update on diabe-c re-nopathy varma r et al. prevalence of diabetic retinopathy in adult latinos;...

UpdateonDiabe-cRe-nopathy www.re-nasarasota.com

1

Update on Current Definitions and Treatment of Diabetic

Retinopathy

Beth Richter, MD, PhD Retina Associates of Sarasota

January 2017

No financial disclosures.

I will be discussing off label use of bevicizumab.

Plan !  Case discussions

!  Background/prevalence/diabetic goals

!  Pathophysiology of Diabetic Retinopathy

!  Overview of diabetic retinopathy definitions

!  Treatment options

!  Clinical trials

!  Future directions

Case 1 Type 2 NIDDM x 15 years

20/20 Vision OS


2

Case 2 Type 2 NIDDM x 15 years

20/50 Vision


3

Case 3 Type 2 IDDM x 20 years

20/200 Vision OD

Diabetic Retinopathy !  Leading cause of new legal blindness among working

age individuals in the US (20-64 year olds)

!  US Prevalence rate 40+ year olds: 28.5% (4.2 million)

!  Worldwide prevalence 34.6% (93 million people)

Klein, BE. Overview of epidemiologic studies of diabetic retinopathy among US adults. Ophthalmic Epidemiology 2007; 14: 179-83.

Vision Threatening Diabetic Retinopathy

!  United States 4.4% (0.7 million)

!  Worldwide 10.2% (28 million)

!  2020 projection in US: !  6 million with retinopathy !  1.34 million with vision threatening diabetic

retinopathy


4

Duration of diabetes is most important

Type 1

!  5 years 25% with retinopathy




!  PDR present in 50% for those with 20+ years of diabetes (in those patients less than 30 years old)

Klein R. et al. The Wisconsin Epidemiological Study of Diabetic Retinopathy. Arch Ophthalmol. 1984; 102: 520-6. Varma R et al. Prevalence of Diabetic Retinopathy in Adult Latinos; Ophthalmol 2004; 121: 1298-306.

Duration of diabetes is most important

Type 2

!  30+ year olds with DM2 less than 5 years !  40% using insulin have diabetic retinopathy !  24% not requiring insulin have diabetic retinopathy

!  19 years duration !  60% have diabetic retinopathy

!  Approximately 84% using insulin !  53% in non-insulin users

!  Proliferative Diabetic Retinopathy !  <5 years, 2% have PDR !  25 years, 25% have PDR

American Diabetes Association Retinopathy Screening 2015 !  Performed by optometrist of ophthalmologist

within 5 years of diagnosis for Type 1 DM (>10yo)

!  Shortly after diagnosis of Type 2 DM

!  Annual examinations, unless retinopathy is progressing

!  Women with diabetes who are contemplating pregnancy and also follow-ups during pregnancy


5

U.S. Age-Adjusted Percentage of Adults with Diagnosed Diabetes Receiving a Dilated Eye Exam

in the Last Year

50

55

60

65

70

1994 1998 2002 2006 2010

Percent

CDC.Gov Preventative Statistics 1994-2010 https://www.cdc.gov/diabetes/statistics/preventive/fx_eye.htm

0

10

20

30

40

50

60

70

80

90

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

75+

65-74

45-64

18-44

U.S. Percentage of Adults with Diagnosed Diabetes Receiving a Dilated Eye Exam in the Last

Year

Diabetic Primary care screening

!  Glycemic control

!  BP evaluation

!  Cholesterol evaluation

!  Urinary albumin excretion

!  Renal function

!  Medication adherence

!  Foot examination

!  Retinal examination

!  Dental examination


6

Primary Diabetic Goals !  Emphasize importance of Diabetes Self

Management Education (DSME)

!  Education about glycemic control and microvascular risk

!  Discussion of asymptomatic nature of diabetic eye disease

!  Overcome barriers !  Cost and insurance coverage of eye care !  “But I don’t need new glasses”

Glucose Control !  UKPDS- United Kingdom Prospective Diabetes Study

!  Type 2 Diabetes

!  4209 patients from 1977-1999 !  25-65 year olds

!  Conventional versus intensive therapy !  1 point drop in HgbA1c= reduced progression by 35% !  47% reduction in moderate vision loss

Holman et al. NEJM 359; 2008: 1577-1589

Glucose Control !  DCCT- Diabetes Control and Complications Trial

!  Type 1 Diabetes

!  1441 patients from 1983-1993 !  Conventional versus intensive therapy

Patients with 3 steps of DR change from baseline

NEJM 1993; 329: 977-986

Primary prevention (no DR) Secondary prevention (mild to mod NPDR)


7

HgbA1C and Glycemic Control

!  Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and multiple randomized trials has shown increased risk of mortality with HgbA1C <6.5

!  Recent studies including an older population with diabetes have shown a U- shaped relationship of increased mortality associated with low HbA1c.

Abdelhafiz A.H., et al. Low Hba1C and Increased Morality Risk-Frailty a Confounding Factor? Aging Disease. 2015 Aug; 6(4): 262-270

Frailty and HgbA1c !  No direct causal link between low HbA1c and

mortality

!  Unclear mechanism of A1c and mortality relationship

!  Importantly in these studies- functional status, disability, or frailty was not routinely measured

!  Perhaps malnutrition, inflammation, and functional decline are characteristics shared by the populations that showed increased mortality and low HbA1c

Abdelhafiz A.H., et al. Low HbA1c and Increased Mortality Risk-Is Frailty a Confounding Factor? Aging Disease. 2015 Aug; 6(4): 262-270


8

Pathophysiology of DR

Remya Robinson et al. Dis. Model. Mech. 2012;5:444-456

© 2012. Published by The Company of Biologists Ltd

Other Aspects to Consider !  Endocrine Control

!  HgbA1c

!  Blood Pressure

!  Hyperlipidemia

!  Kidney Problems

!  Neuropathy

!  Aspirin is NOT shown to change diabetic retinopathy or complications of vitreous hemorrhage

ETDRS Research Group. Effects of aspirin treatment on diabetic retinopathy:ETDRS report number 8. Ophthalmology 1991;98:757-65. Chew EY et al. Effects of aspirin on vitreous/preretinal hemorrhage in patients with diabetes mellitus: ETDRS report number 20. Arch Ophthalmol 1995;113:52-5.


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Defining Diabetic Retinopathy !  Macula Evaluation

!  Peripheral Evaluation

!  Supplementary Testing: !  OCT !  Fluorescein Angiography

Based on American Academy of Ophthalmology Retina/Vitreous Panel. Preferred Practice Pattern® Guidelines. Diabetic Retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2016. Available at: www.aao.org/ppp.

Diabetic Macular Edema

Diabetic Macular Edema !  Affects 10% of all diabetic patients1

!  Moderate vision loss

!  Causes decreased vision, contrast sensitivity, metamorphopsia

!  If patients notice the symptoms- easier to talk about need for therapy

!  Exudates, microaneurysms, leakage on fluorescein angiography, OCT thickening

!  Can have uninvolved fovea 1 Chen E, et al. Burden of illness of diabetic macular edema: literature review. Curr Med Res Opin. 2010;26:1587-1597.


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OCT

Clinically Significant Macular Edema (CSME)

Defined by the ETDRS to include any of the following features:

!  Thickening of the retina at or within 500 µm of the center of the macula

!  Hard exudates at or within 500 µm of the center of the macula, when associated with adjacent retinal thickening.

!  A zone or zones of retinal thickening one disc area or larger, where any portion of the thickening is within one disc diameter of the center of the macula

Newest terminology !  ci-CSME Center-Involving Clinically Significant Macular Edema !  nci-CSME Non-Center-Involving CSME (diffuse or elsewhere)


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Peripheral Examination

!  Mild Nonproliferative

!  Moderate

!  Severe

!  Very Severe

!  Proliferative

Severe NPDR is defined by the ETDRS study and 4:2:1 rule «  4 quadrants with diffuse intraretinal hemorrhages and

microaneurysms

«  2 quadrants with venous beading

«  1 quadrant with intraretinal microvascular abnormalities

Stages of Diabetic Retinopathy

è Microaneurysms only

★

★★ èNeovascularization or vitreous hemorrhage present

Progression to PDR

50%

75% in 1 year

ETDRS Research Group. Early photocoagulation for diabetic retinopathy: ETDRS report number 9. Ophthalmology 1991;98:766-85.

High-Risk PDR

15%

45% in 1 year


12

“Diabetes2000:EliminationofPreventableBlindnessfromDiabetesby

theYear2000”Ophthalmology1991;98:739-40.

October17,2016 Diabetes2016:CourseonDiabeticRetinopathy

Proliferative Diabetic Retinopathy

!  Can cause severe vision loss

!  Complications !  Traction Retinal Detachments !  Vitreous Hemorrhage !  Neovascular Glaucoma

!  “High-Risk PDR”= any 3 of these !  NVD !  NVE !  Vitreous Hemorrhage/preretinal heme !  Severe NV ( ¼ - 1/3 NVD or ½ Disc Area NV)


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Traction Retinal Detachment

Treatments Available !  Laser

!  Focal Macular Laser !  PRP

!  Injections !  Anti-VEGF

!  Bevicizumab !  Ranimizumab !  Aflibercept

!  Steroid !  Dexamethasone !  Fluocinolide !  Triamcinolone

!  Surgery !  Removal of Hyaloid Face

!  Vitreomacular Traction !  Traction Retinal Detachments

PRP


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TABLE 6 MANAGEMENT RECOMMENDATIONS FOR PATIENTS WITH DIABETES Severity of Retinopathy Presence of

Macular Edema Follow-up (Months)

Panretinal Photocoagulation

(Scatter) Laser

Focal and/or Grid Laser*

Intravitreal Anti-VEGF Therapy

Normal or minimal NPDR No 12 No No No Mild NPDR No

ME CSME†

12 4–6 1*

No No No

No No

Sometimes

No No

Sometimes

Moderate NPDR No ME

CSME†

12‡ 3–6 1*

No No No

No No

Sometimes

No No

Sometimes

Severe NPDR No ME

CSME†

4 2–4 1*

Sometimes Sometimes Sometimes

No No

Sometimes

No No

Sometimes

Non-high-risk PDR No ME

CSME†

4 2-4 1*

Sometimes Sometimes Sometimes

No No

Sometimes

No No

Sometimes

High-risk PDR No ME

CSME†

4 4 1*

Recommended Recommended Recommended

No Sometimes Sometimes

Alternative129,130 Usually Usually

Anti-VEGF = anti-vascular endothelial growth factor; CSME = clinically significant macular edema; ME = non-clinically significant macular edema; NPDR = nonproliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy * Adjunctive treatments that may be considered include intravitreal corticosteroids or anti-VEGF agents (off-label use, except aflibercept and

ranibizumab). Data from the Diabetic Retinopathy Clinical Research Network in 2011 demonstrated that, at two years of follow-up, intravitreal ranibizumab with prompt or deferred laser resulted in greater visual acuity gain and intravitreal triamcinolone acetonide plus laser also resulted in greater visual gain in pseudophakic eyes compared with laser alone.131 Individuals receiving the intravitreal injections of anti-VEGF agents may be re-examined as early as one month following injection.

† Exceptions include hypertension or fluid retention associated with heart failure, renal failure, pregnancy, or any other causes that may aggravate macular edema. Deferral of photocoagulation for a brief period of medical treatment may be considered in these cases.132 Also, deferral of CSME treatment is an option when the center of the macula is not involved, visual acuity is excellent, close follow-up is possible, and the patient understands the risks.

‡ Or at shorter intervals if signs approaching those of severe NPDR appear.

Follow Up Recommendations

American Academy of Ophthalmology Retina/Vitreous Panel. Preferred Practice Pattern® Guidelines. Diabetic Retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2016. Available at: www.aao.org/ppp.

1985 1976-81 2008 2010 2012 2014 2005

Macular Laser Photocoagulation

VEGF Inhibitors

ETDRS2 Bevacizumab BOLT Study6

Ranibizumab RISE/RIDE

Studies7

FDA Approval

Intravitreal Aflibercept Injection

VISTA/VIVID Studies8,11

FDA Approval

Triamcinolone Acetonide DRCRnet

Protocol B3

Fluocinolone Acetonide

FAME Study4

Dexamethasone MEAD Study5

FDA Approval

Intravitreal Steroids

1.  Preliminary report on effects of photocoagulation therapy. The DRS Research Group. Am J Ophthalmol. 1976 Apr;81(4):383-96.

2.  ETDRS Research Group. Arch Ophthalmol. 1985;103(12):1796-1806.

3.  Diabetic Retinopathy Clinical Research Network. Ophthalmology. 2008;115(9):1447-1459.

4.  Campochiaro PA et al. Ophthalmology. 2010;117(7):1393-1399. 5.  Boyer DS, Yoon YH, Belfort R, et al. Ozurdex MEAD Study Group.

Ophthalmology. 2014 6.  Michaelides M et al. Ophthalmology. 2010;117(6):1078-1086 7.  Nguyen QD et al. Ophthalmology. 2012;119(4):789-801. 8.  Korobelnik JF et al. Ophthalmology 2014 9.  DRCR net Writing Committee; Haller JA, Qin H, Apte RS, et al.

Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology. 2010;117:1087-1093.

Pars Plana Vitrectomy

DRCRnet Protocol D9,10

2016

DRTreatmentLandmarks

DRS1

Protocol S12

Protocol T13,14

10.  Flaxel CJ, Edwards AR, Aiello LP, et al. Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: DRCR network. Retina. 2010;30:1488-1495.

11.  Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies. Ophthalmology. 2015 Oct;122(10):2044-52.

12.  Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Trial. JAMA. 2015; 314(20):2137-2146.

13.  Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203.

14.  Wells JA et all. Aflibercept, Bevacizumab, or Ranibizumab for DME Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial Ophthalmology 2016;123:1351- 1359.

TABLE A4-1 VISUAL OUTCOME FOR LASER PHOTOCOAGULATION FROM THE DIABETIC RETINOPATHY STUDY Baseline Severity of Retinopathy Duration of Follow-up

(Years) Control Patients

(% with Severe Visual Loss) Treated Patients

(% with Severe Visual Loss)

Severe nonproliferative 2 4

3 13

3 4

Mild proliferative 2 4

7 21

3 7

High-risk proliferative 2 4

26 44

11 20

NOTE: Severe visual loss was defined as worse than 5/200 visual acuity at two or more consecutive completed visits (scheduled at 4-month intervals).

Diabetic Retinopathy Study !  Established value of laser photocoagulation surgery

for patients with severe NPDR and PDR


15

!  3 line vision gain *gold standard to be compared to*

!  3711 patients, completed in 1985

!  50% reduction in 3 line vision loss

!  15% of patients improved by 3 lines TABLE A4-2 VISUAL OUTCOME FOR LASER PHOTOCOAGULATION TREATMENT FROM THE EARLY TREATMENT DIABETIC

RETINOPATHY STUDY Extent of Macular Edema Duration of Follow-up

(Years) Control Patients

(% with Visual Loss) Treated Patients

(% with Visual Loss)

CSME (center of macula not involved)

1 2 3

8 16 22

1 6

13

CSME (center of macula involved)

1 2 3

13 24 33

8 9

14

CSME = clinically significant macular edema NOTE: Visual loss was defined as at least doubling of the visual angle.

ETDRS- focal laser

1985 1976-81 2008 2010 2012 2014 2005


VEGF Inhibitors



Studies7

FDA Approval



FDA Approval


Protocol B3


FAME Study4


FDA Approval










2016


DRS1

Protocol S12

Protocol T13,14






DRCR.net Protocol D- Vitrectomy !  87 eyes

!  Eyes with DME and vitreomacular traction

Macular Thickness Decreased Visual Outcome Mixed

28-49% of eyes with improvement of visual acuity 13-31% had worsening of visual acuity


16

1985 1976-81 2008 2010 2012 2014 2005


VEGF Inhibitors



Studies7

FDA Approval



FDA Approval


Protocol B3


FAME Study4


FDA Approval










2016


DRS1

Protocol S12

Protocol T13,14






DRCR.net Protocol B !  840 eyes with DME

!  Focal/grid laser !  1mg triamcinolone !  4mg triamcinolone

!  At 4 months, 4mg triamcinolone had better VA

!  At 1 year, no significant differences

!  At 3 years, visual acuity better in laser group

!  Problems with steroids !  Elevation of IOP !  Need for cataract surgery

Steroids- MEAD study !  Sustained-release Dexamethasone implant study

!  DEX implant 0.7mg (n=351) 22% 3-line improvement

!  DEX 0.35mg (n=347) 18% improvement

!  Sham injection (n=350) 12% improvement

!  Average 4 injections (every 6 months), 3 year follow up

!  Cataract formation deteriorated vision


17

Comparison of DEX Implant in Total MEAD Population

Improvement in BCVA provided by DEX implant reduced by month 15; trend to improve by year 3 after cataract surgery

1. Boyer et al. Ophthalmology.2014; 121(10):1904-1914..

Mea

n C

hang

e Fr

om B

asel

ine

(Let

ters

)

DEX implant 0.7 mg (n = 351) DEX implant 0.35 mg (n = 347) Sham (n = 350)

Month *P ≤ .046 vs sham.

Comparison of DEX Implant in Pseudophakic Eyes

BCVA improvement in pseudophakic eyes treated with DEX implant was consistently significantly better than sham over the 3-year study with no loss of treatment benefit

1. Boyer et al. Ophthalmology.2014; 121(10):1904-1914..

Mea

n C

hang

e Fr

om B

asel

ine

(Let

ters

)

DEX Implant 0.7 mg (n = 86) DEX Implant 0.35 mg (n = 88) Sham (n = 101)

Month *P ≤ .046 vs sham.

Injection of Dexamethasone !  23 Ga needle at bevel

!  Teflon coating of insertion device

!  Clinical insertion under topical anesthetic

Allergan video of device


18

0.2 µg/d Fluocinolone Acetonide (FAc) Intravitreal Implant (ILUVIEN®)

•  Indicated for the treatment of

diabetic macular edema in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure

•  Implant is a cylindrical tube, 3.5 mm long × 0.37 mm diameter ≈ 0.38 µL

•  Inserted into the eye through a self-sealing wound via a 25-gauge needle in a specially designed applicator

•  Nonbioerodible polyimide shell

•  Releases a submicrogram daily dose of the steroid FAc

ILUVIEN Prescribing Information.

0

5

10

15

20

25

30

35

40

0 3 6 9 12 15 18 21 24 27 30 33 36

Control (n = 185) 0.2 µg/d FAc (ILUVIEN;

Months

Patie

nts

With

≥ 1

5-Le

tter I

mpr

ovem

ent

in B

CVA

Fro

m B

asel

ine,

%

FAME Study Efficacy: Percentage of Patients With ≥ 15-Letter Improvement

Primary readout

28.7%

16.2%

P = .002

Campochiaro PA, et al. Ophthalmol. 2011;118:626-635; Campochiaro PA, et al. Ophthalmol. 2012;119:2125-2132. ILUVIEN Prescribing Information.

Study Outcomes 0.2 µg/d FAc (ILUVIEN) Sham Estimated

Difference

FAME A Gain of ≥ 15 letters in BCVA, n (%) 51 (27) 14 (15)

12.1 (2.6 to 21.6)

FAME B Gain of ≥ 15 letters in BCVA, n (%) 57 (31) 16 (18)

13.0 (2.7 to 23.4)

1985 1976-81 2008 2010 2012 2014 2005


VEGF Inhibitors



Studies7

FDA Approval



FDA Approval


Protocol B3


FAME Study4


FDA Approval










2016


DRS1

Protocol S12

Protocol T13,14







19

Bevicizumab or Laser Therapy (BOLT)

!  Patients with persistent DME and visual impairment

!  2 year outcome !  Intravitreal 1.25 mg bevacizumab injections (every 6 weeks) !  Focal laser treatment (every 4 months).

!  Bevicizumab patients 5.1 times as likely to gain at least 10 letters

!  No patients lost 10 or more letters in the bevacizumab group, compared with 14% of patients treated with laser.

Bevicizumab

Focal Laser

RISE/RIDE Time to first progression to PDR

VISTA/VIVID !  Center-involving DME

!  Aflibercept 2mg every 4 weeks

!  Aflibercept 2mg every 8 weeks after 5 monthly doses

!  Laser

!  Primary endpoint was 52 weeks

!  Now results up to 3 years have been published- similar to year 1 and year 2 n Aflibercept 2mg Q8weeks

Δ Aflibercept 2mg Q4weeks ¢ Control group

Heier et al. Ophthalmology. 2016 Nov;123(11):2376-2385.


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DRCR Protocol T !  Compared results of different anti-VEGF injections

!  Bevacizumab

!  Ranimizumab !  Aflibercept

!  Overall, there was not a statistically significant difference between 3 different drugs

0

2

4

6

8

10

12

14

16

18

20

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

Mea

n C

hang

e in

Vis

ual

Acu

ity

Lett

er S

core

Weeks

Aflibercept Bevacizumab Ranibizumab

Protocol T- comparing 3 anti-VEGF agents Mean Change in Visual Acuity Over 2 Years

+13.3

+11.2

+9.7 +10.0

+12.3

+12.8

0 8 16 24 32 40 48 56 64 72 80 88 96 104

20/50 or Worse

0

2

4

6

8

10

12

14

16

18

20

0 8 16 24 32 40 48 56 64 72 80 88 96 104

Mea

n C

hang

e in

Vis

ual

Acu

ity

Lett

er S

core

Weeks

20/32 to 20/40

+13.3

+16.1 +18.1

+8.6 +7.8

+6.8

DRCR.net Protocol T Mean Change in Visual Acuity Over 2 Years

By Baseline Visual Acuity Subgroup


21

DRCR.net Protocol S- anti-VEGF vs. PRP for PDR

!  Study question: Is ranimizumab non-inferior to PRP for treatment of PDR?

!  2 year data published

DRCR.net Protocol S Mean Change in Visual Acuity

Outlying values were truncated to 3 SD from the mean

-5

0

5

10

15

0 16 32 52 68 84 104

Mea

n Vis

ual

Acu

ity

Cha

nge

(Let

ter

Sco

re)

Visit Week

Ranibizumab Group PRP Group

N = 191 N = 203

+ 2.8

+ 0.2

N = 168 N = 160

2-Year Adjusted Mean Difference: +2.2 letters 95% Confidence Interval: (-0.5, +5.0) (Meets pre-specified non-inferiority criterion: lower bounds of the 95% CI of -0.5 letters was greater than the non-inferiority limit of -5.0 letters)

1985 1976-81 2008 2010 2012 2014 2005


VEGF Inhibitors



Studies7

FDA Approval



FDA Approval


Protocol B3


FAME Study4


FDA Approval










2016


DRS1

Protocol S12

Protocol T13,14







22

VEGF or inflammation driven? !  Inflammatory cytokines are elevated in the eyes of

patients with diabetes1

!  Inflammatory cytokines are expressed at a higher level in eyes with DME2

!  Theory that diabetic eye disease changes at some point from primarily anti-VEGF-driven to primarily inflammation-driven

1 Dong N et al. Study of 27 aqueous humor cytokines in patients with type 2 diabetes with or without retinopathy. Mol Vis. 2013;19:1734-1746. 2 Funatsu H, et al. Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology. 2009;116:73-79.

DRCR Protocol I !  Comparison of

!  Laser alone

!  Ranimizumab + prompt laser !  Ranimizumab + deferred laser

!  Triamcinolone + prompt laser

Pseudophakic eyes

EARLY analysis of Protocol I data (anti-VEGF only)

!  Post-hoc assessment of only the ranimizumab-treated eyes in Protocol I

!  After 3 injections, can predict the response that will be achieved with anti-VEGF

!  Split these into 3 groups based on improvement !  <5 letters !  5-9 letters !  10+ letters

!  Patients stayed in the same groups at 3 year followup Gonzalez VH et al. Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol I data. Am J Ophthalmol. Sep 2016 ; 172: 72-79.


23

Future directions !  DRCR.net Protocol V explores using anti-VEGF on

asymptomatic very good vision patients !  Observe

!  Anti-VEGF !  Laser

!  DRCR.net Protocol AB compares anti-VEGF to surgical treatment of vitreous hemorrhage from PDR

OCT Angiography


24

Friberg and Karatza. Ophthalmology 1997; 104:2030-2038

67% duty cycle

Micropulse Regimens are Nonstandardized Study Waveleng

th(nm)NumberofSpots

SpotSizeμ

Power FAZ DutyCycle%

DuraIon(ms)

Lavinsky(citedinBlumenkranz)

532 768,.25burnspacingbetweenburns

200 120%ofthepoweryieldingafaintburnincon-nuouswavemode(30%ofenergyrequiredforthresholdburnincwmode)

Treat 15 300

Nicolo 577 250-450 200 200mW Treat 5 200

Figueira 810 Confluent 125 200%ofthepoweryieldingafaintburnincon-nuouswavemode

Treat 15 300

Lavinsky 810 Gridwithspots2spotdiametersapart

125 120%ofthepoweryieldingafaintburnincon-nuouswavemode

Treat 15 300

Lavinsky 810 Confluent 125 120%ofthepoweryieldingafaintburnincon-nuouswavemode

Treat 15 300

LuWrull 810 Confluent 125 780-930mW Treat 5-15 100-300

Vujosevic 810 Notgiven 125 750mW Spare 5 200

Othman 810 100-750 75-125

1,000mW Spare 15 300

Takatsuna 810 Notgiven

200 200%ofthepoweryieldingafaintburnincon-nuouswavemode(460-960mw)

Treat 15 100

Friberg 810 Grid,#notgiven

75-200

150-1200 Treat 67 200-400

Outcomes Study N

(eyes)MeanBLBCVA

Mean12MoChangeinBCVA(leTers)

MeanBLCSMT

12MoChangeinMeanCSMT,µ

Figueira 84 20/28 -3 249 +42

Othman 220 20/32 +1.5 353 -138

Takatsuna 56 20/59 +3.5 504 -184

Ohkoshi 43 20/26 0 342 -47

Vujosevic 32 20/32 -1.5 358 -46

Lavinsky(NDMP)

42 20/100 -5 379 -68

Lavinsky(HDMP)

39 20/158 +19 371 -145

Decreases thickness. True effect on vision?


25

!  “Physicians should prescribe metformin to patients with type 2 diabetes when medication is needed to improve high blood sugar, the American College of Physicians (ACP) recommends in an evidence-based clinical practice guideline published today in Annals of Internal Medicine.

!  If a second oral medication is needed to improve high blood sugar, ACP recommends that physicians consider adding either a sulfonylurea, thiazolidinedione, SGLT-2 inhibitor, or DPP-4 inhibitor to metformin.”

DRCR.net Protocol AB !  Patient recruitment:

!  Type 1 or 2 diabetes !  Vitreous hemorrhage causing visual impairment

(any vision level 20/32 to LP) !  Lens status does not matter !  Prior PRP does not matter

!  No eye surgery within 4 months or anti-VEGF for 2 months !  Cannot have a retinal detachment or TRD !  Cannot have prior vitrectomy history !  Cannot be on dialysis or have kidney transplant

!  Randomized to monthly aflibercept injections or immediate vitrectomy with PRP (within 2 weeks)

!  Primary outcome= 24 weeks, duration of study 2 years

More information on these slides: http://www.retinasarasota.com

Beth Richter, MD, PhD

Retina Associates of Sarasota Offices in Bradenton, Sarasota, Venice, and Port Charlotte

[email protected] Cell 777-0454

For 2 hours of transcript-quality CE, look for correspondence from NOVA

within the next 2 weeks Contact: Vanessa McDonald

Program Manager of Continuing Education 954-262-4224 Office [email protected] 954-262-1818 Fax

update on diabe-c re-nopathy varma r et al. prevalence of diabetic retinopathy in adult latinos;...

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