A New Look At

6/7/21

Disclosures

Leo Semes, OD, FAAO, FACMO A NEW LOOK AT AMD Speaker Bureau, Consultant - Maculogix UTAH OPTOMETRIC ASSOCIATION ANNUAL CONGRESS Speaker Bureau - Regeneron 2021 Scientific Advisory Board - EyePromise Stock options - Eye Promise (< 0.01% ownership), HPO (< Leo Semes, OD, FAAO 0.01% ownership) Professor Emeritus of Optometry and Vision Science UAB

Discovery favors the prepared mind. -Pasteur

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Disclaimer

“Half of what you'll learn during training will be shown to be either dead wrong or out-of-date within 5 years ; How important is …the trouble is that nobody can tell you which half.” vision?

-David Sackett, MD Widely regarded as the father of evidence-based medicine. (1938-2015)

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RESULTS: Vision is this important Decadal increase in AMD cases (18%) 2000-2010

• The average person with 20/40* vision in the better-seeing eye was wiling to trade 2 of every 10 [remaining] years of life in return for perfect vision,

• while the average person with severely impaired vision in the better eye was willing to trade approximately 5 of every 10 remaining years of life in return for perfect vision.

G C Brown. Vision and quality-of-life.Trans Am Ophthalmol Soc. 1999; 97: 473–511.

https://nei.nih.gov/eyedata/amd

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February was established AMD awareness month in 2008 by Prevent Blindness

https://nei.nih.gov/eyedata/amd

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How many states have only four letters? Early Symptoms: • None to vague visual impairment in reduced light* Later Symptoms: • Clue: Ohio is not one, but UTAH is. • Reduced central vision / details lost in straight ahead gaze

Clinical Diagnosis: • Dilated eye exam, dark-adaptation testing, sophisticated imaging What is AMD?

Management options: • Lifestyle modifications, dietary supplements (vitamins & minerals); and in later stages injections, laser treatment

https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and- diseases/age-related-macular-degeneration Accessed September 24, 2020

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Leading Cause of Legal Blindness in the US Polling question

According to research from UAB, ophthalmic practitioners Prevalence of Major Eye Diseases (US): Age 50 and Older fail to diagnose early AMD changes in what percentage of 12 11.2

Clinical AMD 10 patients?

is more prevalent 8 6.7 A. 10 than glaucoma & 6 B. 15 diabetic retinopathy 4

Millions of People 2.4 C. combined 2 20 0 D. 25 (Statistics from the AAOphth) Open Angle Di a beti c Reti nopa th y AM D Gl a uc oma

Sources: https://www.aao.org/newsroom/eye-health-statistics#_edn4; https://www.nei.nih.gov/learn-about-eye- health/resources-for-health-educators/eye-health-data-and-statistics/diabetic-retinopathy-data-and- statistics/diabetic-retinopathy-tables; https://www.nei.nih.gov/learn-about-eye-health/resources-for-health- educators/eye-health-data-and-statistics/glaucoma-data-and-statistics/glaucoma-tables

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Recent report

20/60 20/40 “I woke up in the middle of the night and I couldn’t see the middle number on the digital clock with my right eye.

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73 yo White Male • Followed for 2+ years for dry AMD (pre-AREDS) • Taking 6 mg Lutein/day + Centrum Silver • And a host of medications • BCVA 20/40+, 20/40+ (at baseline) 20/60 • Drusen and pigment changes in each macula

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Underdiagnosis of early AMD

January 1. 2020

ü Mean age 81 years ü Baseline VA 20/80

ü At one year following a mean 7.4 injections, mean VA gain: 0.77 - 1.13 letters

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Underdiagnosis of early AMD

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AMD STAGING REVIEW (AND UPDATE)

Specifications derived from the AREDS, CARMS and the European System

*Categories not mutually exclusive, so %-ages do not add to 100

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Polling question

Identification of a single large druse (> 125 u), would be consistent with which of the following Categories of AMD as derived from the AREDS? A. 1 HOW IS AMD B. 2 STAGED? C. 3 Guidance from the AREDS D. 4 (The Age-related eye disease study)

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Simplified AREDS Staging (specification) Simplified AREDS Staging (specification) Category 1 Category 3/Intermediate • No or few drusen (<63 microns*), − Combo of extensive no pigment abnormalities, intermediate neither eye Wet or any large druse, or GA • 0% risk of Wet at 5 yrs − 18% risk of Wet in 5 yrs Category 4/Advanced/ Category 2 High Risk • Intermediate drusen − One eye with Wet or (<125 microns*), mild pigment BCVA worse than 20/32 abnormalities, neither eye wet from Dry Note that to be enrolled in AREDS, patients had to have • <2% risk of Wet at 5 yrs at least moderate AMD and be > 50.

http://www.nei.nih.gov/amd/background.asp BCVA=best corrected visual *Note: Central retinal vein is approximately 125 microns http://www.nei.nih.gov/amd/background.asp acuity LS GA=geographic atrophy

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Dry AMD Wet AMD

• The clinical • The clinical presentation of “Dry,” presentation of “Dry,” plus development of plus development of either: either: • subretinal choroidal • subretinal choroidal neovascular neovascular membranes (CNVM) membranes (CNVM) • subretinal hemorrhage • subretinal hemorrhage • RPE detachment • RPE detachment

Photos Courtesy of Mark T. Dunbar, OD

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Natural Course of AMD Make a careful distinction Without treatment, chance of severe vision loss and legal blindness is high1 Significant chance of 2nd eye becoming affected • Specification vs. •Performance • Annual rate of 4%-12% • Unilateral neovascular AMD becomes bilateral in >40% at 5 yrs2 As population ages, more people will have wet AMD; approximately 7.5 million in developed countries • 461 HP by 2020

• 17” brakes

• 35 ft3 cargo space

1. Bressler SB et al. Am J Ophthalmol. 1982;93(2):157- 163.2. Macular Photocoagulation Study Group. Arch Ophthalmol. 1993;111(9):1189-1199.

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Emily Chew quote regarding prophylaxis

“ It would be great to have the opportunity to study primary prevention of AMD. STAGING RISK FOR VISION I think the pathways to drusen and then from drusen to LOSS SECONDARY TO AMD advanced disease might be quite different. A multi-factorial disease Those pathways need to be elucidated….” Simplified AREDS, STARS (European). First steps to having an impact on vision loss from AMD

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Ferris FL, et al. Ophthalmology. 2013 Apr;120(4):844-51

Ferris FL, et al. Ophthalmology. 2013 Apr;120(4):844-51 Ferris FL, et al. Ophthalmology. 2013 Apr;120(4):844-51

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Simplified risk scoring system (Rapid AMD is a Major Health Problem & Economic Burden assessment of risk from STARS) Focus on this number • Age (>85) AMD presents serious consequences for the US population as a whole Total loss in • Family history of AMD Prevalence of Common Chronic Diseases (US) gross domestic 25 product in the 20.9 US $41B due to AMD is • Hyperopia 20 estimated at more than 15 DIRECT DIRECT INDIRECT DISEASE STAGE MEDICAL NON-MEDICAL • Cataract surgery 11.2 COSTS COSTS COSTS 10 Outpatient None None Drusen monitoring Millions of People 5.7 • North African ethnicity (vs. Caucasian) 5 Outpatient Living aids Caregiving Dry monitoring, (limited), Home (limited), Lost Vitamins/ modifications productivity supplements (limited) (limited) 0 Outpatient Living aids, Caregiving, • History of atherosclerosis Wet monitoring, Home Lost Alz heimer's D isease AM D All Canc er s Treatment modifications productivity

• History of smoking (former,

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Why are mammograms performed? EARLIEST IDENTIFICATION OF AMD What you can’t see may be harmful!

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Cuticular drusen – not just in the posterior pole anymore Cuticular drusen – not just in the posterior pole anymore Ultrawide color and FA Ultrawide color and Fundus imaging of a 51 YO with Autofluorescence peripheral cuticular drusen. imaging of a 51 YO with peripheral cuticular drusen. Note RPE abnormalities (hyper and hypo) Note RPE abnormalities (hyper and hypo)

Balaratnasingam C, et al. Cuticular Drusen: Clinical Phenotypes and Natural History Defined Using Peripheral and posterior pole Multimodal Imaging. Ophthalmology. 2018 patterns are similar Jan;125(1):100-118.

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A B C D Here’s what’s interesting about this cohort 4 imaging modalities (240 eyes, 120 patients) (from Denmark)

A. Fundus photography B. SD-OCT C. AOSLO Adaptive optics scanning laser ophthalmoscopy, confocal D. AOSLO + split detection methods Conclusions. Small hard drusen could arise from single RPE lesions or a small cluster of 2-3 RPE cells. Pedersen HR, et al. Multimodal imaging Balaratnasingam C, et al. Cuticular Drusen: Clinical Phenotypes and of small hard retinal drusen in young Natural History Defined Using Multimodal Imaging. Ophthalmology. 2018 healthy adults. Br J Ophthalmol. 2018 Jan;125(1):100-118. Jan;102(1):146-152. 41 42

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Multi-modal imaging of drusen in young Polling question patients (Denmark) The recently established gold standard biomarker for early AMD is which of the following?

A. Prolonged or impaired dark adaptation B. Fundus autofluorescence (FAF) C. Observation of small drusen (< 63 u); so-called druplets D. Scanning-laser ophthalmoscopy/Adaptive optics imaging of RPE irregularities

Pedersen HR, et al. Multimodal imaging of small hard retinal drusen in young healthy adults. Br J Ophthalmol. 2018 Jan;102(1):146-152.

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What do you notice about this pristine looking retina?

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AMD Pathogenesis • Cholesterol deposition Photoreceptors BlinD and BlamD • These deposits eventually become clinically visible drusen Druse • These extracellular cholesterol deposits affect RPE photoreceptor health, Bruch’s Membrane causing inflammation This is Druse, it’s an alligator! and predisposing to CNV • In addition, they impair nutritional transport, including that of Sclera Curcio CA, Johnson M. Structure, function, and pathology of Bruch’s membrane. vitamin A, across In: Ryan SJ, et al, eds. Retina, Vol 1, Part 2: Basic Science and Translation to Therapy. 5th ed. London: Elsevier; 2013:466–481. Bruch’s membrane

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AMD Pathogenesis

Photoreceptors In effect, early precursors to AMD cause a localized Druse deficiency of

RPE vitamin A, and dark Bruch’s Membrane adaptation [DA] is the best measure of this change

Meet Druse close up Sclera Curcio CA, Johnson M. Structure, function, and pathology of Bruch’s membrane. In: Ryan SJ, et al, eds. Retina, Vol 1, Part 2: Basic Science and Translation to Therapy. 5th ed. London: Elsevier; 2013:466– 481.

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Histology of basal linear and laminar deposits (still specification)

IMPAIRED DA IS DIRECTLY RELATED TO SUBCLINICAL

calcified druse ANATOMICAL CHANGES SDD = subretinal dresenoid deposits d = druse Let’s look at visual performance

Pilgrim MG, et al. Subretinal Pigment Epithelial Deposition of Drusen Components Including Hydroxyapatite in a Primary Cell Culture Model. Invest Ophthalmol Vis Sci. 2017 Feb 1;58(2):708-719.

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1202 eyes (958 normal, 244 with early AMD), Make a careful distinction as graded by AREDS classification. • Specification vs. •Performance • Data collection • Visual function testing (Specification) (Performance) • Color Fundus • BSCVA (photopic) • 461 HP • 0-60 MPH in 4.2 sec. Photography [CFP], • Contrast and light • IR reflectance imaging, sensitivity • Fundus • Mesopic visual acuity • 17” brakes • 100MPH to speed limit autofluorescence [FAF] • Low-luminance deficit and and 3 • SD- OCT (Spectralis) • Rod-mediated dark • 35 ft cargo space • Will 4 sets of golf clubs adaptation fit behind the second row of seats? Neely D, et al. ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES. Retina. 2017 Jul;37(7):1329-1336. 53 54

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Subretinal drusenoid deposits (SDD) Results (prolonged rod-intercept time (RIT) (demonstration methodology) • Visual function/performance testing failed to distinguish • SD-OCT – primary triage between eyes with vs. those without SDDs, with the • Followed by the grading of the 3 en-face imaging modalities. [CFP, IR, FAF,] exception of Dark Adaptation.

• Criteria for SDD at the eye level(clinically) required identification on > 1 en face modality and OCT or

• on >2 en face modalities in the absence of OCT findings (called strict criteria)

Neely D, et al. ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID Neely D, et al. ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES. Retina. DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES. Retina. 2017 Jul;37(7):1329-1336. 2017 Jul;37(7):1329-1336. 55 56

Example Example

NOTE: RIT times

IR reflectance image and corresponding SD-OCT X-section IR reflectance image and corresponding SD-OCT X-sections Left: Normal macula Right: Normal macula with subtle SDD Left: Early AMD Right: Early AMD with subtle SDD Neely D, et al. ASSOCIATION BETWEEN VISUAL FUNCTION Neely D, et al. ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID ANDNOTE SUBRETINAL RIT timesDRUSENOID DEPOSITS IN NORMAL AND DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES. Retina. EARLY AGE-RELATED MACULAR DEGENERATION EYES. 2017 Jul;37(7):1329-1336. Retina. 2017 Jul;37(7):1329-1336. 57 58

DA results for 4 representative cases Conclusion Eyes with clinically normal ocular health and early AMD who have been identified with SDDs warrant careful scrutiny because of their increased risk for incident early AMD and its progression. (LS) Note RIT times

Neely D, et al. ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID Neely D, et al. ASSOCIATION BETWEEN VISUAL FUNCTION DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES. Retina. AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND 2017 Jul;37(7):1329-1336. EARLY AGE-RELATED MACULAR DEGENERATION EYES. Retina. 2017 Jul;37(7):1329-1336. 59 60

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Prolonged Dark Adaptation Is NOT a Risk Factor for AMD AAO Preferred Practice Pattern® for AMD Impaired dark adaptation is NOT a risk factor.

It IS the earliest manifestation of disease.

Genetic testing and macular pigment density (MPOD) can indicate a heightened risk for developing AMD, but neither indicates the actual presence of disease.

Performance ! American Academy of Ophthalmology. “Preferred Practice Pattern for AMD.” (2015)

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ALSTAR Study Results ALSTAR Study • Impaired dark adaptation identifies subclinical AMD (SDD) at least three years before it can be seen with standard clinical methods. • Subjects with impaired dark adaptation were 2X likely to develop clinically evident AMD and 8X likely to advance beyond the earliest stage of AMD. Prospective Study of Subclinical AMD Sample consisted of 325 adults without clinically detectable AMD. At baseline, 24% of the subjects exhibited impaired dark adaptation. AMD status determined at 3-year follow-up visit.

RI > 20 minutes

Owsley, C et al. Ophthalmology. 2016;123(2):344-351. Owsley, C et al. Ophthalmology. 2016;123(2):344-351.

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Case Example 3: 67 WM Dark Adaptation screening protocol

RIT = rod-intercept time

Normal rod-intercept “R/C break” RIT = 4.1 min. (OS) Jackson GR, et al. Vision Res. 1999;39(23):3975-3982. Leibrock CS, et al. Eye (Lond). 1998;12(pt 3b):511-520.

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Aren’t the anti-VEGF agents the saving grace for nAMD?

EARLY DIAGNOSIS – SO WHAT?

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Published March 21, 2021 Aren’t the anti-VEGF agents the saving grace for nAMD? Aren’t the anti-VEGF agents the saving grace for nAMD?

Mmmmmm, No. But that was 2020…

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Polling question

Aren’t the Which of the following risk factors do you use to profile risk anti-VEGF for developing AMD (Select all that apply) agents the • A. Smoking status saving • B. Visual impairment in dark or dim illumination grace for • C. Fundus observation/Color fundus photography nAMD? • D. Dietary/Lifestyle characteristics • E. Family history of AMD • F. Genetic testing

Well, no. 77 78

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AMD Risk Factors Non-Modifiable Modifiable Age (chronological) Smoking Gender Cardiovascular Hereditary: Genetics disease Race/Pigmentation Dietary intake http://www.brooklineconnection.com/hi Alcohol intake story/Facts/images/Point2014.JPG Light exposure Nutrition / MPOD

MPOD=macular pigment optical density

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Lifestyle Profile Practical dry AMD management Once detected, early interventions can slow disease progression

• Do you smoke? Five proven approaches to modifiable risk factors • How is your diet? • How often do you eat fish? • How often do you drink wine? • Describe your lifestyle, activity, exercise, meals

Diet & Exercise Nutritional Supplementation Systemic Disease Retinal Light • How well do you think Smoking Cessation Management Protection you see? • What is your family history of AMD? Leading optometrists agree: Practical treatments should be used for ALL STAGES OF AMD to slow progression and improve outcomes.

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Dietary and Lifestyle Modifications 1 2 Smoking Cessation Mediterranean Diet, for example Smoking is the largest • Having a combination of 3 healthy behaviors modifiable risk factor (healthy diet, physical activity, and not smoking*) for AMD was associated with 71% lower odds for AMD Current smokers carry a 2.5 to 4.8 times • High fat diet was strongly associated with a higher risk than non-smokers for late AMD higher prevalence of advanced AMD (OR: 3.70) However… • Low fat diet including whole grains, fruit, of patients of smokers with AMD < know tomatoes, green leafy vegetables, low-fat dairy, 90 were not 50% maysmoking contribute fish, and seafood, was protective from advanced advised to stop to blindness smoking AMD (OR: 0.38) % MARES, J. A. (2011). ARCHIVES OF OPHTHALMOLOGY, 129(4), 470. | RINNINELLA, E., ET AL.. NUTRIENTS, 10(11), 1677. **TRADEMARKS ARE THE PROPERTY OF THEIR RESPECTIVE OWNERS.**

SOURCES: 1 CHAKRAVARTHY U.ET AL. CIGARETTE SMOKING AND AGE-RELATED MACULAR DEGENERATION IN THE EUREYE STUDY. OPHTHALMOLOGY. 2007;114(6):1157-1163. | 2 CABAN-MARTINEZ AJ ET AL. AGE-RELATED MACULAR DEGENERATION AND SMOKING 83 FOURCESSATION-YEAR ADVICEINCIDENCE BY EYEAND CARE PROGRESSION PROVIDERS. OF PREVAGE- RELATEDCHRONIC MACULARDIS. 2011;8 DEGEN(6):A147ERATION: | 3 HANDA THE S ET LOS AL. ANGELES AWARENESS LATINO OF EYEBLINDNESS STUDY. ANDAM J OTHER OPHTHALMOL. SMOKING 2011-RELATED;152(3):385 DISEASES-395. **TRADEMARKS … IN EYE PATIENTS. ARE THE EYE. PROPERTY 2011;25(9):1170 OF THEIR-1176. RESPECTI | CHOUDHURYVE OWNERS.** F, ET AL. RISK FACTORS FOR 84

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USDA Dietary Guidelines for Americans A useful resource for practitioners and interested patients

“Let food be thy medicine and medicine be thy food.”

AVAILABLE AT: HTTPS://HEALTH.GOV/OUR-WORK/FOOD- NUTRITION/2015-2020-DIETARY-GUIDELINES/GUIDELINES/ ACCESSED OCTOBER 1, 2020

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USDA MyPlate USDA MyPlate

The take-home here is that dairy should be an The take-home option and that here is that dairy fruits and vegetables should be an option should comprise 50% and that fruits and of dietary intake vegetables should comprise 50% of dietary intake

HTTPS://HEALTH.GOV/OUR-WORK/FOOD-NUTRITION/2015-2020-DIETARY-GUIDELINES/GUIDELINES/ ACCESSED OCTOBER HTTPS://HEALTH.GOV/OUR-WORK/FOOD-NUTRITION/2015-2020-DIETARY-GUIDELINES/GUIDELINES/ ACCESSED OCTOBER 87 1, 2020 88 1, 2020

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Lifestyle Modifications 2a Exercise

• Physical activity was found to have a protective association with both early AMD and late AMD

Pooling data from RS-I and Alienor, higher adherence to the MeDi • Engaging in an active lifestyle reduced risk of developing nAMD over 15 years by was associated with a 41% reduced risk of incident advanced * AMD. 70%

These findings support the role of a diet rich in healthful nutrient- • Walking more reduced the risk of rich foods such as fruits, vegetables, legumes and fish in the developing nAMD over 15 years by 30% prevention of AMD.

LIU, L., MAJITHIA, S., & THAM, Y.-C. (2018). AMERICAN JOURNAL OF OPHTHALMOLOGY, 185, 123. | KNUDTSON, M. D., ET AL. PHYSICAL ACTIVITY AND THE 15-YEAR CUMULATIVE INCIDENCE OF AGE-RELATED MACULAR 90 DEGENERATION: THE BEAVER DAM EYE STUDY. BRITISH JOURNAL OF OPHTHALMOLOGY, 90(12), 1461–1463. **TRADEMARKS ARE THE PROPERTY OF THEIR RESPECTIVE OWNERS.**

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Polling question https://health.gov/our-work/food-nutrition/2015-2020-dietary-guidelines/guidelines/ Accessed October 1, 2020 Make healthy behavioral shifts Which of the following categories of supplements do you recommend for your patient when you make a diagnosis of AMD? (Select all that apply) Try to get 150 minutes of physical activity weekly A. Carotenoids (e.g., Lutein, zeaxanthin, astazanthin, meso-zeaxanthin) That’s 30 minutes 5 B. Antioxidants times/week C. Omega-3s (PUFFAs)/fish oil D. CoQ-10 “Sitting is the new smoking.”* E. Gingko Biloba *https://theheartfoundation.org/2019/08/10/is-sitting-the-new-smoking/ F. The AREDS formulation HTTPS://HEALTH.GOV/OUR-WORK/FOOD-NUTRITION/2015-2020-DIETARY-GUIDELINES/GUIDELINES/ ACCESSED OCTOBER 1, 2020

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Nutritional Supplementation 3 Chew, E. Y., et al. Ophthalmology, 120(8). **Trademarks are the property of their respective owners.**

• The first AREDS trial showed that antioxidant vitamins and mineral supplements reduce the risk of developing advanced AMD by about 25% • Subjects who were at high risk for developing the Global Supplement advanced stage of this disease also reduced vision loss by 19% RECOMMENDATIONS AREDS 2, Rotterdam, Tufts NE medical center

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• Patients aged 50-85 years who are at high risk for progression of AMD, especially those who do not eat well, should use a supplement that contains 10 mg “…dietary -3 long-chain #1 Take-Home lutein, 2 mg zeaxanthin, and no beta- report #23 Message carotene polyunsaturated fatty acid intake is (AREDS 2) associated with a decreased risk of • L/Z was associated with additional reduction in risk progression from bilateral drusen to for progression, beyond the original AREDS CGA.” supplement: • By 26% in patients with low dietary intake of L/Z • By 18% L/Z vs beta-carotene

• Beta-carotene did not affect the risk for progression and SanGiovanni JP , et al. The Relationship of Dietary -3 Long-Chain Polyunsaturated Fatty Acid Intake Agesignificantly-Related Eye Disease increased Study 2 the Research risk for Group. lung JAMA. cancer 2013;309(19):2005-2015. With Incident Age-Related Macular Degeneration Arch Ophthalmol. 2008;126(9):1274-1279.

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Recommended Supplements for Age-related Macular Degeneration – Tufts NE Medical Center Results (4170 followed; 560 incident AMD @ 8-yr F/U) • Lutein, 6-10 mg Dietary • High dietary intake of vitamin E (whole grains, antioxidants vegetable oils, eggs, nuts) and Zinc (meat, poultry, fish • Vitamin C, 500 mg and AMD risk – whole grains, dairy) was protective • Vitamin E, 200 – 400 IU corroborating • Vitamin D3, 1000 – 2000 IU evidence • Above-median intake of C, E, beta-carotene (carrots, (Rotterdam kale, spinach), and Zn lowered risk ~ 35% • Zeaxanthin, 2 mg Study) • May also include Zinc, 20 – 80 mg • Conclusion (Rotterdam Study) • “Dietary anti-oxidants may delay the development of early AMD and, possibly, of AMD in general.” Omega-3 fatty acids, 1000 mg (fish oil) if not eating fish

Van Leeuwen R, et al. JAMA 2005; 294(24): 3101-7

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Systemic Disease Management Systemic Disease Management 4 Several chronic medical conditions have been associated with an increased risk and/or progression of AMD 4

Managing these risk factors closely with a patient’s PCP or specialist is part of overall AMD management

• Diabetes • Obesity – Patients with diabetic retinopathy were at – A 32% increase in the risk of developing late AMD was noted significantly greater risk of subsequent development among obese individuals of AMD – Presence of diabetes predicted incident geographic atrophy in the Blue Mountains Eye Study • Cardiovascular Disease (CVD) – Studies have shown a variable link with several CVD outcomes • High Cholesterol § Coronary artery disease – Increasing levels of high-density lipoprotein cholesterol § Myocardial infarction was inversely related to incident late AMD § Angina – Elevated total/HDL cholesterol ratio predicted late – Drusen and atherosclerotic plaques also have a number of components in AMD common

99 QIAN-YU ZHANG, ET AL. INVEST. OPHTHALMOL. VIS. SCI. 2016;57(3):1276-1283. | PENNINGTON, K. L., & DEANGELIS, M. M. (2016). EYE AND VISION, 3(1). 100 HE, M.-S., ET AL, 41(10), 2202–2211. |29. TAN JSL, ET AL. OPHTHALMOLOGY. 2007;114(6):1143-1150.

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Make healthy shifts

Nutrient dense snacks replace High calorie snacks Fruit replaces fruit products with added sugars Whole grains replace refined grains Unsalted snacks replace snacks with added sugars Oils replace saturated fats No-sugar-added beverages replace sugar-added beverages

HTTPS://HEALTH.GOV/OUR-WORK/FOOD-NUTRITION/2015-2020-DIETARY-GUIDELINES/GUIDELINES/ ACCESSED OCTOBER 1, 2020

HTTPS://HEALTH.GOV/OUR-WORK/FOOD-NUTRITION/2015-2020-DIETARY-GUIDELINES/GUIDELINES/ ACCESSED OCTOBER 102 1, 2020

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5 Simple dietary changes everyone should make (from the American Psychological Association)

1 2 3 4 5

Eat one Limit your Make heart Pass on Consume healthy food extra the salt a healthy intake of swaps serving of sugar- fruits or shaker breakfast sweetened veggies *“Sugar is thebeverages* new tobacco.” Professor Susan Jebb, OBE, Oxford every day “Sugar is the greatest threat to our healthcare system” Aseem Malhotra, MBChE, MRCP, British Cardiologist

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Some more practical advice (three “food” sources to avoid) If it . . . • is refined, • comes in a box, • is white (ex., cauliflower), • comes with a pop top, Recommendations • contains high amounts of to reduce the risk of omega-6 fatty acids, Type 2 diabetes • doesn’t require at least a few minutes to prepare,

• Don’t eat It! Thomas Morrow, MD. http://www.rsa- al.gov/uploads/files/PEEHIP_Advisor_Feb_18_web.pd f. Accessed February 24, 2018

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Retinal Light Protection 5 Sui G-Y, et al. Br J Ophthalmol. 2013;97(4):389-394. | Pipis A, et al. Eur J Ophthalmol. September 2014 | Zhao, Zhi-Chun, et al. International Journal of Ophthalmology. 11(12): 1999–2003.

Chronic sunlight exposure increases the risk of incident AMD and its progression

Full-spectrum UV protection Monitoring progression and PLUS detecting change High Energy Visible Light (HEVL) / Blue Light filtering lenses Amsler Grid

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* The Amsler Grid is insufficient - poor sensitivity and specificity; especially in advanced disease

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States with only four letters • I hope that I have convinced you that beyond the impact on individual patients, AMD can be a significant burden on health-care resources • Iowa • Utah • Clinicians are aware that AMD is progressive and that we may be able • Mississippi to slow that trajectory • Tennessee • There are some recommendations that we can adopt that may • Alaska correlate with improved outcomes among patients diagnosed with • Hawaii dry AMD specifically following recommendations regarding lifestyle • Indiana choices and supplement recommendations. . . • Kansas how do we monitor AMD trajectory? • Alabama Early - AdaptDx Intermediate dry and Wet - Foresee

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THANK YOU

Stay safe Be smart [email protected]

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