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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 -Pasteur 1 2 Disclaimer “Half of what you'll learn during training will be shown to be either dead wrong or out-of-date within 5 years ; How important is …the trouble is that nobody can tell you which half.”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) 3 4 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 5 6 1 6/7/21 February was established AMD awareness month in 2008 by Prevent Blindness https://nei.nih.gov/eyedata/amd 7 8 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 9 10 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 11 11 12 2 6/7/21 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. 13 14 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 15 16 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 17 18 3 6/7/21 Underdiagnosis of early AMD 19 20 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 21 22 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) 23 24 4 6/7/21 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 25 26 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 27 28 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. 29 30 5 6/7/21 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 31 32 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 33 34 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, </= 10 yrs) • History of MI SOURCES: HTTPS://WWW.CDC.GOV/CANCER/USCS/PUBLIC-USE/INDEX.HTM?CDC_AA_REFVAL=HTTPS%3A%2F%2FWWW.CDC.GOV%2FCANCER%2FNPCR%2FPUBLIC-USE%2FINDEX.HTM | 36 HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC5178091/PDF/40662_2016_ARTICLE_63.PDF | HTTPS://WWW.TOUCHOPHTHALMOLOGY.COM/ECONOMIC-IMPACT-OF-PROGRESSION-OF-AGE-RELATED-MACULAR- DEGENERATION/ 35 36 6 6/7/21 Why are mammograms performed? EARLIEST IDENTIFICATION OF AMD What you can’t see may be harmful! 37 38 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. 39 40 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 7 6/7/21 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. 43 44 What do you notice about this pristine looKing retina? 45 46 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.
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