1、Neil Bressler,MDEditor-in-ChiefJAMA OphthalmologyProfessor of OphthalmologyJohns Hopkins School of MedicineWhy the Eye:Advances in Eyecare and the Impact on the Patient Keynote PresentationNeil M.Bressler,MD*The James P.Gills Professor of OphthalmologyRetina Division(Chief:2005-2018)Wilmer Eye Insti

2、tuteJohns Hopkins University School of Medicine&Hospital Baltimore,MDEditor in Chief,JAMA Ophthalmology*Participation by Dr.N.Bressler in this activity does not constitute or imply endorsement by the Johns Hopkins University,the Johns Hopkins Hospital,or the Johns Hopkins Health System,nor by the DR

3、CR Network or JAMA OphthalmologyWhy the Eye:Advances in Eyecare and the Impact on the PatientFinancial and Other Disclosures*Data from IRB-approved human research is presented3I have the following financial interests or relationships to disclose:DisclosureAMA JAMA Ophthalmology*Editor-in-ChiefContra

4、ct from AMA*Bayer Healthcare Pharmaceuticals Inc.Grant Support to JHU*BiogenGrant support to JHU*Boerhinger IngelheimGrant support to JHU*FDA:Chair,Ophthalmic Devices PanelHonorarium from FDA*Genentech(Roche)Grant Support to JHU*RegeneronGrant Support to JHU*Samsung BioepisGrant Support to JHU*EMMES

5、 Company,LLC Chair:Data and Safety Monitoring Committee for The National Eye Institute Intramural ProgramContract from EMMES Company,LLC*Participation by Dr.Neil Bressler in this activity does not constitute or imply endorsement by the Johns Hopkins University,the Johns Hopkins Hospital,or the Johns

6、 Hopkins Health System,nor JAMA Ophthalmology*AMA=American Medical Association;FDA=Food and Drug Administration;JHU=Johns Hopkins University School of Medicine4Why the Eye:Advances in Eyecare and the Impact on the PatientMany Americans Rate Losing Eyesight as Having Greatest Impact in Daily LifeOn a

7、 scale of 1 to 10,with 1 having the least impact and 10 having the greatestimpact on your daily life,how would you rate:losing your eyesightSource:A Research!America poll of U.S.adults conducted in partnership with Zogby Analytics with support from Research to Prevent Blindness and the Alliance For

8、Eye and Vision Research,August 2014.Non-HispanicWhiteAsianHispanicAfrican-American49%43%38%57%1%3%3%3%2%3%4%3%7%9%5%10(Greatest)51(Least)Not SureBlindness Ranked High with Other Conditions Among All GroupsNon-HispanicWhiteAsianHispanicAfrican-American20%15%15%18%19%18%22%13%7%6%9%17%24%12%11%8%21%36

9、%31%30%BlindnessCancerAIDS/HIVAlzheimersNot sureSource:A Research!America poll of U.S.adults conducted in partnership with Zogby Analytics with support from Research to Prevent Blindness and the Alliance For Eye and Vision Research,August 2014.Which of the following diseases or ailments is the worst

10、 that could happen to you?How Does Vision Loss Compare with Other Health Problems?Ocular Disease Utility Value*Systemic Health State ValueNegligible visual loss(20/20-20/25)0.88Breast cancer,after radiotherapyMyocardial infarction0.890.87Minimal visual loss(20/30-20/50)0.81Colon cancer,poor prognosi

11、sAIDS0.800.79Moderate visual loss(20/60-20/100)0.72Stroke,moderateHome dialysis for 8 years0.730.72Severe visual loss(20/200-No Light Perception)0.61Tuberculosis:hospitalized for 3 mosUlcerative colitis,before surgery0.600.58Adapted from Brown MM,et al.Ophthalmology.2003;110:1076-1081,2003 with perm

12、ission from the American Academy of Ophthalmology.*Based on visual acuity in the better-seeing eye.How Does Vision Loss Impact Quality of Life?Mobility,both ambulatory and driving1Recognition of landmarks,street signs Reading and related close work1Activities of daily living(cooking,shopping,check w

13、riting,etc)Self Care Abilities2Reading of medicine bottles,nutritional labelsPreparing insulin injections,glucose testing Social participation1,2 Feelings of vulnerability,emotional distressDependence on others for transportation 1.Lennie P,Van Hemel SB,eds.Visual Impairments:Determining Eligibility

14、 for Social Benefits.National Academy of Sciences.2002.2.Coyne KS,et al.Family Practice.2004;21:447-453.Three Leading Causes of Blindness in the United States(and much of the Rest of the World)Diabetic retinopathy Age-related macular degeneration GlaucomaNormal EyeCorneaLensScleraChoroidRetinaVitreo

15、usRetinaVitreousPosterior Segment of Eye:Posterior StructuresVitreous&RetinaPathogenesis of Diabetic Retinopathy High blood sugar levels affect inner retinal capillaries,resulting in:Loss of pericytes(structural/functional support to capillary cells)Thickening of basement membrane(supporting structu

16、re)of endothelial(capillary)cells Pathophysiologic consequences:Leakage of blood vessels=diabetic macular edema Closure of retinal capillaries=proliferative diabetic retinopathyConsequences of Leakage of Capillaries:Diabetic Macular Edema Thickening of macula from intercellular fluid accumulation wi

17、thin retina Fluid leaks from microaneurysms and telangiectasia(dilation and toruosity of pre-existing capillaries)Fluorescein Angiography of Diabetic Macular Edema30 seconds after intravenous fluorescein injectionFluorescein Angiography of Diabetic Macular Edema6 minutes after intravenous fluorescei

18、n injectionVisual acuity=20/63Optical Coherence Tomography(OCT)Central subfield thickness=462 micronsDiabetic Macular EdemaNeed to identify the 93 million individuals with DR,including 21 million with DME,from those without DR2Need to identify the 21 million of individuals who develop DME before vis

19、ion loss has occurred to optimize intervening with treatment before substantial vision loss has occurred422 millionAdults living with diabetes in 2014,globally1DME,diabetic macular edema;DR,diabetic retinopathy1.Global Report of Diabetes.WHO.2016;2.Yau JW et al.Diabetes Care.2012 Mar;35(3):556-64.21

20、 millionNumber of diabetic patients worldwide with some form of DME21stchallenge2ndchallengeMagnitude of Public Health Problem from Diabetic Retinopathy,including Diabetic Macular Edema18Magnitude of Public Health Problem from Diabetic Retinopathy,including Diabetic Macular EdemaJAMA Ophthalmol.Publ

21、ished online June 15,2023.doi:10.1001/jamaophthalmol.2023.228919Magnitude of U.S.Public Health Problem from Diabetic Retinopathy,including Diabetic Macular Edema20Magnitude of U.S.Public Health Problem from Diabetic Retinopathy,including Diabetic Macular Edema21Magnitude of U.S.Public Health Problem

22、 from Vision Threatening Diabetic Retinopathy(including Diabetic Macular Edema,Severe Non-Proliferative or Proliferative Diabetic Retinopathy)Consequences of Leakage of Capillaries:Macular Edema Chronic edema associated with loss of retina tissue and subsequent vision loss 1986:Focal/grid laser phot

23、ocoagulation to thickening can reduce risk of vision loss from 30%over 3 years to 15%Lipid2010:Periodic Injection of Anti-VEGF Agent into Middle Cavity of Eye Superior to LaserDRCR Retina Network Protocol I:Mean Change in Visual Acuity(Letters)*23011048 12 16 20 24 28 32 36 40 44 48 52 56

24、 60 64 68 72 76 80 84 88 92 96100104Sham+promptlaserRanibizumab+prompt laserRanibizumab+deferred laser*Values that were 30 letters were assigned a value of 30P-values for difference in mean change in visual acuity from sham+prompt laser at the 52-week visit:ranibizumab+prompt laser 0.001;ranibizumab

25、+deferred laser 40 years)37Magnitude of Public Health Problem from Late Age-related Macular Degeneration(40 years&older)Approximately 15%(or 240 million people)have the intermediate stage of AMD,typically large drusen without symptoms need to identify to consider dietary supplements such as that use

26、d in AREDS1.6billionNumber of people over the age of 65 in 2050.11stchallengeAMD,age-related macular degeneration1.He W et al.An Aging World 2015.NIH Census Bureau.2.Rudnicka et al.Am J Ophthalmol2015;160(1):8593.Magnitude of Public Health Problem in Age-related Macular DegenerationAge-related Macul

27、ar Degeneration(AMD)Intermediate Stage:Extensive Medium or Large-Sized DrusenBasement membrane thickens&extensive medium or large-sized drusen become apparentIntermediate Stage of AMD by Treatment Group30%20%10%0%40%0Years1234567PlaceboAntioxidantsZincAntioxidants+ZincP vs.A+Z P 0.01 P vs.Z P 0.0120

28、%28%EstimatedProbabilityNumber at Risk for Advanced AMDC.Monocular Advanced AMD(NV&Central GA)961,214A.Intermediate AMD Monocular 4,818,074B.Intermediate AMD Binocular 2,266,2472003:Estimated#At Risk For Advanced AMDTotal at Risk8,045,535:double that in 202359,266,437(120 million in 2023)Total Age 5

29、5 or Older(U.S.)2003:Estimated Progression RateNo Treatment(5-Year Rate):Expected Progression to Advanced AMD:6.3%of 4.8 Million(Monocular Intermediate AMD)and 26.4%of 2.3 Million(Binocular Intermediate AMD)and 43.0%of 0.96 Million(Monocular Advanced AMD)1,315,150 Will Develop Advanced AMDTotal Prog

30、ression if No Treatment:Estimated Number Potentially Saved from Advanced AMD Assuming 25%Treatment EffectOver 5-Year PeriodPublic Health Impact in 2003328,788 Persons(double that in 2023)2005:ANCHOR:Monthly Fixed Dosing:Loss of 15 Letters From Baseline at 12 and 24 Months94%96%90%90%66%64%0204060801

31、00%of patients Ranibizumab 0.3 mg(n=140)Ranibizumab 0.5 mg(n=139)PDT(n=143)1-year outcomes12-year outcomes2*P.001 vs PDT;P.001 vs PDT 1.Brown et al.N Engl J Med.2006;355:1432.2.Brown et al.Ophthalmology 2009;116:5765.ANCHOR:Monthly Fixed Dosing:Gain of 15 Letters From Baseline at 12 and 24 Months 36

32、%40%34%41%6%6%020406080100%of patients 1-year outcomes12-year outcomes2Ranibizumab 0.3 mg(n=140)Ranibizumab 0.5 mg(n=139)PDT(n=143)*P.001 vs PDT;P.001 vs PDT 1.Brown et al.N Engl J Med.2006;355:1432.2.Brown et al.Ophthalmology 2009;116:5765.Similar outcomes with monthly aflibercept(VIEW 1&2)or month

33、ly bevacizumab(CATT)for at least 2 years=24 visits&24 injectionsVisual acuityTimeBaseline VA predicts outcomes at Year 1:CATT subgroup analysis78695839Mean VA at 12 months(letter score)Baseline VA(study eye)20/2520/8020/10020/16020/25020/40n=397n=414n=223n=71Eyes that begin at 20/25 to 20/40 have th

34、e best mean VA at 1 year1Similar stratification of response by baseline VA is also observed at 2 and 5 years2,3Early detection is critical to maintain visual functionCATT,Comparison of Age-Related Macular Degeneration Treatments Trials;VA,visual acuity.1.Ying G-S et al.Ophthalmology 2013;120(1):1221

35、29;2.Lee AY et al.Br J Ophthalmology 2015;99:10451050;3.Gillies MC et al.Ophthalmology 2015;122:18371845.Neovascular Age-related Macular Degeneration:Potential Next Steps Home monitoring:Identify who over age 50 has intermediate stage of AMD Consider dietary supplements such as those used in AREDS E

36、valuate for asymptomatic progression to neovascular AMD each year potentially supplemented with OCT exam Continue home monitoring to detect neovascular AMD Managing neovascular AMD If recent disease progression,typically initiate anti-VEGF therapy Try to identify CNV when visual acuity loss first oc

37、curs Frequent monitoring and frequent injections likely needed for mostApproximately 15%(or 240 million people)have the intermediate stage of AMD,typically large drusen without symptoms need to identify to consider dietary supplements such as that used in AREDSNeed to identify when neovascular form

38、begins,before substantial visual acuity loss has occurred1.6billion148,000Number of people over the age of 65 in 2050.1Number of new cases of neovascular AMD per year(US)21stchallenge2ndchallengeAMD,age-related macular degeneration1.He W et al.An Aging World 2015.NIH Census Bureau.2.Rudnicka et al.A

39、m J Ophthalmol2015;160(1):8593.Magnitude of Public Health Problem in Neovascular AMDHome-based Monitoring May Provide A Solution To The Delay In Detection And Treatment OCT,optical coherence tomography;VA,visual acuity.1.Bolster NM et al.J Diabetes Sci Technol 2015;10:318324;2.Kim TN et al.Transl Vi

40、s Sci Technol 2018;7(5):21;3.Brady CJ et al.JAMA 2015;314:26822683;4.Tofigh S et al.Eye(Lond)2015;29:14641468;5.Keane PA et al.Clin Ophthalmol 2015;9:353366.6.Paul W et al.JAMA Ophthalmol Published on line Jun 8,2023 Monocular vision testing while reading may provide one solutionPatient can cover on

41、e eye while reading and repeat while covering the opposite eye In addition,various tests and tools,including home-based vision or perimetry or OCT testing,may become more widely available to assist patients with monitoring their vision at home including:Smartphone-based fundus imaging1,2 Smartphone-

42、based applications for:oVisual acuity testing3,4 oShape discrimination hyperacuity5 Smartphone-based visual acuity determination from fundus image650Managing Diabetic Retinopathy and Age-related Macular DegenerationCan we determine the best-corrected visual acuity from AI analysis of the fundus imag

43、e?Might such AI information reduce the need for best-corrected visual acuity measurements in the clinic?Might such AI information through home monitoring of fundus images potentially detect onset of diabetic macular edema or age-related macular degeneration for which treatment should be considered?5

44、1Paul W,Burlina P,Mocharla R,et al.Accuracy of Artificial Intelligence in Estimating Best-Corrected Visual Acuity From Fundus Photographs in Eyes With Diabetic Macular Edema.JAMA Ophthalmol.Published online June 08,2023.52Paul W,Burlina P,Mocharla R,et al.Accuracy of Artificial Intelligence in Estim

45、ating Best-Corrected Visual Acuity From Fundus Photographs in Eyes With Diabetic Macular Edema.JAMA Ophthalmol.Published online June 08,2023.Next Steps:2023/2024(1)Macular Degeneration;(2)Clinical Practice Setting53Potential Next Steps:202554 Blindness is perceived as one of the worst things that ca

46、n happen to us Major causes of blindness in U.S.and much of the world:Diabetic retinopathyAge-related macular degenerationOpen angle glaucoma Other causes of blindness also have a substantial affect on ones quality of life Access to eye care across all socioeconomic groups is critical:Early detectio

47、n or prevention:more likely better vision outcomesHome monitoring of visual acuity or fundus images or both with AI may help address the magnitude of the problem Potential for improved ways of diagnosing,managing and preventing vision loss looks brightWhy the Eye:Advances in Eyecare and the Impact on the Patient