamdcalc.ohsu.edu/

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

*Doubling of the visual angle or the loss of 15 or more letters on the ETDRS chart

AREDS2 protocol; version 5.2, 23 September 2009, accessed at : https://web.emmes.com/study/areds2/resources/areds2_protocol.pdf Feb 2011

Randomized Participants 4203

Control L/Z* DHA/EPA L/Z* + DHA/EPA 1012 1044 1068 1079

No ATS** ATS** PV AREDS (SOC) 19 formulations 1148 3036 *Lutein/Zeaxanthin **AREDS type supplements † AREDS formula Hi Zn + ß-C† No ß-C Low Zn No ß-C & Low Zn SOC: Standard of care 659 863 689 825 AREDS2 Report 1 Ophthalmology.2012;119:2282-9 66

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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 Research Group JAMA Epub 2013

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

* Quit smoking > 1 year before randomization

AREDS2 Research Group JAMA Epub 2013

49% Derive More Benefit from Treatment other than AREDS

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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

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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

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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

26 4/7/2017

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.

Action Steps

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