A Systematic Approach to Diabetic Photo Reading

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1 A Systematic Approach to Diabetic Photo Reading Jacqueline Theis, OD, FAAO Please silence all mobile devices and remove items from chairs so others can sit. Unauthorized recording of this session is prohibited.

2 Disclosure Statement: C. Light Technologies Clinical Research Consultant, NIH SBIR

3 Objectives 1. Understand the pathophysiology of diabetic retinopathy to understand pattern recognition in grading diabetic screening photos 2. Describe the clinical practice guidelines for monitoring versus referral of diabetic retinopathy when it is and is not vision threatening 3. Increase the comfort level of practitioners in reading diabetic photos by reviewing numerous photos of various diabetic retinopathy levels in an interactive format

4 The Statistics 30.3 million US adults have Diabetes (25% don t know they have it) In the last 20 years, the number of adults diagnosed with DM has more than tripled (due to population aging and obesity) Diabetes is the #1 cause of adult-onset blindness in the US Types Type 1 5% of diabetes Cellular-mediated autoimmune destruction of beta cells in the pancreas à severe/absolute insulin deficiency Type 2 95% of diabetes cases Range of disease from insulin resistance with relative insulin deficiency Gestational Prediabetes 84.1 million adults (90% don t know they have it) Centers for Disease Control and Prevention. National Diabetes Statistics Report, Atlanta, GO: Centers for Disease Control and Prevention, US Department of Health and Human Services;2017.

5 Age-adjusted Prevalence of Obesity and Diagnosed Diabetes Among US Adults Obesity (BMI 30 kg/m 2 ) No Data <14.0% 14.0% 17.9% 18.0% 21.9% 22.0% 25.9% > 26.0% Diabetes No Data <4.5% 4.5% 5.9% 6.0% 7.4% 7.5% 8.9% >9.0% CDC s Division of Diabetes Translation. United States Surveillance System available at

6 Number and Percentage of U.S. Population with Diagnosed Diabetes, Percentage with Diabetes Percentage with Diabetes Number with Diabetes Number with Diabetes (Millions) Year 0 CDC s Division of Diabetes Translation. United States Diabetes Surveillance System available at

7 Epidemiology of Diabetic Retinopathy For all adults with diabetes aged % (4.2 million people) in the US have diabetic retinopathy 4.4% (700,000 people) have vision-threatening diabetic retinopathy (VTDR) Projected prevalence by million people in the US will have diabetic retinopathy 1.34 million people with VTDR Klein BE. Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol. 2007;14: Kempen JH, O Colmain BJ, Leske MC, et al. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004;122: Zhang X, Saaddine JB, Chou CF, et al. Prevalence of diabetic retinopathy in the United states, JAMA 2010;304:

8 Retinal Anatomy

9 Macular OCT

10 MAC OCT + Retinal Anatomy Photoreceptor synapses Photoreceptor cell bodies Inner Photoreceptor Segment Inner/Outer Photoreceptor Segments Outer Photoreceptor Segments PR interdigitation with RPE

11 Image from Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Progress in Retinal and Eye Research. 2012;31: Drawngs by Dave Schumick from Anand-Apte and Hollyfield 2009.

12 Image from Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Progress in Retinal and Eye Research. 2012;31: Drawngs by Dave Schumick from Anand-Apte and Hollyfield 2009.

13 Retinal Vasculature Dot Hemes Flame Hemes Superficial capillary Superficial capillary Deep Capillary Deep Capillary Choroid Choroid

14 Anatomy of retinal capillaries Non-fenestrated endothelial cells Cells linked by tight junctions and adherens junctions = inner Blood Retinal Barrier (ibrb) Protects retina from toxic molecules in blood circulation Pericytes Provide structural support Regulates expression of tight junction proteins Modulates endothelial cell function Glia (Muller cells, astrocytes) Provide metabolic support to neurons Maintain ibrb, needed for retinal homeostasis Immune Cells (microglia) Lechner J, O Leary OE, Stitt AW. The pathology associated with diabetic retinopathy. Vision Research. 139 (2017): 7-14

15 Vascular Complications in Diabetes Atherosclerosisà cardiovascular disease and impaired life expectancy Diabetic nephropathyà endstage renal disease Diabetic retinopathyà blindness Picture from Rask-Madsen C, King GL. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metabolism. 2013;17:20-33

16 Pathophysiology of Diabetic Retinopathy High glucose à increased pericyte apoptosis (lose vascular autoregulation) à nutrient/oxygen deprivation to inner retina (poor blood flow) Can occur in retinopathy-free clinical appearance àmicrovascular damage ibrb breakdown à increased inflammation and oxiddationà MORE vascular dysfunction àretinal capillary non-perfusion (vasodegeneration)à MORE retinal ischemia and hypoxiaà Excessive vasopermeability in the retina à retinal thickening/edema Upregulation of VEGFà neovascularization of disc, retina, iris and angle

17 Pathophysiology of Neovascularization (PDR) Capillary non-perfusion àretinal ischemiaà VEGFà NV NV occurs at the interface between perfused and non-perfused retina NV often grows on the surface of the retina and penetrates the ILM into the vitreous NV vessels are fenestrated (brittle, leaky) à vitreous hemorrhage Repeat vitreous hemorrhage à gliosis and fibrovascular scar formation Fibrous tissue contractionàtractional RD

18 What Causes Visual Loss in Diabetic Retinopathy? Macular edema Ischemic maculopathy Vitreous hemorrhage Retinal detachment Neovascular glaucoma

19 Clinical Findings in Diabetic Retinopathy

20 DR: Microaneurysms (MA) Loss of pericytes and/or glial attachments on capillary blood vessel wall à ballooning of capillary vessel wall Red dot <125um (1/12 the diameter of an average optic disc OR approx. the width of an average major vein at the disc margin) and has sharp margins ETDRS#10: Grading diabetic retinopathy from stereoscopic color fundus photographs an extension of the modified Airlie House Classification. Ophthalmol. 1991;98:

21 DR: Hemorrhages Any spot larger than a MA Red spot of MA size with irregular margins Flame hemorrhages Leakage of fluid from MA in superficial capillary bed (localized edema) Dot hemorrhages Leakage of fluid from MA in deep capillary bed (localized edema) Blot Hemorrhages Leakage of fluid from clusters of occluded capillaries Often occur with cotton wool spots

22 DR: Cotton Wool Spots Disturbed axoplasmic flow due to an obstruction of neuronal blood flow (infarction) causes local death of the tissue and a localized superficial swelling in the retinal nerve fiber layer Round or oval, white, pale yellow-white or greyish-white, with feathery edges, frequently with striations parallel to the nerve fibers

23 DR: Intraretinal Microvascular Anomalies (IRMA) Local ischemia leads to capillary/ vascular remodeling causing large tortuous vessels NOT NEW VESSELS Anomaly of innate vasculature

24 Venous Abnormalities Venous Beading (VB) Localized increases in venous caliber caused by ischemia Venous Narrowing Venous Loops

25 DR: Hard Exudates (HE) Hard lipoprotein deposits that remain when blood gets reabsorbed in the retina Small white or yellowish-white deposits with sharp margins. Often have a slightly waxy or glistening appearance Usually located in the outer retina, may be more superficial

26 Drusen vs Hard Exudate Drusen Deposits at or anterior to Bruch s membrane associated with thinning or hypopigmentation of the overlying RPE Appear as deep, yellowish-white dots, sometimes circumscribed by a thin line of pigment Location Drusen Deep in the retina at level of RPE Scattered diffusely or clustered near the macula Hard Exudates Superficial, in outer or middle layers of the retina Near MA or edge of retinal edema Shape Round Irregular Appearance Dull Waxy, shiny Halo/border of pigment

27 DR: Neovascularization New vessels grown in response to ischemia/vegf NVD- neovascularization on or within 1DD of optic disc margin NVE new vessels on the surface of the retina or in the vitreous cavity NVI new vessels on the iris NVA new vessels on the angle

28 PDR + Fibrous proliferation Fibrous tissue strands or sheets of thickened posterior hyaloid surface FPE (elsewhere) or FPD (disc) Preretinal hemorrhage Boat-shaped hemorrhage and/or round, oval, or linear patches of hemorrhage just anterior to the retina or under its internal limiting member Vitreous hemorrhage Hemorrhage further forward in the vitreous cavity than PRH Retinal elevation Retinal detachment, retinoschisis, or elevation of large retinal vessel Prior laser scars Once PDR, always PDR Diabetic papillitis

29 Clinically Significant Macular Edema (CSME) Retinal thickening that involves or threatens the center of the macula (even if visual acuity is not yet reduced) According to ETDRS Thickening of the retina at or within 500um of the center of the macula (1DD) Hard exudates at or within 500um of the center of the macula, if associated with thickening of adjacent retina (not residual hard exudates remaining after disappearance of retinal thickening) A zone or zones of retinal thickening 1 disc area or larger, and part of which is within 1 DD of the center of the macula Defined because CSME responds to treatment significantly, non- CSME does not Keep in mind: ETDRS was published before OCT was around

30 International Clinical Disease Severity Scales Diabetic Retinopathy Disease Severity Scale Disease Severity Level No DR Mild NPDR Moderate NPDR Severe NPDR PDR Findings No abnormalities MAs only More than mild, less than severe. MAs + Hemes/CWS/IRMA<8A/ VB<6A 4:2:1 Rule (any of): Hemes>2A in 4 quadrants VB> 6A in 2 quadrants IRMA>8A in 1 quadrant One or more of the following: NV, vitreous/preretinal heme, tractional RD Diabetic Macular Edema Disease Severity Scale Disease Severity Level Mild DME Moderate DME Severe DME Findings Retinal thickening or HE in posterior pole but distant from center of the macula Retinal thickening or HE approaching the center of macula but not involving the center Retinal thickening or HE involving the center of the macula Wilkinson CP, Ferris FL, Klein RE, Lee PP, Agardh CD, Davis M, Dills D, Kampik A, Pararajasegaram R, Verdaguer JT. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmol. 2003:110:

31 Standard Photograph 2A

32 Standard Photograph 8A

33 Standard Photograph 6B

34 Ophthalmological Treatment of DR Treatment Modality Indications Evidence Anti-VEGF injections Center-involving DME PDR Diabetic Retinopathy Clinical Research Network (DRCR.net) Ranibizumab for Edema of the Macula in Diabetes Study (READ-2) Study of Ranibizumab Injection in Subjects with CSDME with Central Involvement Secondary to Diabetes Mellitus (RISE and RIDE) Bevacizumab or Laser Therapy (BOLT) Study DME and VEGF-Trap-Eye: Investigation of clinical impact (DA VINCI) Study Focal laser photocoagulation Panretinal photocoagulation Vitrectomy Non-center involving DME PDR -Severe PDR -Severe vitreous hemorrhage -Tractional RD Early Treatment of Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Study (DRS) Diabetic Retinopathy Vitrectomy Study (DRVS)

35 Optometric Treatment of DR Communicate findings and level of retinopathy to PCP Intensive treatment of glucose (Hba1c,6.0%) delays onset and slows progression of DR (but does not prevent DR completely) DCCT After 6 years Intensive blood glucose control slowed microvascular complications of Retinopathy by 76% (if no retinopathy present at baseline) Retinopathy by 54% (if some retinopathy at baseline) Neuropathy by 60% Nephropathy by 50% Takes at least 36 months for significant difference Normoglycemic re-entry (slight worsening of retinopathy) for first 18 months possible Intensive blood pressure control reduces the risk of DR by 34% - UKPDS Once retinopathy is present, glycemic control is best predictor of progression od retinopathy Screen/diagnose level of diabetic retinopathy to refer for prompt ophthalmological treatment

36 Risk Factors for DR/Progression of DR Duration of DM Severity of hyperglycemia Hypertension Current Smoker

37 Screening Guidelines for Non-Proliferative Diabetic Retinopathy Level of NPDR No NPDR Type 1 No NPDR Type 2 Mild NPDR Moderate NPDR no DME Moderate NPDR with DME but not CSME Severe NPDR Follow Up Annually beginning 5 years after onset of the disease Prompt exam at diagnosis then every 1-3 years after Every 1-3 years Every 6 months Every 3-4 months Every 3 months Gestational DM DM1/2 that becomes pregnant Do not require eye exam during pregnancy Do not appear to be at an increased risk of developing DR during pregnancy Exam early in the course of pregnancy The DCCT/EDIC Research Group. Frequency of evidence-based screening for retinopathy in type 1 diabetes. N Engl J Med. 2017;676(16): AAO 2014 preferred practice pattern

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40 Pearl 1: You need to Zoom You need good screen resolution You may need to turn off your room lights

41 Case A - OD 56yo DM2 x 10 years HbA1c 7.3 Full View

42 Case A - OD 56yo DM2 x 10 years HbA1c 7.3 Zoom ONH +/- NVD +/-NVE +/-Other optic neuropathy

43 Case A - OD 56yo DM2 x 10 years HbA1c 7.3 Zoom Macula +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

44 Case A - OD 56yo DM2 x 10 years HbA1c 7.3 Zoom Sup. Arcades +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

45 Case A - OD 56yo DM2 x 10 years HbA1c 7.3 Zoom Sup. Arcades +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

46 Case A - OD 56yo DM2 x 10 years HbA1c 7.3 Zoom Inf. Arcades +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

47 Case A - OD 56yo DM2 x 10 years HbA1c 7.3 Zoom Inf. Arcades +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

48 Case A - OD 56yo DM2 x 10 years HbA1c 7.3 Severe? 4 Hemes/Mas 2 VB 1 IRMA Summary: +Hemes>10 +Hex Dx: Moderate NPDR

49 Why Photos are important

50 Case A - OD 56yo DM2 x 10 years HbA1c 7.3 Full View

51 Case A - OD 56yo DM2 x 10 years HbA1c 7.3 Full View

52 Case A - OS 56yo DM2 x 10 years HbA1c 7.3 Full View

53 Case A - OS 56yo DM2 x 10 years HbA1c 7.3 Zoom ONH +/- NVD +/-NVE +/-Other optic neuropathy

54 Case A - OS 56yo DM2 x 10 years HbA1c 7.3 Zoom Macula +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

55 Case A - OS 56yo DM2 x 10 years HbA1c 7.3 Zoom Sup. Arcades +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

56 Case A - OS 56yo DM2 x 10 years HbA1c 7.3 Zoom Sup. Arcades +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

57 Case A - OS 56yo DM2 x 10 years HbA1c 7.3 Zoom Sup. Arcades +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

58 Case A - OS 56yo DM2 x 10 years HbA1c 7.3 Zoom Inf. Arcades +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE Summary: +Hemes>10 +Hex +CWS Dx: Moderate NPDR

59 Pearl 2: You need to adapt a rote approach to evaluating the photo

60 Case B OD 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

61 Case B OD 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2 Zoom Macula +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

62 Case B OS 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

63 Case B OD 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2 Zoom Macula +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

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65 Case C OD 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2

66 Case C OD 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2

67 Case C OD 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2

68 Case C OS 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2

69 Case C OS 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2

70 Case C OS 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2

71 Case C OS 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2

72 Case C OS 35yo DM1 x 17 years HbA1c 9.0 VA: 20/20-2

73 Pearl 3: Always assume that there is edema when you see hard exudates Pearl 4: Make sure you scroll through the entire macular scan as edema may not be captured in the global summary scan

74 Case C OD 61yo DM2 x 8 years HbA1c Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

75 Case C OD 61yo DM2 x 8 years HbA1c Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

76 Case C OD 61yo DM2 x 8 years HbA1c 8.3 VA: 20/ Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

77 Case C OS 61yo DM2 x 8 years HbA1c Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

78 Case C OS 61yo DM2 x 8 years HbA1c Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

79 Case C OS 61yo DM2 x 8 years HbA1c 8.3 VA: 20/ Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

80 Case C OD 61yo DM2 x 8 years HbA1c 8.3 VA: 20/ Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

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83 Case C OS 61yo DM2 x 8 years HbA1c 8.3 VA: 20/ Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

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86 Pearl 5: Exudates and surrounding edema can be reabsorbed so while you assume edema when you see exudates on the photo sometimes you will find exudates WITHOUT edema

87 Case D OD 67yo DM2 w CKD stage 3 HbA1c 8.3 VA: 20/25-2 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

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89 Never underestimate the presence of hemorrhages near the macula!

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92 Case D OS 67yo DM2 w CKD stage 3 HbA1c 8.3 VA: 20/50 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

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94 ERM with Pseudohole

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102 NVE

103 Pearl 6: Use the OCT and the photo to better understand the pathology. On dilated exam with a 3D view you would see the elevation missed on the fundus photo

104 Case E OD 67yo DM2 x 8 years HbA1c 7.3 VA: 20/20-2 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

105 Case E OD 67yo DM2 x 8 years HbA1c 7.3 VA: 20/20-2 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

106 Case F OD 67yo DM2 x 8 years HbA1c 7.3 VA: 20/20-2 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

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108 Case F OD 65yo DM2 x 12+ years HbA1c 9.4 VA:? Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

109 Case G OD 65yo DM2 x 12+ years HbA1c 9.4 VA:? Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

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122 Case G OD 65yo DM2 x? years HbA1c 9.3 VA: 20/30 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

123 Case H OD 65yo DM2 x? years HbA1c 9.3 VA: 20/30 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

124 Case H OD 65yo DM2 x? years HbA1c 9.3 VA: 20/30 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE Severe? 4 Hemes 2 VB 1 IRMA

125 Case H OD 65yo DM2 x? years HbA1c 9.3 VA: 20/30 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

126 Case H OD 65yo DM2 x? years HbA1c 9.3 VA: 20/30 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

127 Case H OD 65yo DM2 x? years HbA1c 9.3 VA: 20/30 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

128 Case H OD 65yo DM2 x? years HbA1c 9.3 VA: 20/30 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

129 Pearl 7: Some retinas can burn out and not look severe- but actually be very ischemic and have NV Be ware of the retinopathy that lies outside the single fundus view.

130 Case I OS 65yo DM2 x? years HbA1c 9.3 VA: 20/30 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

131 Case I OS 65yo DM2 x? years HbA1c 9.3 VA: 20/30 Full View +/-MA or Hemes +/- HEX +/- CWS +/- thickening +/- irma +/- VB +/-NVE

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133 Please remember to complete your session evaluations on the Academy.18 meeting app Tweet about this session using the official meeting hashtag #Academy18

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