Diabetic Retinopatathy Jay M. Haynie, OD, FAAO Financial Disclosure I have received honoraria or am on the advisory board for the following companies: Carl Zeiss Meditec Arctic DX Macula Risk Advanced Ocular Care Genentech USA USMA Lampa Advisory Executive Clinical Director Retina and Macula Specialists Jan. 28, 2008 -- The number of older Americans diagnosed with diabetes grew by nearly a quarter in the last decade, a rate that experts say threatens not only the health of the elderly but the viability of the nation's health care system. Type 2 diabetes is the most prevalent form of the disease, accounting for 90 to 95% of all diabetes cases in America AND is largely preventable according to the CDC. Although the vast majority of individuals with type 2 diabetes are adults, children and adolescents are increasingly at risk for the disease due to growing childhood weight problems and sedentary lifestyles. 1
Research suggests that 1 out of 3 adults has prediabetes. Of this group, 9 out of 10 don't know they have it. 29.1 million people in the United States have diabetes, but 8.1 million may be undiagnosed and unaware of their condition. About 1.4 million new cases of diabetes are diagnosed in United States every year. More than one in every 10 adults who are 20 years or older has diabetes. For seniors (65 years and older), that figure rises to more than one in four. Cases of diagnosed diabetes cost the United States an estimated $245 billion in 2012. This cost is expected to rise with the increasing diagnoses. The International Diabetes Federation reports that more than 400 million people were living with diabetes as of 2015. Prior estimations predicted 300 million by 2025. Either you have it or you don t. That's the message that the American Diabetes Association (ADA) is driving home to millions of people who believe they may be "borderline diabetic," or that their "sugar is just a bit high." What is diabetes? DM is a chronic disorder characterized by a lack of insulin or increased resistance to insulin Insulin is needed for proper uptake of glucose Clinical result is hyperglycemia retinopathy nephropathy neuropathy Diabetes: Magnitude of Complications Leading cause of blindness in working age adults Diabetic Retinopathy Stroke 2- to 4- fold increase in cardiovascular mortality and stroke Obesity Trends* Among U.S. Adults BRFSS, 1994 (*BMI 30, or ~ 30 lbs overweight for 5 4 person) Diabetic Nephropathy Leading cause of end-stage renal disease Cardiovascular Disease Diabetic Neuropathy Leading cause of non-traumatic lower extremity amputations No Data <10% 10% 14% 15% 19% 20% 24% 25% 2
New Diagnosis Criteria Panel of experts at ADA annual meeting are recommending A1C be used for diagnosis of diabetes Glycosolated hemoglobin Tells blood sugar control over 3 months normal range 4% to 6% What do the results of the Hemoglobin A1c mean.? HgbA1c BS Level HgbA1c BS Level 4 60 9 210 5 90 10 240 6 120 11 270 7 150 12 300 8 180 13 330 What do the results of the Hemoglobin A1c mean.? What is our role?? 3
- Classification of : Non Proliferative Mild Moderate Severe Very Severe Proliferative - Classification of : H/MA hemorrhage or microaneurysm VB venous beading IRMA intraretinal microvascular abnormalities NEO - neovascularization - Classification of : Mild Non Proliferative At least one microaneurysm Characteristics not met for more severe retinopathy - Classification of : Moderate Non Proliferative H/MA greater than standard photograph No. 2A and/or Cotton wool spots, VB, or IRMA present OCT Angiography (OCTA) Characteristics not met for more severe retinopathy 4
- Classification of : Severe Non Proliferative H/MA greater than standard photograph No. 2A in 4 quadrants or VB in 2 or more quadrants or IRMA greater than standard photograph No. 8A in at least 1 quadrant 4 2 1 RULE Characteristics not met for more severe retinopathy - Classification of : Very Severe Non Proliferative Two or more criteria of Severe NPDR No frank neovascularization - Classification of : H/MA s in 4 quadrants = Severe Non PDR 5
- Classification of : - Classification of : IRMA in 2 quadrants = Severe Non PDR H/MA s in 4 quadrants = Severe Non PDR IRMA in 2 quadrants = Severe Non PDR Rate of Progression to PDR 1 year 3 years Mild NPDR 5 % 14% Moderate NPDR 12-26 30-48 Severe NPDR 52 71 - Classification of : Proliferative Neovascularization of the disc (NVD) < Standard photo 10A (<0.25 0.33 disc area) Neovascularization elsewhere in the retina (NVE) without associated vitreous or pre-retinal hemorrhage Treatment: Clinically Significant Macular Edema Laser Photocoagulation is recommended for patients who meet criteria for CSME regardless of visual acuity. Laser Photocoagulation reduces the risk for moderate vision loss by 50%. Moderate vision loss is doubling the visual angle. 6
Treatment: Clinically Significant Macular Edema Despite the guidelines for treatment of CSME with laser photocoagulation, many patients are treated with intravitreal agents such as Avastin, Lucentis, Triesence and Eylea initially. Diabetic Macular Edema: Approved Pharmacologic Treatment Lucentis (Ranibizumab) Eylea (Aflibercept) Diabetic Macular Edema: Approved Pharmacologic Treatment Ozurdex (Dexamethasone Intravitreal Implant) Diabetic Macular Edema: FUTURE: Pharmacologic Treatment Iluvien (Fluocinolone Acetonide Implant) 36 month duration 80 % cataract 35% elevated IOP greater than 10mmHg (5% require glaucoma surgery) Treatment: Diabetic Macular Edema (antivegf) Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema (Protocol T) 7
Protocol T Ranibizimab was the first approved anti VEGF treatment option for diabetic macular edema (DME) and studies have shown it to be safe and efficacious and superior to focal/grid laser alone for patients with center involved DME. A concern is the cost per dose of ranibizumab and the need for multiple treatments over time. Protocol T Is there an alternative anti VEGF agent that might prove to be as efficacious, deliver equal or longer acting effects and cost substantially less. Bevacizumab and Afliberacept are the other options available for comparison. 660 adults in 89 clinical sites Protocol T - Ranibizumab 0.3 mg every 4weeks at baseline and up to every 4 weeks using defined re treatment criteria - Bevacizumab 1.25 mg every 4weeks at baseline and up to every 4 weeks using defined re treatment criteria - Afliberacept 2.0 mg every 4weeks at baseline and up to every 4 weeks using defined re treatment criteria Protocol T Primary Outcome Measures: Overall change in visual acuity measured at 1 year Change in VA measured from baseline to 1 year Baseline VA letter score <69 (20/50 or worse) Change in VA measured from baseline to 1 year Baseline VA letter score 78-69 (20/30 20/40) Protocol T Secondary Outcome Measures: (at 1 year) Overall change in OCT central subfield thickness Change in OCT central subfield thickness from baseline to 1 year Baseline VA letter score <69 Change in OCT central subfield thickness from baseline to 1 year Baseline VA letter score 78-69 Protocol T Secondary Outcome Measures: Overall change in retinal volume Total number of injections prior to one year Total number of laser treatments Eyes receiving 1 or more alternative treatments for DME other than laser 8
MEAN CHANGE IN VISUAL ACUITY LETTER SCORE MEAN CHANGE IN VISUAL ACUITY LETTER SCORE MEAN CHANGE IN VISUAL ACUITY LETTER SCORE MEAN CHANGE IN VISUAL ACUITY LETTER SCORE Protocol T 20 Mean Change in Visual Acuity Letter Score Baseline Visual Acuity 20/32 to 20/40 Results: Year 1 all three anti VEGF compounds improved acuity, on average, in patients with baseline acuity of 20/40 to 20/32 but Afliberacept was superior when baseline acuity was 20/50 or worse. 18 16 14 12 10 8 6 4 2 0 ~50% of Cohort ~+ 8 0 4 8 12 16 20 24 28 32 36 40 44 48 52 WEEKS Aflibercept Bevacizumab Ranibizumab 20 18 Mean Change in Visual Acuity Letter Score Baseline Visual Acuity 20/50 or Worse +19 Protocol T 16 14 ~ 50% of Cohort +14 Results: 12 10 8 6 4 2 0 +12 0 4 8 12 16 20 24 28 32 36 40 44 48 52 WEEKS Aflibercept Bevacizumab Ranibizumab Year 2 improved vision was again noted in all 3 groups with an average of half of the number of injections, decreased frequency of visits and a decrease in the need for focal/grid laser treatment. * P-values adjusted for baseline visual acuity and multiple comparisons Mean Change in Visual Acuity Over 2 Years Full Cohort Mean Change in Visual Acuity Over 2 Years Baseline Visual Acuity 20/50 or Worse 20 18 16 14 12 10 8 +13.3 +12.8 +11.2 +12.3 +9.7 +10.0 20 18 16 14 12 10 ~50% of Cohort +18.9 +14.2 +11.8 +18.1 +16.1 +13.3 6 8 4 6 2 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 WEEKS Aflibercept Bevacizumab Ranibizumab * P-values adjusted for baseline visual acuity and multiple comparisons 4 2 0 * P-values adjusted for baseline visual acuity and multiple comparisons 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 WEEKS Aflibercept Bevacizumab Ranibizumab 9
New description Diabetic Macular Edema: Diabetic Macular Edema: Clinical Trials Center Involved Macular Edema CSME has now been further characterized Center involved edema Non center involved edema Diabetic Macular Edema: Clinical Trials Non - Center Involved Macular Edema Treatment: Proliferative The Study showed that scatter laser PRP reduced the incidence of severe vision loss by up to 50 % in patients with Proliferative. Severe vision loss is < 5/200 Treatment: Proliferative Treatment: Proliferative 10
Treatment: Proliferative Proliferative - OCTA INSERT CLARUS IMAGE HERE OF PRP 55 year old man with Type I Diabetes 55 year old man with Type I Diabetes AngioPlex VRI slice confirms neovascularization (NVE) AngioPlex / FA images showing neovascularization (NVE) as well as the enlarged FAZ Proliferative - OCTA Even with treatment and resolution of macular edema some patients continue to have severe vision loss.. Driven by ischemia! 11
OCT angiography Zeiss AngioPlex Combination therapy has become standard for the treatment of diabetic retinopathy. Prolferative Retinopathy with marked non perfusion and NVE 1 Month status post AVASTIN with panretinal laser treatment. 3 Months status post AVASTIN with panretinal laser treatment. Vitreous Hemorrhage and Traction Retinal Detachments Despite best efforts to manage complications of diabetes in the office some patients require surgical intervention with Vitrectomy. 12
Vitreous Hemorrhage and Traction Retinal Detachments Traction Retinal Detachment 1 month s/p silicone oil Prompt Panretinal Photocoagulation Versus Ranibizumab+Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy (Protocol S) Ptotocol S Randomized Clinical Trial evaluated noninferiority of ranibizumab vs. panretinal photocoagulation (PRP) with a primary endpoint of mean change in visual acuity from baseline to 2 years. 203 eyes randomized to receive PRP 191 eyes received 0.5mg intravitreous ranibizumab at baseline and every 4 weeks based on re treatment protocol 13
Protocol S 2 Year results: Visual acuity improvement PRP group improvement in 0.2 letters 0.5 mg ranibizumab group 2.8 letters Protocol S 2 Year results: Peripheral VF loss and Vitrectomy PRP group 531 db loss and 15% needed surgery 0.5 mg ranibizumab group 213 db loss and 4 % Ranibizumab Approved in 2017 to treat ALL levels of Diabetic Retinopathy Type I Diabetes with Proliferative Retinopathy PRP laser treatment in 1990 Will this change what we do for patients with a chronic diabetic eye disease? Is it the right thing to do? Type I Diabetes with Proliferative Retinopathy PRP laser treatment in 1990 - OCTA Type I Diabetes with Proliferative Retinopathy PRP laser treatment in 1990 - OCTA 14
Type I Diabetes with Proliferative Retinopathy PRP laser treatment in 1990 - OCTA Although clinical trials have defined the standard of care for management of CSME and PDR..intravitreal agents like Avastin/Lucentis, Eylea and Steroids have rapidly become adjuncts to laser treatment and prior to Vitrectomy surgery. Avastin has also become a crucial component in the management of neovascular glaucoma by inducing regression of rubeosis within a few days. Referral Criteria: Non Proliferative Mild NPDR follow yearly Moderate NPDR follow q6 12 months Severe NPDR follow q4-6 months / REFER? Very Severe NPDR follow q3 months / REFER? ** Consider patient control of diabetes ** Consider success of therapy ** Consider risks for progression to PDR ** Consider personal comfort level Referral Criteria: Proliferative - Prompt referral for pan retinal photocoagulation based of the guidelines of the DRS. - If rubeosis is present Avastin + PRP should be initiated within 48 72 hours to prevent neovascular glaucoma. Referral Criteria: Diabetic Macular Edema Referral Criteria: Diabetic Macular Edema - Follow the guidelines of the ETDRS when considering the referral?? - Most retina surgeons will treat center involved diabetic macular edema Center versus non center involved edema.. 15
JayH@retina-macula.com 16