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Jay M. Haynie, OD, FAAO
Executive Clinical Director – Retina and Macula Specialists
Diabetic RetinopatathyFinancial Disclosure
I have received honoraria or am on the advisory board for the following companies:
Carl Zeiss Meditec Advanced Ocular
Arctic DX – Macula Risk Care
Genentech USA – USMA Lampa Advisory
Diabetic Retinopathy Diabetic Retinopathy
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.
Diabetic Retinopathy
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.
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Diabetic Retinopathy
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.
Diabetic Retinopathy
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.
Diabetic Retinopathy
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
Diabetic
Retinopathy
Leading cause
of blindness
in working age
adults
Diabetic
Neuropathy
Leading cause of non-traumatic
lower extremity amputations
Diabetic
Nephropathy
Leading cause of
end-stage renal disease
Stroke
Cardiovascular
Disease
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)
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
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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%
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 do the results of the Hemoglobin A1c
mean….?Diabetic Retinopathy
What is our role??
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Diabetic Retinopathy
- Classification of Diabetic Retinopathy:
Non Proliferative Diabetic Retinopathy
Mild
Moderate
Severe
Very Severe
Proliferative Diabetic Retinopathy
Diabetic Retinopathy
- Classification of Diabetic Retinopathy:
H/MA – hemorrhage or microaneurysm
VB – venous beading
IRMA – intraretinal microvascular abnormalities
NEO - neovascularization
Diabetic Retinopathy
- Classification of Diabetic Retinopathy:
Mild Non Proliferative Diabetic Retinopathy
At least one microaneurysm
Characteristics not met for more severe
retinopathy
Diabetic Retinopathy
OCT Angiography (OCTA)
Diabetic Retinopathy
- Classification of Diabetic Retinopathy:
Moderate Non Proliferative Diabetic Retinopathy
H/MA greater than standard photograph No. 2A and/or
Cotton wool spots, VB, or IRMA present
Characteristics not met for more severe retinopathy
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Diabetic Retinopathy
- Classification of Diabetic Retinopathy:
Severe Non Proliferative Diabetic Retinopathy
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
Diabetic Retinopathy
- Classification of Diabetic Retinopathy:
Very Severe Non Proliferative Diabetic Retinopathy
Two or more criteria of Severe NPDR
No frank neovascularization
Diabetic Retinopathy
- Classification of Diabetic Retinopathy:
H/MA’s in 4 quadrants = Severe Non PDR
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Diabetic Retinopathy
- Classification of Diabetic Retinopathy:
IRMA in 2 quadrants = Severe Non PDR
Diabetic Retinopathy
- Classification of Diabetic Retinopathy:
H/MA’s in 4 quadrants = Severe Non PDR
IRMA in 2 quadrants = Severe Non PDR
Diabetic Retinopathy
Rate of Progression to PDR
1 year 3 years
Mild NPDR 5 % 14%
Moderate NPDR 12-26 30-48
Severe NPDR 52 71
Diabetic Retinopathy
- Classification of Diabetic Retinopathy:
Proliferative Diabetic Retinopathy
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
Diabetic Retinopathy
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.
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Diabetic Retinopathy
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)
Diabetic Retinopathy
Treatment: Diabetic Macular Edema (antiVEGF)Comparative Effectiveness Study
of Intravitreal Aflibercept,
Bevacizumab, and Ranibizumab
for Diabetic Macular Edema
(Protocol T)
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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
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Protocol T
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.
Mean Change in Visual Acuity Letter Score
Baseline Visual Acuity 20/32 to 20/40
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
ME
AN
CH
AN
GE
IN
VIS
UA
L A
CU
ITY
LE
TT
ER
SC
OR
E
WEEKS
Aflibercept Bevacizumab Ranibizumab
~+ 8
~50% of Cohort
Mean Change in Visual Acuity Letter Score
Baseline Visual Acuity 20/50 or Worse
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
ME
AN
CH
AN
GE
IN
VIS
UA
L A
CU
ITY
LE
TT
ER
S
CO
RE
WEEKS
Aflibercept Bevacizumab Ranibizumab
* P-values adjusted for baseline visual acuity and multiple comparisons
+19
+14
+12
~ 50% of Cohort
Protocol T
Results:
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.
Mean Change in Visual Acuity Over 2 Years
Full Cohort
* P-values adjusted for baseline visual acuity and multiple comparisons
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
ME
AN
CH
AN
GE
IN
VIS
UA
L A
CU
ITY
LE
TT
ER
S
CO
RE
WEEKS
Aflibercept Bevacizumab Ranibizumab
+13.3
+11.2
+9.7 +10.0
+12.3
+12.8
Mean Change in Visual Acuity Over 2 Years
Baseline Visual Acuity 20/50 or Worse
* P-values adjusted for baseline visual acuity and multiple comparisons 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
ME
AN
CH
AN
GE
IN
VIS
UA
L A
CU
ITY
LE
TT
ER
SC
OR
E
WEEKS
Aflibercept Bevacizumab Ranibizumab
+18.9
+14.2
+11.8
+13.3
+16.1
+18.1~50% of
Cohort
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New description
CSME has now been further characterized
Center involved edema
Non center involved edema
Diabetic Macular Edema:
Center Involved Macular Edema
Diabetic Macular Edema:
Clinical Trials
Non - Center Involved Macular Edema
Diabetic Macular Edema:
Clinical Trials Diabetic Retinopathy
Treatment: Proliferative Diabetic Retinopathy
The Diabetic Retinopathy Study showed
that scatter laser PRP reduced the
incidence of severe vision loss by up to
50 % in patients with Proliferative
Diabetic Retinopathy.
Severe vision loss is < 5/200
Diabetic Retinopathy
Treatment: Proliferative Diabetic Retinopathy
Diabetic Retinopathy
Treatment: Proliferative Diabetic Retinopathy
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Diabetic Retinopathy
Treatment: Proliferative Diabetic Retinopathy
INSERT CLARUS IMAGE HERE OF PRP
Diabetic Retinopathy
Proliferative Diabetic Retinopathy - OCTA
AngioPlex VRI slice confirms neovascularization (NVE)
55 year old man with Type I Diabetes
AngioPlex / FA images showing neovascularization (NVE)
as well as the enlarged FAZ
55 year old man with Type I Diabetes
Diabetic Retinopathy
Proliferative Diabetic Retinopathy - OCTA
Diabetic Retinopathy
Even with treatment and resolution of macular
edema some patients continue to have severe vision
loss….. Driven by ischemia!
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Diabetic Retinopathy
OCT angiography – Zeiss AngioPlex
Diabetic Retinopathy
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.
Diabetic Retinopathy
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Vitreous Hemorrhage and Traction Retinal
Detachments
Diabetic Retinopathy Diabetic Retinopathy
Diabetic Retinopathy Diabetic Retinopathy
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
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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
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
Type I Diabetes with Proliferative Retinopathy
PRP laser treatment in 1990 - OCTA
Type I Diabetes with Proliferative Retinopathy
PRP laser treatment in 1990 - OCTA
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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.
Diabetic Retinopathy
Diabetic Retinopathy
Non Proliferative Diabetic Retinopathy
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:
Diabetic Retinopathy
Proliferative Diabetic Retinopathy
- 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 Retinopathy
Diabetic Macular Edema
- Follow the guidelines of the ETDRS when
considering the referral ??
- Most retina surgeons will treat “center involved”
diabetic macular edema
Referral Criteria:
Diabetic Retinopathy
Referral Criteria:
Diabetic Macular Edema
Center versus non center involved edema…..