Dr Dianne Sharp Ophthalmologist Retina Specialists, Parnell Greenlane Clinical Centre

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Clifford Moody
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1 Dr Dianne Sharp Ophthalmologist Retina Specialists, Parnell Greenlane Clinical Centre 11:00-11:55 WS #115: The Revolution in Macular Degeneration Management 12:05-13:00 WS #127: The Revolution in Macular Degeneration Management (Repeated)

2 The Treatment Revolution Dr Dianne Sharp Retina Specialists, Auckland

3 When straight lines become crooked Dr Dianne Sharp Retina Specialists, Auckland

4 Reduced vision: Measure visual acuity with distance glasses

5 Refractive errors

6 Refractive errors

10 Reduced vision improved with pinhole

11 Physiologic loss of accommodation in advancing age

12 Distortion: straight lines are crooked

13 Amsler grid

14 Straight lines crooked. Because of swelling: Under the retina In the retina On the retina

15 The macula = centre of retina retina optic nerve macula

16 Normal macula

17 Swelling UNDER the Retina: Wet Macular Degeneration

18 Swelling IN the Retina Diabetic Macular Oedema DME

19 Scrunching ON the Retina Epiretinal membrane ERM

20 Macular Degeneration 0800 MACULA ( )

21 Swelling UNDER the Retina: Wet Macular Degeneration

22 Macular degeneration Progressive central vision loss Peripheral vision remains Not total blindness

23 Chronic diseases: 3 x dementia, half diabetes Eyes on the future A clear outlook on age-related macular degeneration. Deloitte Access Economics and Macular Disease Foundation 2011.

$Uncorrected refractive error$ 4% Cataract 11% Other 21%

24 Leading cause of vision loss Uncorrected refractive error 4% Cataract 11% Other 21% Glaucoma 16% Macular degeneration 48%

25 In NZ Macular Degeneration affects: 1. 1 in 50 people over 50 years 2. 1 in 25 people over 50 years 3. 1 in 7 people over 50 years

26 1 in 7 over 50 years

27 1 in 4 over 80 years

28 2 x falls 3 x depression 8 x hip fracture 3 years earlier rest home

29 Difficulty with daily activities Fear of blindness Poor life satisfaction Impact on family Mitchell J, Bradley C. Quality of life in age-related macular degeneration: a review of the literature. Health Qual Life Outcomes 2006;4:97

30 4 x risk 10 years earlier

31 50% chance if family history tell your family

32 The macula retina optic nerve macula

33 Healthy retina retina RPE choroid

34 Early changes drusen Bruch s membrane thickens

35 Wet MD new vessels

36 Wet MD bleeding fluid leak

37 Amsler grid

38 Dry Wet slow and gradual sudden and severe

39 Dry MD Thinning or atrophy Drusen

40 Wet MD Haemorrhage and fluid leak under retina

41 75% blind with wet MD after 3 years no treatment 50% at 3 months Wong TY, Chakravarthy U, Klein R et al. The natural history of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology 2008;115:

Vascular Endothelial Growth Factor VEGF-A: 1 Normal role: growth of tissues and organs Pathological role neovascularisation and oedema Structure of the VEGF-A protein

42 Vascular Endothelial Growth Factor VEGF-A: 1 Normal role: growth of tissues and organs Pathological role neovascularisation and oedema Structure of the VEGF-A protein Illustration used with permission from the European Bioinformatics Institute. 1. Rudge JS et al. In: Angiogenesis: An Integrative Approach From Science to Medicine. 2008;

43 Treatment of Wet MD Anti-VEGF agents: Avastin/ Lucentis/ Eylea Block VEGF-A Stabilise vision and prevent further loss leaking blood vessel

44 Visual acuity 6/24 fluid 6/9 4 weeks after Eylea drusen

45 Moment of boredom! MR L age 67yr Positive family history for AMD RE LE

46 RE: 6/5 LE: 6/24

47 Fluorescein angiogram identifies abnormal blood vessels

48 Before treatment. Vision 6/24 After 3 months treatment. Vision 6/6

95% stable vision 40% driving vision 30% gain 3 lines vision 1. Bloch SB, Larsen M, Munch IC. Incidence of legal blindness from age-related macular degeneration in Denmark: year 2000 to 2010.

49 95% stable vision 40% driving vision 30% gain 3 lines vision 1. Bloch SB, Larsen M, Munch IC. Incidence of legal blindness from age-related macular degeneration in Denmark: year 2000 to Am J Ophthalmol 2012;153: Skaat A, Chetrit A, Belkin M et al. Time trends in the incidence and causes of blindness in Israel. Am J Ophthalmol 2012;153: Cackett P et al. Intravitreal ranibizumab treatment of wet macular degeneration in SE Scotland effect on blindness rates and 5 year follow up data. Presented at ARVO, 5 May 2013, Seattle WA, USA.

50 Less blindness in NZ 2005: Introduction of anti-vegf treatments

50% less in Denmark 1 51% less in Israel 2 59% less in

Incidence of legal blindness from age-related macular

Am J Ophthalmol 2012;153:209-213. 2. Skaat A, Chetrit A, Belkin M et al.

Israel. Am J Ophthalmol 2012;153:214-221. 3.

Intravitreal ranibizumab treatment of wet macular

51 50% less in Denmark 1 51% less in Israel 2 59% less in Scotland 3 1. Bloch SB, Larsen M, Munch IC. Incidence of legal blindness from age-related macular degeneration in Denmark: year 2000 to Am J Ophthalmol 2012;153: Skaat A, Chetrit A, Belkin M et al. Time trends in the incidence and causes of blindness in Israel. Am J Ophthalmol 2012;153: Cackett P et al. Intravitreal ranibizumab treatment of wet macular degeneration in SE Scotland effect on blindness rates and 5 year follow up data. Presented at ARVO, 5 May 2013, Seattle WA, USA.

53 2 to 3 times a week salmon, tuna, anchovies, sardines

54 Age Related Eye Disease Studies National Eye Institute, USA

55 AREDS 1 25% risk reduction of developing advanced MD 19% reduced risk vision loss in moderate to advanced MD

56 AREDS 1 and 2 Vitamin C 500 mg Vitamin E 400 IU Zinc 80 mg Copper 2 mg Lutein 10 mg Zeaxanthin 2 mg

57 Recommendations AREDS supplement for moderate and advanced MD Lutein if > 50, positive family history and insufficient green leafy vegetables

59 Awareness is the key 72% have ever heard of MD 59% know it affects the eye Galaxy Poll, 2016.

60 AWARENESS IS THE KEY New Zealand Australia 65% 76% 88% 88% 45% 41% 48% 59% MDNZ Galaxy poll March 2016

61 Blindness is no longer the inevitable consequence of Macular Degeneration 0800 MACULA ( )

62 Diabetic Macular Oedema

63 Swelling IN the Retina Diabetic Macular Oedema DME

64 Normal Vision Vision with DME

65 Major sites of Diabetic Complications

66 Which complication diabetic patients most concerned about? 1. Brain 2. Eyes 3. Heart 4. Kidney 5. Circulation

67 Complications patients most concerned about: Vision 50% 21% 11% 10% 9% 7% Vision / loss of sight Cardiac Renal Circulation Feet / legs Other Strain D et al. Diabetes Res Clin Pract 2014;.

68 Intensive therapy for IDDM over 6 yrs reduces risk of development of retinopathy by: 1. 95% 2. 76% 3. 54% 4. 36%

69 Effect of intensive therapy for type 1 DM 1 prevention: No DR 2 intervention: Mild BDR risk developing DR by 76 % compared with conventional therapy slowed progression of retinopathy by 54% development to severe NPDR or PDR by 47% N Engl J Med 1993 Sep 30;329(14):

Progression of diabetic retinopathy: Secondary intervention The

70 Diabetic Retinopathy: Intensive therapy delays onset & slows progression Onset of diabetic retinopathy: Primary prevention Progression of diabetic retinopathy: Secondary intervention The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993; 329:

71 Sustained control type 2 diabetics for 20yr Intensive therapy: median HbA 1c 53 mmol/ml (7.0%) Conventional: median HbA 1c 63 mmol/mol (7.9%) RESULT: Microvascular complication rate by 25%. Every 11mmol/mol decr in HbA lc eg.75 to 63 (9 to 8%) risk of complications by 35%

72 Early & sustained glycaemic control is important 20- and 30-year follow-up results UKPDS original results: Intensive vs. conventional treatment 10-year post-trial follow-up (non-interventional) Randomisation 1997 (20 years) 2007 (30 years) 12% * 9% * 9% * Any diabetes-related endpoint 16% 15% * Microvascular disease Myocardial infarction 25% * In type 2 diabetes, improved glycaemic 24% * control reduces the risk P<0.05; intensive vs. conventional treatment. of complications UKPDS, United Kingdom Prospective Diabetes Study. Holman RR et al. N Engl J Med 2008; 359: UKPDS 33 Study Group. Lancet 1998; 352:

73 Diabetic Retinopathy Disease Severity Score No apparent DR Mild NPDR Moderate NPDR Severe NPDR Proliferative DR (PDR) Macular Oedema can develop at any stage of DR (or may not occur)

74 Diabetic Macular Oedema

75 Normal Retina

76 Early Diabetic Macular Oedema (DME)

77 Clinically significant DME High levels of VEGF increases vascular permeability

78 Treatment of Diabetic macular oedema Anti-VEGF agents: Avastin, Lucentis and Eylea block VEGF-A leaking blood vessel

BCVA (ETDRS letters) Initial rapid gains in visual acuity are *. 14 12 10 8 6 4 2 0 maintained over 100 weeks VIVID week 100 10.7 2q8 * 10.5 2q4 * 1.

2 Laser 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 Korobelnik J-F et al. Ophthalmology 2014; Epub ahead of print. 100 11.5 2q4 * 11.1 2q8 * 0.

80 BCVA (ETDRS letters) Initial rapid gains in visual acuity are * maintained over 100 weeks VIVID week q8 * q4 * 1.2 Laser q4 * 9.4 2q8 * 0.7 Laser VISTA week q4 * q8 * 0.2 Laser Korobelnik J-F et al. Ophthalmology 2014; Epub ahead of print q4 * q8 * 0.9 Laser Week Laser 2q4 2q8 * P< vs. laser. VIVID: Laser: n=132; 2q4: n=136; 2q8: n=135; VISTA: Laser: n=154; 2q4: n=154; 2q8: n=151 Full analysis set. 2q4, 2 mg every 4 weeks; 2q8, 2 mg every 8 weeks; BCVA, best corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study

81 Anti VEGF Treatment DME AntiVEGF superior to focal laser Delaying treatment reduces response

84 AntiVEGF Treatment DME Early recognition is important Delaying treatment reduces response Delay 1 year may respond with time but require more treatments Delay 2 years may be unresponsive

85 Diabetic Macular Oedema is major cause of vision loss in Diabetes Delaying treatment may delay response

86 Scrunching ON the Retina Epiretinal membrane ERM

87 RE Mild Vitreomacular traction LE

88 Mr K Mild Epiretinal membrane 2013 RE VA 6/ RE VA 6/7.5

89 Severe vitreomacular traction threatening vision

90 Severe Epiretinal Membrane

91 Severe Epiretinal Membrane

92 Severe ERM: Surgery

93 Distortion may require urgent treatment 0800 MACULA ( )

Good News for The Macular Generation. Dr Andrew Thompson FRANZCO

Good News for The Macular Generation Dr Andrew Thompson FRANZCO Anti-VEGFs for wet MD are one of the greatest advances in medicine in past decade Prof. Gary Brown Director Wills Eye Institue Retina Service