Randomized Trial Evaluating Ranibizumab
Plus Prompt or Deferred Laser or
Triamcinolone Plus Prompt Laser for
Diabetic Macular Edema:
Potential impact of Clinically Relevant Subgroups
from DRCR.net Treatments of DME
Scott M. Friedman, MD
1
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, EY14229, EY018817
Disclosures
 Presenter Financial Disclosures: I am a clinical
investigator working on trials supported by Genentech,
Allergan, Neovista, Thrombogenics, and Glaxo-SmithKline. I receive no income from these companies other
than through the participation in these clinical trials.
 Data from human research is presented
 Genentech (provided the ranibizumab) and Allergan, Inc.
(provided the triamcinolone) for the study and
collaborated in a manner consistent with the DRCR.net
Industry Collaboration Guidelines, the DRCR.net had
complete control over the design of the protocol,
ownership of the data, and all editorial content of
presentations and publications related to the protocol.
2
Subgroup Analyses
 To examine potential differences in treatment
group effects among baseline subgroups, the
following were analyzed:
•
•
•
•
•
Prior treatment for DME
Baseline visual acuity
Baseline OCT-measured central subfield thickening
Baseline level of diabetic retinopathy on photos
Description of edema by ophthalmologist as
predominantly focal or predominantly diffuse
• Pseudophakic at baseline
3
Change in Visual Acuity at 1 Year
Stratified by Baseline Visual Acuity
N=146
4
Change in Visual Acuity at 1 Year
Stratified by Baseline CST
5
Change in Visual Acuity at 1 Year
Stratified by Prior DME Treatment
6
Change in Visual Acuity at 1 Year Stratified by Eyes
with Diffuse vs. Focal Edema at Baseline as Graded
by Study Ophthalmologist
7
Change in Visual Acuity at 1 Year Stratified by
Retinopathy Severity at Baseline
Mean Change in Visual Acuity (letter
score) from Baseline
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0
N=109
N=113
Sham
+Prompt Laser
N=64
N=74
Ranibizumab
+Prompt Laser
N=81
N=178
Ranibizumab
+Deferred Laser
N=99
N=100
Triamcinolone
+Prompt Laser
Moderately severe NPDR
or better
Severe NPDR or worse
8
Change in Visual Acuity at 1 Year
Stratified by Pseudophakic at Baseline
Mean Change in Visual Acuity (letter
score) from Baseline
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0
Sham
+Prompt Laser
N=134
N=131
N=56
N=62
N=54
Ranibizumab
+Deferred
Laser
Triamcinolone
+Prompt Laser
N=101
N=192
N=124
No
Ranibizumab
+Prompt Laser
Yes
Pseudophakic at Baseline
9
Mean Change in Visual Acuity at Follow-up Visits
among Eyes that were
Pseudophakic at Baseline*
Visit Week
* Values that were ±30 letters were assigned a value of 30
10
≥10 Letter Visual Acuity Improvement/Worsening
among Eyes Not Pseudophakic and Eyes that were
Pseudophakic at Baseline
Eyes not Pseudophakic at Baseline
Eyes Pseudophakic at Baseline
11
Discussion
12
Subgroup Analyses
Summary
 No obvious clinically important difference in
results at 1-year primary outcome visit for any
of the following subgroups:
•
•
•
•
•
Prior treatment for DME
Baseline visual acuity
Baseline OCT-measured central subfield thickening
Baseline level of diabetic retinopathy on photos
Description of edema by ophthalmologist as
predominantly focal or predominantly diffuse
 In the subset of pseudophakic eyes at baseline
(n = 273), visual acuity improvement in the
triamcinolone+prompt laser group appeared
comparable to the ranibizumab groups
13
Subgroup Analysis
Summary
 In pseudophakic eyes, intravitreal triamcinolone with
prompt focal/grid laser seems more effective than laser
alone
 These results are in contrast with a similar group of eyes
treated with intravitreal triamcinolone without prompt
focal/grid laser (DRCR.net Protocol B: Laser vs. Intravitreal
Triamcinolone for DME)
•
•
•
Pseudophakic eyes at baseline were not superior using intravitreal
triamcinolone compared to focal/grid laser
Differences in outcome may be due to differences in characteristics of
eyes between these 2 studies
Logical to assume that combination of 2 monotherapies (focal/grid laser &
intravitreal triamcinolone) for DME in pseudophakic eyes is superior to
focal/grid laser alone, although this was not true for entire cohort which
included phakic eyes
Protocol B and Protocol I
comparison
 Protocol B
• Pseudophakic eyes at baseline treated
with intravitreal triamcinolone
compared to focal/grid laser did not
have superior outcomes
 Protocol I subgroup analysis
• In pseudophakic eyes, intravitreal
triamcinolone with prompt focal/grid
laser seems more effective than laser
alone
Subgroup Analysis
Conclusion
 In pseudophakic eyes, intravitreal
triamcinolone with prompt focal/grid laser may
be equally effective as ranibizumab at
improving visual acuity and reducing retinal
thickening, and associated with fewer
injections, but also associated with an
increased risk of intraocular pressure
elevation.
16
Thank You on Behalf of Diabetic Retinopathy
Clinical Research Network (DRCR.net)
 52 clinical study sites
 Study participants who volunteered to participate in this
trial
 DRCR.net Data and Safety Monitoring Committee
 Genentech (provided the ranibizumab) and Allergan, Inc.
(provided the triamcinolone) for the study and collaborated
in a manner consistent with the DRCR.net Industry
Collaboration Guidelines, the DRCR.net had complete
control over the design of the protocol, ownership of the
data, and all editorial content of presentations and
publications related to the protocol.
 DRCR.net investigators and staff (www.drcr.net)
17