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Risk Factors determined by the Mayo Clinic

• Age. Your risk of macular degeneraon increases as you age, especially aer age 50. Macular ARMD degeneraon is most common in people older than 65. • Family history of macular degeneraon. If someone in your family had macular degeneraon, you're more likely to develop macular degeneraon. From Spinach to Injecon • Race. Macular degeneraon is more common in whites (Caucasians) than it is in other races. • Smoking. Smoking cigarees increases your risk of macular degeneraon. • Obesity. Being severely overweight increases the chance that early or intermediate macular degeneraon will progress to the more severe form of the disease. • Diet. A diet that includes few fruits and vegetables may increase the risk of macular degeneraon. • High blood pressure. Diseases that affect the circulatory system, such as high blood pressure or high cholesterol, may increase the risk of macular degeneraon. Steven M. Newman, O.D., C.N.S. • Inflammaon. Your immune system can cause swelling of your body ssues, which may Board Cerfied Optometric Physician increase the risk of macular degeneraon. Florida Board of Optometry • Cardiovascular disease. If you have had diseases that affected your heart and blood vessels (cardiovascular disease), you may be at higher risk of macular degeneraon Board Cerfied Nutrion Specialist American College of Nutrion

ARMD genecs Hippocrates

– Alternate complement pathway – ARMS2/HTRA1 – HDL cholesterol pathway “He who does not know – Extracellular matrix – Angiogenesis pathway food, how can he – Vitamin D pathway understand the diseases of man?”

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Our body was designed to absorb nutrients the old fashioned way…by eang natural foods rich in anoxidants. Locally grown, organic fruits and vegetables contain the essenal vitamins and nutrients necessary for opmal health.

AREDS 2 AREDS 2 is a mul-center randomized trial designed to assess the effects of oral supplementaon of high doses of macular xanthophylls ( and ) and/or omega -3 LCPUFAs (DHA and EPA) for the treatment of AMD and . All parcipants will be offered addional treatment with the study formulaon used in AREDS. For those who elect to take this addional supplement, which is now considered the standard of care, further randomizaon may occur to evaluate the possibility of deleng beta-carotene and decreasing the original levels of zinc in the formulaon for the treatment of AMD, if consent is obtained.

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Study Chair: Emily Chew, MD AREDS 2 The primary objecve of AREDS 2 is to evaluate the effect of dietary Naonal Eye Instute (NEI) xanthophylls (lutein/zeaxanthin) and/or omega -3 LCPUFAs (DHA and EPA) on progression to advanced AMD. This objecve will be Division of Epidemiology and Clinical Research accomplished by collecng and assessing the data on Clinical Trials Branch approximately 4,000 AREDS 2 parcipants aged 50 to 85 years, Bldg. 10, CRC, 3-2531 who at the me of enrollment have either:

10 Center Drive, MSC 1204 Bethesda, MD 20892-1204 1. bilateral large drusen or Tel: 301-496-6583 Fax: 301-496-7295 2. large drusen in one eye and advanced AMD (neovascular AMD or central geographic atrophy) in the fellow eye. E-mail: [email protected]

The objecves of AREDS 2 are to: Study the effects of high supplemental doses of the dietary xanthophylls (lutein and zeaxanthin) and omega -3 LCPUFAs (DHA If the parcipant is a current smoker or a former and EPA) on the development of advanced AMD. smoker that has quit within the last year, he Study the effects of these supplements on cataract and moderate vision loss (doubling of the visual angle or the loss of 15 or more or she will be randomized to one of the two leers on the ETDRS chart). arms without beta-carotene (Formulaons 2 Study the effects of eliminang beta-carotene in the original AREDS formulaon on the development and progression of AMD. or 3). If a parcipant does not consent to Study the effects of reducing zinc in the original AREDS formulaon on randomizaon but wants to take the AREDS the development and progression of AMD. formulaon, he or she will be provided the Validate the fundus photographic AMD scale developed from the Age- Related Study. supplements provided that they are not a Enrollment concluded in June 2008 and parcipants will be followed between five and six years. current smoker or a former smoker that has quit within the last year.

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Known for years

Too much Zinc is bad for us. It actually causes us to age more rapidly.

Most vitamin manufacturers, especially the ones owned and operated by optometrists, reduced their zinc concentraons years ago.

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Recent Conclusion

Perceived: AREDS 2 recently concluded that supplemenng with Omega 3’s did not show any benefit towards halng or reversing macular degeneraon.

Actual: The amount of ethyl-ester (Triglyceride form is the natural form) Omega 3 used in the AREDS 2 study did not show any benefits towards halng or reversing macular degeneraon.

AREDS take home message Top Ten Vitamin C Foods

1. Green Chilis – 245mg/100g 2. Guava – 228mg/100g Anoxidants 3. Bell Peppers – 184mg/100g (341/pepper) 4. Fresh Herbs – Thyme / Parsley – 160mg/100g Especially Vitamin C 5. Green Leafy Vegetables – 120mg/100g Are beneficial for people 6. Broccoli (Cauliflower / Brussels Sprouts) – 89mg/100g Suffering from ARMD 7. Kiwi – 93 mg/100g 8. Papaya – 62mg/100g 9. Orange – 59mg/100g 10. Strawberry – 59mg/100g

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RAW FOODS

Food source in most natural state Diet rich in fruits and vegetables Healthy via nuts PH levels naturally increase Easier to follow due to access

Really???

All parcipants in AREDS 2 taking a daily mulvitamin and/or mulmineral supplement will be asked to replace it with Centrum Silver®. This product will be provided free-of- charge (you get what you pay for).

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Hippocrates

“If we could give every individual the right amount of nourishment and exercise, not too lile and not too much, we would have found the safest way to health.”

Phototrop Study

Improvement of Visual Functions and Fundus Alterations in Early Age-Related Treated with a Combination of Acetyl- L -Carnitine, n-3 Fatty Acids, and Coenzyme Q10

Ophthalmologica 2005;219:154–166J

Fehera B. Kovacs I. Kovacs M. Schvöller A. Papale C. Balacco Gabrieli Ophthalmic Neuroscience Program, Department of , University of Rome ‘La Sapienza’, Rome ,Italy Department of Ophthalmology, University of Pecs, Pecs , and Second Department of Ophthalmology,Semmelweis University, Budapest , Hungary

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Study Medicaon consisted of 2 oral The aim of this randomized, double-blind, placebo- capsules per day, containing either: controlled clinical trial was to determine the efficacy of a combination of 100 mg of ALC Acetyl- L –Carnitine 530 mg of n-3FA 10 mg of CoQ10 n-3 Fatty Acids and Coenzyme Q10 (Phototrop ® ) or on the visual functions and an equal quanty of soy oil. fundus alterations in early age-related macular degeneration

Inclusion criteria

Have a diagnosis of early bilateral AMD Have a visual acuity between 8/10 and 4/10 (Snellen chart decimal scale) Be 55–70 years old and of Caucasian origin Agree to disconnue any current vitamin regimen Be highly movated, alert, oriented, mentally competent and able to understand and comply with the requirements of the study, abide by the restricons and return for all required visits Provide wrien informed consent

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Exclusion Criteria Exclusion Criteria

Late AMD (geographic atrophy or macular scarring) Severe or uncontrolled hepac, renal, pulmonary, and thyroid disease or Exudave renal disease, including exudave AMD History of HIV infecon, hepas B or C, or other Clinically significant corneal opacity or immunosuppressive disorders Inherited renal dystrophies or degenerave myopia History of alcoholism, drug abuse, severe mental disorders Unstable glaucoma Were a praccing vegetarian or had an abnormal diet (<1,600 or >3,500 kcal/day) PVR, rhegmatogenous renal detachment Poor general health or unstable diseases Opc nerve disease Known or suggested hypersensivity to study compounds Acve intraocular inflammatory disease Use of corcosteroid, phenothiazine and anmalarial drugs Refracve error over +4 D and –6 D within 1 month prior to visit 1 or during the 12-month study Significant cardiovascular or cerebrovascular diseases period

Acetyl L Carnine Foods Containing Acetyl L-Carnine

Acetyl L Carnine is a supplement to help Organic Grass Fed Beef – 81mg/3oz. people burn unwanted or excess body . Pork – 24mg/3oz. Acetyl L-Carnine, also known simply as L- Organic Cow’s Milk – 8mg/8oz.

Carnine, transports fay acids across the Vegetables in general do not make good sources of carnine. However, there are two vegetables that contain small amounts of carnine. inner mitochondra membrane where they are burned and used as energy. Without acetyl L- Avocados have the largest carnine count in the vegetable food Carnine, fay acids pile up, leading to weight group, with 2 mg per 1 medium avocado

gain. L-Carnine also helps enhance memory; Six spears of asparagus, or ½ cup, contains .2 mg of carnine some people take it to help combat

Alzheimer's disease.

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Co-Q-10

Coenzyme Q10, commonly shortened to CoQ10, is a fat-soluble nutrient found throughout the human body. Recently, CoQ10 has become very popular as a dietary supplement and nutrional medicine. Though evidence is sll under invesgaon, CoQ10 shows promise in prevenng or treang common disorders. It is also referred to as ubiquinone

Cholesterol lowering agents Deplete our body of The "Q" in Coenzyme Q-10 refers to quinone, a chemical family that includes CoQ10 and several other biologically essenal substances, such as vitamin K1. This is also reflected by the chemical's other name, Vitamin A ubiquinone--a blend of "ubiquitous" because it is found throughout the body, and "quinone" because of its chemical makeup. Vitamin B12 CoQ10 is present in nearly every cell of the body, and is collected in cellular mitochondria. It is an essenal part of the process of cellular Vitamin D respiraon, which creates ATP, the nucleode responsible for nearly Vitamin E all of the body's energy producon. Though it is found throughout the body, CoQ10 is most highly concentrated in the organs that require Vitamin K the most energy transfer, Co-Q-10 such as the heart Beta-Carotene

Folic acid Iron

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Foods That Contain Co-Q-10 Phototrope Study Results

Organic, grass fed meats contain a high concentraon of Improvement was found in each of the CoQ10. A report from Iowa State University lists beef, four parameters chicken and pork as all containing between 1.2 and 2.6 milligrams (mg) of CoQ10 in a three ounce serving, of visual functions in the most affected eyes of with beef containing the most at 2.6 mg per serving. EARLY AMD patients Fish also contain higher levels of CoQ10. Marinated herring is listed by the Linus Pauling Instute (LPI) as taking Phototrop. It is particularly important that containing 2.3 mg per three ounce serving. Following VFMD (Visual Field Mean Deviation, the primary herring is rainbow trout at 0.9 mg and salmon at 0.4 efficacy variable), visual acuity and mg per three ounce serving. foveolar sensitivity (secondary efficacy variables) showed statistically significant differences in

changes comparing treated with placebo groups.

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Absorpon

Transport and Retinal Capture of Lutein and Zeaxanthin with Reference to ARMD Several processes are required for opmal absorpon of carotenoids. These include Survey of Ophthalmology Volume 53 No. 1 Jan-Feb 2008 adequate digeson of the food matrix in order to release the carotenoids, formaon of lipid micelles in the small intesne, uptake of the carotenoid by intesnal mucosal cells, and transport of carotenoids to the lymphac or portal circulaon.

Transport Capture

The majority of plasma carotenoids are transported on LDL, with 55% of total Renal capture of the xanthophyll carotenoids is carotenoids associated with it, whereas HDL is mediated largely by a specific xanthophyll associated with 33% and VLDL 10-19% binding protein (XBP), specifically the Pi respecvely isoform of GSTP1 in the case of zeaxanthin. The specific binding protein for lutein remains

elusive. Lutein and Zeaxanthin are equally distributed between LDL + HDL molecules

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Conclusion

The authors concluded that in order to fully explore the potenal beneficial effects of lutein and zeaxanthin, in parcular in the context of their punive role in the prevenon of AMD, it is essenal that we understand the mechanisms by which they are absorbed from the GI system, transported in the serum and taken up by the rena.

LAST study

Double-masked, placebo-controlled, randomized trial of lutein and anoxidant supplementaon in the intervenon of atrophic ARMD: the Veterans LAST study

(Lutein Anoxidant Supplementaon Trial) Optometry Vol. 75 No. 4

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Conclusion Foods That Contain Lutein

Vegetable/Fruit Lutein or Zeaxanthin (Micrograms) (100 grams or 1/2 cup)

Kale 21900 The LAST study concluded that visual funcon is Collard Greens 16,300 improved with lutein alone or lutein together Spinach, cooked & drained 12,600 with other nutrients. Cress Leaf raw 12,500 Swiss Chard raw 11,000 Chicory Leaf raw 10,300 Parsley 10,200 Spinach raw 10,200

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Foods That Contain Lutein LAST 2 study

Vegetable/Fruit Lutein or Zeaxanthin (Micrograms) (100 grams or 1/2 cup)

Mustard Greens 9,900 Differenal temporal responses of macular Beet Greens 7,700 pigment opcal density in paents with Okra 6,800 Red Pepper 6,800 atrophic ARMD to dietary supplementaon Dill 6,700 Romaine Leuce 5,700 with xanthophylls Endive 4,000 Celery 3,600 Scallions 2,100 Optometry (2007) 78, 213-219 Leeks 1,900 Stuart Richer, O.D., Ph.D. Jenny Devenport, Ph.D. John C. Lang. Ph.D. Broccoli, cooked 1,800

LAST 2 study Objecve LAST 2 Results The LAST study was to determine whether specific dietary intervenons increased macular pigment opcal density (MOPD) and visual funcon in paents with atrophic MPOD increased with supplementaon and ARMD. decreased without. The highest increases in MOPD over me occurred in paents with lower baseline values of MPOD. The LAST 2 objecve is to discern those specific characteriscs that increase MPOD.

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LAST 2 Conclusion

Noteworthy is the observaon that those individuals with the lowest MPOD, and in greatest need of supplementaon, were also most likely to benefit from either lutein or lutein plus anoxidant supplementaon.

Lycopene but not Lutein nor Zeaxanthin decreases in serum lipoproteins in ARMD paents

Clinica Chimica Acta 357 (2005) 34-42

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Study Objecves Results

No difference was observed between ARMD Epidemiological studies have established that a paents and the control subjects in total serum carotenoids. low serum concentraon of carotenoids was

associated with ARMD. The aim of this study Concentraons in serum and lipoparcle fracons was to determine carotenoid levels in serum of lutein + Zeaxanthin were also equal between and in different lipoprotein fracons in the two groups. paents diagnosed with ARMD and in a matched control group. Serum and lipoparcle fracons of Lycopene was significantly decreased in ARMD paents.

Conclusion

Lycopene, a liposoluble anoxidant nutrient, is the only carotenoid altered in ARMD paents.

There he goes talking about fresh fruits again

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Plato Risk Reducon Recommendaons Reduce Weight Stress Smoking Rx medicaons

Increase “We shall eat animals Exercise Awareness of Diet Level of Happiness only at our own peril.” Supplement Use

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There’s nothing wrong with talking to your paents about exercise as a way to reduce their risk of AMD by reducing their body weight.

Risk factor dealt with: Obesity

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Aflibercept - Eylea

Intravitreal Aflibercept for Treatment-Resistant Neovascular Age-Related Macular Degeraon

Ophthalmology Vol 121 No.1 January 2014

Objecve Intervenon

To assess the effecveness of intravitreal aflibercept in paents with neovascular age- A dose of 2mg intravitreal aflibercept was related macular degeneraon previously administered as 3 inial loading doses every 4 resistant to treatment with other an-vascular weeks, followed by further injecons every 8 endothelial frowth factor agents. weeks across a 24-week period in total.

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Main Outcome Measures Results

BCVA improved and CRT was reduced Outcomes assessed included proporons of significantly at all follow-up visits compared with paents with a gain or loss of more than 5 baseline (P<0.0001), with a mean improvement ETDRS leers and a decrease or increase in of 6.9 leers of BCVA and a decrease of 89.4um central renal thickness of more than 150 um at in CRT at week24. Spacing of injecons from week 24 compared with baseline, change in every 4 weeks to every 8 weeks resulted in an mean BCVA and CRT between baseline and increase of 37.4um in CRT (P<0.0001); however, week 24, and descripve safety data. this was not correlated with a significant change in vision.

Conclusion

Intravitreal Aflibercept is effecve in previously treatment-resistant Age-Related Macular Degeneraon

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