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 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 1
Transcript
Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or
Triamcinolone Plus Prompt Laser for Diabetic Macular Edema:
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
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
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DisclosuresDisclosures Presenter Financial Disclosures: I am a clinical
investigator working on trials supported by Genentech, Allergan, Neovista, Thrombogenics, and Glaxo-Smith-Kline. 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.
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Subgroup AnalysesSubgroup 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
Change in Visual Acuity at 1 Year Stratified by Baseline Visual AcuityChange in Visual Acuity at 1 Year
Stratified by Baseline Visual Acuity
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N=146
Change in Visual Acuity at 1 Year Stratified by Baseline CST
Change in Visual Acuity at 1 Year Stratified by Baseline CST
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Change in Visual Acuity at 1 Year Stratified by Prior DME TreatmentChange in Visual Acuity at 1 Year Stratified by Prior DME Treatment
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Change in Visual Acuity at 1 Year Stratified by Eyes with Diffuse vs. Focal Edema at Baseline as Graded
by Study Ophthalmologist
Change in Visual Acuity at 1 Year Stratified by Eyes with Diffuse vs. Focal Edema at Baseline as Graded
by Study Ophthalmologist
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Change in Visual Acuity at 1 Year Stratified by Retinopathy Severity at Baseline
Change in Visual Acuity at 1 Year Stratified by Retinopathy Severity at Baseline
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0
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Moderately severe NPDR or better
Severe NPDR or worse
Mea
n C
han
ge
in V
isu
al A
cuit
y (l
ette
r sc
ore
) fr
om
Bas
elin
e
Sham +Prompt Laser
Ranibizumab +Prompt Laser
Ranibizumab +Deferred Laser
Triamcinolone +Prompt Laser
N=178
N=109
N=113
N=99
N=100
N=74
N=64
N=81
Change in Visual Acuity at 1 Year Stratified by Pseudophakic at Baseline
Change in Visual Acuity at 1 Year Stratified by Pseudophakic at Baseline
Mean Change in Visual Acuity at Follow-up Visits among Eyes that were
Pseudophakic at Baseline*
Mean Change in Visual Acuity at Follow-up Visits among Eyes that were
Pseudophakic at Baseline*
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Visit Week
* Values that were ±30 letters were assigned a value of 30
≥10 Letter Visual Acuity Improvement/Worsening among Eyes Not Pseudophakic and Eyes that were
Pseudophakic at Baseline
≥10 Letter Visual Acuity Improvement/Worsening among Eyes Not Pseudophakic and Eyes that were
Pseudophakic at Baseline
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Eyes not Pseudophakic at Baseline Eyes Pseudophakic at Baseline
DiscussionDiscussion
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Subgroup AnalysesSummary
Subgroup AnalysesSummary
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
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
Subgroup AnalysisSummary
Protocol B and Protocol I comparison
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
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Subgroup AnalysisConclusion
Subgroup AnalysisConclusion
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.
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Thank You on Behalf of Diabetic Retinopathy Clinical Research Network (DRCR.net)
Thank You on Behalf of Diabetic Retinopathy Clinical Research Network (DRCR.net)
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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.
