The Diabetic Retinopathy Clinical
Research Network
Dedicated to multicenter clinical research of diabetic
retinopathy, macular edema and associated conditions
Supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes
and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services
EY14231, EY018817
DRCR.net Overview


Objective:
• The development of a collaborative network
to facilitate multicenter clinical research on
diabetic retinopathy, DME and associated
conditions.
Funding:
• National Eye Institute (NEI) and The
National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK)-sponsored
cooperative agreement initiated September
2002.
o Current award 2014-2018
2
Priority Initiatives
 Involvement of community-based practices, as
well as “academic” or university-based
centers.
 Collaborate with industry to facilitate
investigations and pursue opportunities
otherwise not possible and to do so in a
manner consistent with the Network’s
dedication to academic integrity and optimal
clinical trial performance.
3
DRCR.net Status
(as of 1/6/14)
Active
Total
119
179
80 (67%)
120 (67%)
Investigators
Other Personnel
363
979
786
2746
States
37
41
Sites
(Community & Academic Centers)
Community Sites
4
How to Join the Network
All retina specialists are welcome to
apply
 E-mail drcrnet@jaeb.org
 Your request will be reviewed and if
approved the necessary paperwork
will be sent to you

5
How to Submit a Protocol Idea





Go to the public* website: drcr.net
Click on Information for Investigators.
Scroll down to Protocol Idea Form.
E-mail form to drcrnet@jaeb.org
It will be reviewed by the Operations Group at
the next in-person meeting.
* Forms also available on the study website
6
DRCR Network Completed Protocols
(as of 2/12/14)
Protocol
# of
Subjects
I: Laser-Ranibizumab-Triamcinolone Study for DME
691
J: Laser-Ranibizumab-Triamcinolone Study for DME + PRP
333
K: The Course of Response to Focal Photocoagulation for DME
128
L: Autorefraction and E-ETDRS Measurements in DME
490
N: Intravitreal Ranibizumab for Vitreous Hemorrhage from PDR Study
261
O: Comparison of Time Domain OCT & Spectral Domain OCT in DME
1183
P: Pilot Study of Individuals with DME Undergoing Cataract Surgery
68
Q: Individuals with Diabetes without DME Undergoing Cataract Surgery
317
R: NSAIDs in Eyes with Non Central Involved DME
125
7
DRCR Network Ongoing Protocols
(as of 2/12/14)
Protocol
# of
Subjects
M: Diabetes Education Study*
1875
S: Prompt PRP vs. Ranibizumab + Deferred PRP for DPR*
305
T: Anti-VEGF comparison*
660
U: Phase II Persistent DME Study**
V: Very Good Visual Acuity**
39
Genetics Ancillary Study: Genes in Diabetic Retinopathy**
855
DRCR Network Participant Total Since 2003
8807
8
* Enrollment done/in active follow-up; **Recruiting
What Has Been Learned?
Diabetic Macular Edema Treatment



Protocol B: Over 2 years, focal/grid photocoagulation is
more effective and has fewer side effects than 1 mg or
4 mg doses of preservative-free intravitreal triamcinolone.
Protocol E: In cases of DME with good visual acuity,
peribulbar triamcinolone, with or without focal
photocoagulation, is unlikely to be of substantial benefit.
Protocol H: The results demonstrated that intravitreal
bevacizumab can reduce DME in some eyes, but the study
was not designed to determine whether the treatment was
beneficial.
9
What Has Been Learned?
Diabetic Macular Edema Treatment


Protocol I: Intravitreal ranibizumab with prompt or
deferred (≥24 weeks) focal/grid laser is more effective
through 2 years in increasing visual acuity compared with
focal/grid laser treatment alone for the treatment of DME
involving the central macula. Ranibizumab should be
considered for patients with DME and decreased visual
acuity.
Protocol K: Sixteen weeks after focal/grid laser for DME in
eyes with a definite reduction, but not resolution, of
central edema, 23% to 63% likely will continue to improve
without additional treatment.
10
What Has Been Learned?
Diabetic Retinopathy Treatment


Protocol F: Results suggest that clinically meaningful
differences are unlikely in OCT thickness or visual acuity
following application of PRP in 1 sitting compared with 4
sittings. These results suggest PRP costs to some patients
in terms of travel and lost productivity as well as to eye
care providers could be reduced.
Protocol J: The addition of 1 intravitreal triamcinolone
injection or 2 intravitreal ranibizumab injections in eyes
receiving focal/grid laser for DME and PRP is associated
with better visual acuity and decreased macular edema by
14 weeks. Whether continued long-term intravitreal
treatment is beneficial cannot be determined from this
study.
11
What Has Been Learned?
OCT and Retinal Thickening



Protocol C: Although on average there are slight decreases in
retinal thickening during the day, most eyes with diabetic
macular edema have little meaningful change in OCT central
subfield thickening or visual acuity between 8 AM and 4 PM.
Protocol C: Reproducibility of retinal thickness in DME was
better for central subfield thickness measurements than for
center point measurements. A change in central subfield
thickness exceeding 11% is likely to be real.
Protocol G (Secondary Outcomes): While subclinical DME
may be uncommon, this study suggests that between
approximately one-quarter and one-half of eyes with
subclinical DME will progress to more definite thickening or
be judged to need treatment for DME within 2 years after its
identification.
12
What Has Been Learned?
Optical Coherence Tomography


Protocol G (Primary Outcomes): CSF thickness on Stratus
OCT™ in people with diabetes and minimal or no retinopathy
are similar to thicknesses reported from a normative
database of people without diabetes. CSF thickness is
greater in men than in women. Studies involving
comparisons of retinal thickness to expected norms should
consider different mean values for women and men.
Protocol O: Mean CSF thickness is ~70 µm thicker when
measured with Heidelberg Spectralis OCT as compared with
Stratus OCT among individuals with diabetes in the absence
of retinopathy or with minimal non-proliferative retinopathy
and a normal macular architecture. CSF thickness values
≥320 µm for men and 305 µm for women are proposed as
gender-specific thickness levels.
13
What Has Been Learned?
Optical Coherence Tomography

Protocol O: Conversion equations may be used to transform
CSF values obtained on a SD-OCT to a TD scale for group
comparisons. However, the CSF conversion equations do
not appear to predict TD values for an individual accurately
enough to warrant use of these conversion equations
confidently in clinical decision-making at the patient level.
14
Recently Completed Protocols
15
Protocol I: Intravitreal Ranibizumab
or Triamcinolone Acetonide in
Combination with Laser
Photocoagulation for Diabetic
Macular Edema
16
Objective
• To evaluate the safety and efficacy of intravitreal antiVEGF treatment in combination with immediate or
deferred focal/grid laser photocoagulation and
intravitreal corticosteroids in combination with
focal/grid laser compared with focal/grid laser alone
in eyes with center-involved DME
Major Eligibility
Criteria
• Diabetic macular edema involving the center of the
macula (OCT central subfield thickness ≥ 250
microns) responsible for visual acuity of 20/32 or
worse
Protocol Status
• Total enrolled (3/07-12/08): 691 subjects/854 eyes at
52 sites
• Final 5 year visit December 2013
Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or
deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 17
June;117(6):1064-1077.e35.
Change in Visual Acuity from Baseline (letter score)
Mean Change in Visual Acuity*
at Follow-up Visits
Sham+Prompt Laser
Ranibizumab+Prompt Laser
Ranibizumab+Deferred Laser
Triamcinolone+Prompt Laser
11
10
9
8
7
N = 626 (52 weeks)
N = 600 (68 weeks)
N = 600 (84 weeks)
N = 628 (104 weeks)
6
5
4
3
2
1
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 100104
Visit Week
*Truncated to ± 30 letters
P-values for difference in mean change in VA from sham+prompt laser at the 104 week visit:
ranibizumab+prompt laser =0.03; ranibizumab+deferred laser <0.001; and triamcinolone+prompt laser=0.35.
18
Injections Prior to 3 Year*
Maximal number of injections
prior to 3- year visit
Ranibizumab
+ Prompt
Laser
N=144
Ranibizumab
+ Deferred
Laser
N=147
39
39
*Only eyes that completed 3 year visit
19
Injections Prior to 3 Year*
Ranibizumab
+ Prompt
Laser
N=144
Ranibizumab
+ Deferred
Laser
N=147
Maximal number of injections
prior to 3- year visit
39
39
Median number of injections
in year one (1st / 2nd 6 months)
8 (6/3)
9 (6/3)
*Only eyes that completed 3 year visit
20
Injections Prior to 3 Year*
Ranibizumab
+ Prompt
Laser
N=144
Ranibizumab
+ Deferred
Laser
N=147
Maximal number of injections
prior to 3- year visit
39
39
Median number of injections
in year one (1st / 2nd 6 months)
8 (6/3)
9 (6/3)
2
3
Median number of injections
in year two
*Only eyes that completed 3 year visit
21
Injections Prior to 3 Year*
Ranibizumab
+ Prompt
Laser
N=144
Ranibizumab
+ Deferred
Laser
N=147
Maximal number of injections
prior to 3- year visit
39
39
Median number of injections
in year one (1st / 2nd 6 months)
8 (6/3)
9 (6/3)
Median number of injections
in year two
2
3
Median number of injections
in year three
1
2
Median number of injections
prior to 3 year visit
12
15
*Only eyes that completed 3 year visit
22
Focal/Grid Laser Prior to 3 Years*
Ranibizumab
+ Prompt
Laser
N = 144
Ranibizumab
+ Deferred
Laser
N = 147
Maximal possible number of
focal/grid laser treatments
prior to 3-year visit
12
10
Median number of focal/grid
laser treatments from baseline
to (prior to) 3-year visit
3
0
100%
46%
% of eyes that received
focal/grid laser treatments
from baseline to (prior to) 3year visit
* Only eyes that completed 3-year visit
23
Mean Change in Visual Acuity*
at Follow-up Visits
Change in Visual Acuity from Baseline (Letter
Score)
12
Ranibizumab + Prompt Laser N = 338 (52 weeks)
10
Ranibizumab + Deferred
Laser
N = 317 (104 weeks)
N = 291 (156 weeks)
8
6
4
2
0
Visit Week
*Truncated to ± 30 letters
52
156
104
24
Change in Visual Acuity*
Change in Visual
Acuity (letters)**
2-years
(Estimated
Means)
3- Years
(Estimated
Means)
Ranibizumab
+
Prompt
Laser
N = 144
+7.2
+6.8
Ranibizumab
+
Deferred
Laser
N = 147
Estimated
Difference (B
vs. C) (95% CI)
[P-Value]
+9.0
-1.8 (-3.6
to +0.1)
[P = 0.06]
+9.7
-2.9 (-5.4
to -0.4)
[P = 0.02]
*Visits occurring between 980 and 1204 days from randomization were included as 3 year visits
**truncated to ± 30 letters, based on longitudinal analyses adjusting for baseline VA
25
Visual Acuity Gain at 3 Years
Proportion of Visual Acuity Change
100%
90%
80%
≥15 letter loss
10-14 letter loss
5-9 letter loss
within ±4
9-5 letter gain
14-10 letter gain
70%
60%
50%
40%
30%
≥15 letter gain
20%
10%
0%
Ranibizumab +
Prompt Laser
N = 144
Ranibizumab
+ Deferred
Laser
N = 147
26
Conclusions

Intravitreal ranibizumab with prompt or deferred
(≥24 weeks) focal/grid laser is more effective
through 2 years in increasing visual acuity
compared with focal/grid laser treatment alone
for the treatment of DME involving the central
macula. Ranibizumab should be considered for
patients with DME and decreased visual acuity.
27
Conclusions:
Ranibizumab + prompt laser vs. deferred laser



Results suggest that focal/grid laser treatment at the
initiation of intravitreal ranibizumab is no better, and
possibly worse, for vision outcomes than deferring
laser treatment for 24 weeks or more in eyes with DME
involving the fovea and with vision impairment.
Some of the observed differences in visual acuity at 3
years may be related to the fewer number of
ranibizumab injections during follow-up in the prompt
laser treatment group.
Despite the decreasing number of injections given in
the 2nd and 3rd year of management, the ranibizumab +
deferred laser treatment group showed no decline in
visual acuity, and the ranibizumab + prompt laser
treatment group showed only a slight decline from the
28
1-year to 3-year visit.
Protocol M: Effect of Diabetes
Education During Retinal
Ophthalmology Visits on
Diabetes Control
29
Objective
• Determine if glycemic control in individuals with
type 1 or type 2 diabetes can be improved with
subject-specific diabetes education and risk
assessment during office visits to a retina
specialist
Major Eligibility
Criteria
• Diagnosis of diabetes mellitus
(type 1 or type 2)
• Patient is not eligible if patient has a
known HbA1c <7.5% within prior 6 months
Protocol Status
• Recruitment: 1,875; original goal: 2,000
• Final visits currently being completed
30
Protocol R: A Phase II Evaluation of
Topical NSAIDs in Eyes with Non
Central Involved DME
31
Objective
• To assess the effects of topical NSAIDs on
macular retina volume compared with placebo in
eyes with non-central DME
• To assess the effects of topical NSAIDs on
central subfield thickness and to compare the
progression of non-central DME to central DME
as determined by OCT and stereoscopic fundus
photographs
Major Eligibility
Criteria
• Best corrected E-ETDRS VA letter score ≥74
(20/25 or better)
• Definite retinal thickening due to DME within
3000 µm of the center of the macula but not
involving the central subfield
• No focal/grid laser within the last 6 months or
other treatment for DME within the last 4 months
Protocol Status
• Total enrolled: 125subjects randomized
• All follow-up visits completed.
32
Active Studies
33
Image: National Eye Institute, National Institutes of Health
Protocols in Follow-up
34
Protocol S: Prompt PRP versus Intravitreal
Ranibizumab with Deferred PRP for PDR

Objective
• To determine if visual acuity outcomes at
2 years in eyes with PDR that receive antiVEGF therapy with deferred PRP are noninferior to those in eyes that receive
standard prompt PRP therapy.
35
Image: National Eye Institute, National Institutes of Health
Protocol S: Prompt PRP versus Intravitreal
Ranibizumab with Deferred PRP for PDR

Major Eligibility Criteria
• Study eye with
o
o
o

PDR for which PRP can be safely deferred for at
least 4 weeks in the investigator’s judgment.
No prior PRP
Visual acuity letter score in the study eye > 24
(~ Snellen equivalent of 20/320 or better)
Enrollment (Completed)
• Total enrolled: 305 participants and 394
study eyes at 56 sites
36
Protocol T: A Comparative
Effectiveness Study of Intravitreal
Aflibercept, Bevacizumab and
Ranibizumab for DME
37
Image: National Eye Institute, National Institutes of Health
Study Objective and Treatment
Arms (N = 660)
To compare the efficacy and safety of
(1) intravitreal aflibercept, (2) intravitreal
bevacizumab, and (3) intravitreal ranibizumab
when given to treat central-involved DME in
eyes with visual acuity of 20/32 to 20/320.
2.0 mg
intravitreal
aflibercept
1.25 mg
intravitreal
bevacizumab
0.3 mg
intravitreal
ranibizumab
Major Inclusion Criteria



Age ≥18 years
Type 1 or 2 diabetes
Study eye:
•
•
•
Visual acuity (~Snellen equivalent) 20/32 or worse
and 20/320 or better
Definite retinal thickening due to central-involved
DME on clinical exam
OCT CSF ≥ OCT-machine gender specific cut-off for
definite central involved DME
Follow-up Schedule
Baseline to
1 Year
Optional Visit
2-3 Days after 1st
2nd or 3rd visit
1 Year to 2 Years
• Visits every 4 weeks
• Primary outcome at 1 year
• Urine sample
• Blood pressure (another BP
measurement will be taken at the
first 4 week visit after the optional
visit)
• Visits every 4 to 16 weeks
• Depends on disease status and
treatment
Protocols Currently
Enrolling
41
Protocol V
Very Good Visual Acuity
42
Protocol V - Treatment for Centralinvolved DME in Eyes with Very
Good Visual Acuity
Objective: compare the safety and efficacy of 1) prompt
laser with deferred anti-VEGF, 2) observation with deferred
anti-VEGF, and 3) prompt anti-VEGF in eyes with center
involved DME and good vision (defined as visual acuity 
20/25).
 Primary Outcome: proportion of eyes with a visual loss
of at least 5 letters at 1 year, confirmed at 2
consecutive 4-week visits
43
Study Design
Randomized, multi-center clinical trial
At least one eye meeting all of the following criteria:
• Central-involved DME on OCT (Cirrus/Spectralis only)*
• VA letter score 20/25 or better*
• No prior treatment for DME
Prompt
anti-VEGF
Prompt laser +
deferred anti-VEGF
Observation +
deferred anti-VEGF
Primary outcome: Proportion of eyes that have lost ≥5
letters of VA at 2 years
*Confirmed at 2 visits (screening and randomization 1-28 days apart)
44
Outcome Measures

Primary Outcome


% with VA loss of ≥ 5 letters at 2 years
Secondary Outcomes









Mean change in VA letter score
% with at least 10 and 15 letter VA gain/loss
Visual acuity area under the curve
Mean change in OCT CSF thickness
% with 1 or 2 log step gain or loss on OCT
Number of injections/lasers performed
Worsening/improvement of DR severity level
Low contrast visual acuity
Safety outcomes
45
Major Eligibility Criteria


Type 1 or 2 diabetes
Study Eye:
•
•
•
•

Central-involved DME on clinical exam, confirmed
on OCT at two consecutive visits (1-28 days apart)
VA letter score >79 (~20/25 or better) at two
consecutive visits (1-28 days apart)
The investigator is comfortable with the eye being
randomized to any of the three treatment groups
No history of prior DME treatment
Non-study eye:
•
Investigator must be willing to use (or switch to
using) study aflibercept on the non-study eye if
needed
46
Major Exclusion Criteria

Systemic
•
•
•

History of chronic renal failure requiring dialysis or kidney
transplant
Initiation of intensive insulin treatment (a pump or multiple
daily injections) within 4 months prior to randomization or
plans to do so in the next 4 months
BP > 180/110
Study eye
•
•
•
Macular edema not due to DME (eyes with thickening due
to ERM, prior cataract surgery or other non-DME reason
should not be enrolled)
PRP in last 4 months or anticipated in next 6 months
History of or anticipated need for intravitreal anti-VEGF for
an ocular condition other than DME
47
Follow-Up Schedule


Total follow-up through 2 years
Visit schedule will vary by treatment group and
disease progression
•
•

Prompt anti-VEGF group: visits every 4 weeks through
24 weeks, then every 4 to 16 weeks depending on
whether injections are being given
Deferred groups (observation and laser groups): visits
at 8 and 16 weeks, then every 16 weeks unless vision
and/or OCT are worsening or anti-VEGF is initiated
(visits every 4, 8 or 16 weeks depending on disease
progression and treatment)
All participants will have visits at 1 and 2 years
48
Protocol U
Short-term Evaluation of Combination
Corticosteroid+Anti-VEGF Treatment
for Persistent CI-DME Following AntiVEGF Therapy in Pseudophakic Eyes
49
Objectives


To assess short-term effects of combination
steroid+anti-VEGF therapy on OCT retinal thickness
and visual acuity in comparison with that of
continued anti-VEGF therapy alone in pseudophakic
eyes with persistent DME and visual acuity
impairment despite previous anti-VEGF treatment.
To provide more information needed for future
conduct of a definitive phase III clinical trial.
50
Study Design
 Phase
II, multicenter, controlled,
participant-masked, clinical trial

Duration of Follow-up
Run-in Phase
12 Weeks
Purpose
To ensure that enrolled
eyes truly have
“persistent DME” with
decreased visual
acuity despite prior
anti-VEGF therapy.
Randomized Phase
24 Weeks
51
Study Overview
SHM
SHM
VGF
VGF
Week
0
VGF
Week
4
VGF
Week
8
VGF
Week
12
VGF
Week
16
Week
20
Week
24
Group A: Sham + Ranibizumab
VGF
VGF
Week 0
Week 4
VGF
Week 8
Week
12
Group B: Dexamethasone+ Ranibizumab
Enrollment
Week
0
VGF
Dex
Run-In Phase (3 months)
Assess
Eligibility For
Randomization
Week
4
VGF
Week
8
VGF
Week
12
VGF
Week
16
VGF
Week
20
Week
24
VGF
Dex
Randomization Phase (6 months)
52
Major Eligibility Criteria






Age ≥18 years
Type 1 or type 2 diabetes
At least 1 eye meeting study eye eligibility
criteria
No history of chronic renal failure requiring
dialysis or kidney transplant
BP <180/110
No history of cardiac event
or stroke within 1 month
prior to enrollment
53
Major Study Eye Eligibility Criteria







Pseudophakic
At least 6 injections of anti-VEGF drugs (aflibercept,
bevacizumab, or ranibizumab) within the prior 36
weeks (9 months)
Visual acuity letter score ≤78 and ≥24 (20/32 to 20/320)
Central-involved DME on clinical exam
OCT CSF thickness within 8 days of enrollment

≥340 on Zeiss Cirrus

≥360 on Zeiss Stratus
No macular laser or PRP within 4 months or
anticipated need for PRP in next 6 months
No previous history of glaucoma or steroid intraocular
pressure response in either eye
54
Efficacy Outcomes at 24 Weeks

Primary:
•

Mean change in visual acuity letter score adjusted for
baseline (randomization)
Secondary:
•
Visual Acuity
o
o
•
OCT
o
o
o
o
•
% of eyes with ≥10 and ≥15 letter increase or decrease
Area under the curve (AUC) from baseline
Change in CSF thickness adjusted for baseline
% ≥2 logOCT step gain or loss in CSF
CSF thickness < spectral-domain value equivalent to 250
microns on Zeiss Stratus
AUC from baseline
Diabetic Retinopathy worsening or improvement on clinical
exam
55
Genetics
Genes in Diabetic Retinopathy Project
56
Genes in Diabetic Retinopathy Project
Objective
• To create a repository of genetic material and
clinical phenotype information as a resource for
the research community
• The database may provide the opportunity to
assess genetic susceptibility and resistance to
DR and also variants impacting visually-important
biomarkers for ME and neovascularization.
 Major Eligibility Criteria
• Previous or current participant in a DRCR.net
study
 Enrollment (Ongoing)
57
• Total enrolled: 855 subjects (as of 2/13/14)

Protocols In Development
58
Protocol AA: Peripheral Diabetic Retinopathy
(DR) Lesions on Ultrawide-field Fundus
Images and Risk of DR Worsening Over Time
59
Objectives

Primary objective
•
•
In general to assess whether there are
factors in the retinal periphery that are
associated with rate of DR worsening over
time.
Specifically, the primary factor of interest is
to assess whether predominance versus
non-predominance of DR lesions in the
retinal periphery is associated with rates of
DR worsening over time
60
Study Design & Eligibility Criteria



Prospective, observational longitudinal study
Follow-up: Annually for 4 years
Enrollment Criteria
•
Adults with Type 1 or type 2 diabetes
NPDR (ETDRS level 35 - 57) based on modified 7 field
ETDRS grading.
No history of PRP or Vitrectomy
Eyes not previously treated with intravitreal agents over
prior 12 months and treatment not anticipated for next 6
months
o Enrollment will be limited to only 50% of the cohort
with any prior intravitreal anti-VEGF or steroid for
DME.
•
No DME in the central subfield
•
•
•
61
Outcomes

Longitudinal Analysis
•
•
Relative risk of 2 or more step worsening of DR
severity over 4 years in the groups with and without
predominantly peripheral lesions on UWF images at
baseline.
Secondary analysis - additional risk factors including:
o
o
o
•
Type of peripheral lesions
Location of peripheral lesions
Extent of peripheral non-perfusion on FA
Secondary outcomes include the evaluation of risk
factors for the progression to PDR, improvement of
DR, improvement, worsening, or development of DME,
and development of VH.
62
Outcomes

Cross Sectional Analysis at Baseline
•
Level of agreement between DR or DME severity as
graded on UWF vs DRCR.net protocol images
•
% and type of peripheral lesions identified on UWF
images not seen on DRCR.net protocol images
•
% of time peripheral lesions seen on UWF images
outside the 7 std fields could change level of ETDRS
DR severity
63
Sample Size



Projected to Begin Q2 2014
Estimated 40 sites will
participate
Within each primary cohort,
o
o
o
~40% w/ mild NPDR
(ETDRS levels 35)
~40% w/ moderate or
moderately severe NPDR
(ETDRS levels 43-47)
~20% w/ severe NPDR
(ETDRS level 53)
Predominantly
Peripheral
Lesions
NOT
Predominantly
Peripheral
Lesions
64
The Diabetic Retinopathy Clinical
Research Network
Thank you
65