1. Diabetic Retinopathy Clinical Research Network
Comparative Effectiveness Study of Aflibercept, Bevacizumab, or Ranibizumab for DME
Supported through a cooperative agreement from the
National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health, Department of Health and Human Services EY14231, EY14229, EY018817  1

2. Disclosure
Funding/Support: Cooperative Agreement with NEI and NIDDK of NIH, U.S. Department of Health and Human Services.
Additional Contributions: Regeneron Pharmaceuticals, Inc. provided the aflibercept; Genentech Inc. provided the ranibizumab. Genentech Inc. also provided funding for blood pressure cuffs and collection of plasma and urine that are not part of the main study reported herein.
A complete list of all DRCR.net investigator financial disclosures can be found at

3. Background
Diabetic macular edema (DME) affects ~750,000 people in the U.S.
Intravitreous anti-vascular endothelial growth factor (anti-VEGF) injections of either aflibercept (EYLEA), bevacizumab (Avastin), or ranibizumab (Lucentis) are effective in treating DME.
The relative efficacy and safety of these agents within a head-to-head study were unknown prior to the results of this trial

4. Background
Aflibercept and ranibizumab are FDA approved for DME treatment.
Bevacizumab is not FDA approved for intraocular use,
used “off-label” for DME treatment and
repackaged into aliquots ~1/500 of systemic dose in cancer treatments.
Medicare allowable charges:
Aflibercept (2.0 mg): $1961
Bevacizumab (repackaged 1.25mg): $67
Ranibizumab (0.3 mg): $1189

5. Primary Objective
For eyes with center involved DME with decreased visual acuity, compare one year efficacy and safety of,
intravitreous aflibercept (EYLEA®),
intravitreous bevacizumab (Avastin®) and
intravitreous ranibizumab (Lucentis®)

6. Randomized, multi-center clinical trial (N = 89 Sites)
Study Design
Randomized, multi-center clinical trial (N = 89 Sites)
Participants meeting all of the following criteria:
At least 18 years old
Type 1 or type 2 diabetes
Study eye meeting all of the following criteria:
~Snellen equivalent visual acuity 20/32 or worse and 20/320 or better
Central-involved DME on clinical exam
Central subfield (CSF) thickness ≥ protocol-defined gender and optical coherence tomography (OCT) machine-specific thresholds
No history of an anti-VEGF treatment for DME in the past 12 months or any other DME treatment in the past 4 months
Primary Outcome: Change in visual acuity at one year adjusted for baseline visual acuity using the intent-to-treat principle

7. Pre-Planned Subgroup Analyses
Preplanned subgroup analyses included only:
Baseline visual acuity
Baseline OCT Central Subfield Thickness
Any Prior Anti-VEGF treatment
Lens Status

8. Follow-up Schedule Visit Procedures
Baseline to
1 year
Visits every 4 weeks
Primary outcome at 1 year
Visit Procedures
Refraction with Electronic-ETDRS visual acuity measurement
OCT spectral domain (97%) or time domain
Dilated ocular exam
Color fundus photos (baseline/1 year only)
ETDRS = Early Treatment Diabetic Retinopathy Study

9. Treatment Schedule Through 1 Year (q4 weeks)
Repeat injections at every 4-week visit if eye “improved”* or “worsened”*
Otherwise, defer injections if either:
Visual acuity 20/20 or better and OCT CST “normal” or,
At or after 24 weeks, visual acuity and OCT stable after 2 consecutive injections
Resume injections if VA or OCT worsened*
*Improved/worsened defined as:
≥ 5 letter change (~1 Snellen line) from last injection, or,
≥ 10% CST change on OCT from last injection

10. Treatment Schedule Through 1 Year
Focal/grid laser: initiated at or after 24 weeks only if persistent DME not improving after at least 2 injections

11. Randomization Randomly Assigned Eyes (one per participant): N = 660
Aflibercept (2.0 mg)
N = 224
Bevacizumab (1.25 mg)
N = 218
Ranibizumab
(0.3 mg)
N = 218
Baseline
N = 208 (93%)
N = 206 (94%)
N = 206 (94%)
One Year
One Year Excluding Deaths
94%
97%
96%

12. Baseline Characteristics
Aflibercept
(N = 224)
Bevacizumab
(N = 218)
Ranibizumab
Age (years) – Median 61 63 59
Gender: Women
49%
47%
43%
Race
White
65%
64%
67%
Black/African American
14%
17%
Hispanic
Other 4% 3%
Type 2 diabetes
88%
94%
90%
Median HbA1c
7.6
7.7
7.8

13. Ocular Baseline Characteristics
Aflibercept
(N = 224)
Bevacizumab
(N = 218)
Ranibizumab
Mean visual acuity letter score
(~Snellen Equivalent) 56
(20/80) 57
Mean OCT CST (µm)
387
376
390
Any Prior Focal/Grid Laser
36%
39%
37%
Any Prior Treatment with anti-VEGF
11%
14%
13%
Phakic
74%
73%
79%

14. Ocular Baseline Characteristics
Aflibercept
(N = 224)
Bevacizumab
(N = 218)
Ranibizumab
Diabetic Retinopathy Severity (ETDRS Level)*
Absent or minimal NPDR (Level 10-20) 3% 2%
Mild to moderately severe NPDR (Level 35, 43,47)
68%
62%
67%
Severe NPDR (Level 53) 8% 7%
Prior PRP; without current PDR (Level 60)
10%
Mild to moderate PDR (Level 31 and 65)
13%
15%
11%
High Risk PDR (Level 71 and 75) 1% 9%
*Missing: aflibercept (3), bevacizumab (7), and ranibizumab (2)

15. Treatment for Diabetic Macular Edema

16. DME Treatment Through 1 Year: anti-VEGF and Laser
Aflibercept
N = 208
Bevacizumab
N = 206
Ranibizumab
P-Value
# of Injections (Max = 13)
Mean
9.2
9.7
9.4
Median
(25th, 75th percentile)
9 (8, 11)
10 (8, 12)
10 (8, 11) 
0.045†
At least one focal/grid laser
37%
56%
46%
<0.001‡
†Global (overall 3 group comparison) P-value. Pairwise comparisons (adjusted for multiple comparisons): aflibercept-bevacizumab: P = 0.045, aflibercept-ranibizumab: P = 0.19, bevacizumab-ranibizumab: P = 0.22.
‡Global (overall 3 group comparison) P-value. Pairwise comparisons (adjusted for multiple comparisons): aflibercept-bevacizumab: P<0.001, aflibercept-ranibizumab: P = 0.058, bevacizumab-ranibizumab: P =

17. Efficacy

18. Mean Change in Visual Acuity Letter Score, Full Cohort
52 Week Treatment Group Comparison*:
Aflibercept vs. Bevacizumab P<0.001
Aflibercept vs. Ranibizumab P = 0.034
Ranibizumab vs. Bevacizumab P = 0.12
+13
+11
+10
* P-values adjusted for baseline visual acuity and multiple comparisons

19. Mean Change in Visual Acuity Letter Score Baseline Visual Acuity 20/32 to 20/40
~50% of Cohort
~+8

20. Mean Change in Visual Acuity Letter Score Baseline Visual Acuity 20/50 or Worse
~ 50% of Cohort
+19
+14
+12
1-Year Treatment Group Comparison*:
Aflibercept vs. Bevacizumab P<0.001
Aflibercept vs. Ranibizumab P =
Ranibizumab vs. Bevacizumab P = 0.21
* P-values adjusted for baseline visual acuity and multiple comparisons

21. Subgroup Analysis Baseline Best-corrected Visual Acuity
20/32-20/40
~+8
20/50 or worse
+19
+14
+12
Aflibercept
Bevacizumab
Ranibizumab

22. Visual Acuity Mean Change: Baseline to 1 Year
78-74
(20/32)
73-69
(20/40)
68-64
(20/50)
63-54
(20/63-20/80)
53-24
(20/100-20/320)
Baseline Visual Acuity Letter Score
N =
Aflibercept 54 52 36 29 37
Bevacizumab 41 63 35 38
Ranibizumab 46 59 32

23. Visual Acuity Outcomes Baseline = 20/32 to 20/40
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept vs Bevacizumab
+0.7
-1.3 to +2.7
0.69
Aflibercept vs
Ranibizumab
-0.4
-2.3 to
+1.5
Ranibizumab vs Bevacizumab
+1.1
-0.9 to
+3.1

24. Visual Acuity Outcomes Baseline = 20/32 to 20/40
>10 Letter Improvement
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept vs Bevacizumab
+6%
-9% to +21%
0.82
Aflibercept vs
Ranibizumab 0%
-13% to
+14%
0.95
Ranibizumab vs Bevacizumab
-10% to
+21%

25. Visual Acuity Outcomes Baseline = 20/32 to 20/40
>15 Letter Improvement
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept vs Bevacizumab
+2%
-7% to +11%
0.73
Aflibercept vs
Ranibizumab
+4%
-5% to
+12%
Ranibizumab vs Bevacizumab
-2%
-10% to
+7%

26. Visual Acuity Outcomes Baseline = 20/32 to 20/40
>10 Letter Worsening
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept vs Bevacizumab
+2%
-3% to +6%
0.54
Aflibercept vs
Ranibizumab
+3%
-1% to
+7%
Ranibizumab vs Bevacizumab
-1%
-4% to

27. Visual Acuity Outcomes Baseline = 20/50 or Worse
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept vs Bevacizumab
+6.5
+2.9 to +10.1
<0.001
Aflibercept vs
Ranibizumab
+4.7
+1.4 to
+8.0
0.0031
vs Bevacizumab
+1.8
-1.1 to
+4.8
0.21

28. Visual Acuity Outcomes Baseline = 20/50 or Worse
>10 Letter Improvement
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept vs Bevacizumab
+17%
+2% to +31%
0.018
Aflibercept vs
Ranibizumab
+10%
-4% to
+23%
0.20
Ranibizumab vs Bevacizumab
+7%
-6% to
+20%
0.28

29. Visual Acuity Outcomes Baseline = 20/50 or Worse
>15 Letter Improvement
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept vs Bevacizumab
+24%
+9% to +39%
<0.001
Aflibercept vs
Ranibizumab
+18%
+4% to
+32%
0.0078
Ranibizumab vs Bevacizumab
+6%
-7% to
+19%
0.34

30. Visual Acuity Outcomes Baseline = 20/50 or Worse
>10 Letter Worsening
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept vs Bevacizumab
-3%
-7% to +2%
0.56
Aflibercept vs
Ranibizumab
-1%
-5% to
+3%
Ranibizumab vs Bevacizumab
-6% to

31. Overall Mean (µm) Change in OCT CST Over Time
1-Year Treatment Group Comparison*:
Aflibercept vs. Bevacizumab P < 0.001
Aflibercept vs. Ranibizumab P = 0.036
Ranibizumab vs. Bevacizumab P = <0.001
-101
-147
-169
Thinner is decreased DME
* P-values adjusted for baseline visual acuity, OCT central subfield thickness, and multiple comparisons

32. Mean (µm) Change in OCT CST Baseline visual acuity 20/32 to 20/40
-67
-119
-129
1-Year Treatment Group Comparison*:
Aflibercept vs. Bevacizumab P <0.001
Aflibercept vs. Ranibizumab P = 0.057
Ranibizumab vs. Bevacizumab P = <0.001
Thinner is decreased DME
* P-values adjusted for baseline visual acuity, OCT central subfield thickness, and multiple comparisons

33. Mean (µm) Change in OCT CST Baseline visual acuity 20/50 or Worse
1-Year Treatment Group Comparison*:
Aflibercept vs. Bevacizumab P < 0.001
Aflibercept vs. Ranibizumab P = 0.22
Ranibizumab vs. Bevacizumab P = <0.001
-135
-176
-210
Thinner is decreased DME
* P-values adjusted for baseline visual acuity, OCT central subfield thickness, and multiple comparisons

34. OCT CSF Outcomes Baseline = 20/32-20/40
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept vs Bevacizumab
-55.8
-78.3 to
-32.9
<0.001
Aflibercept vs
Ranibizumab
-18.2
-36.9 to
+0.6
0.057
Ranibizumab vs Bevacizumab
-37.7
-59.3 to
-16.1

35. Visual Acuity Outcomes Baseline = 20/32-20/40
CSF <250 µm
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept
vs Bevacizumab
+31%
+16% to +45%
<0.001 vs
Ranibizumab
-2%
-16% to
+12%
0.79
+33%
+17% to
+48%
0.001

36. OCT CSF Outcomes Baseline = 20/50 or Worse Treatment Group Comparisons
Difference CI P-
Value
Aflibercept vs
Bevacizumab
-85.8
to -49.7
<0.001
Ranibizumab
-18.5
-48.2 to
+11.2
0.22
-67.3 to
-33.1

37. Visual Acuity Outcomes Baseline = 20/50 or Worse
CSF <250 µm
Treatment Group Comparisons
Difference CI
P- Value
Aflibercept vs Bevacizumab
+32%
+16% to +48%
<0.001
Aflibercept vs
Ranibizumab
+16%
+3% to
+30%
0.025
Ranibizumab vs Bevacizumab
+2% to
+29%

38. Safety

39. Ocular Adverse Events through 1 Year (Study Eye)
Aflibercept
(N = 224)
Bevacizumab
(N = 218)
Ranibizumab
P-Value
No. of injections prior to 1 year
1991
2055
2011
Endophthalmitis
Inflammation†
<1%
1.0
Retinal detachment/tear
0.55
Vitreous hemorrhage 2% 4% 3%
0.35
Injection related cataract
IOP elevation‡
14% 9%
11%
0.18
†Includes anterior chamber cell/flare, choroiditis, episcleritis, iritis, vitreous cells.
‡Includes intraocular pressure increase ≥10mmHg from baseline at any visit, intraocular pressure ≥30 mmHg at any visit, or initiation of intraocular pressure-lowering medications not in use at baseline. There were no glaucoma surgeries.
IOP= Intraocular Pressure

40. Ocular Adverse Events through 1 Year (Non-Study Eye: Study Drug)
Aflibercept
(N = 129)
Bevacizumab
(N = 122)
Ranibizumab
(N = 121)
No. of injections prior to 1 year
753
841
766
Endophthalmitis
<1%
Inflammationǁ 2%
Retinal detachment/tear
Vitreous hemorrhage 4% 7%
Injection related cataract
Intraocular pressure elevation‡
12% 9%
ǁIncludes anterior chamber cell/flare, choroiditis, episcleritis, iritis, vitreal cells.
‡Includes intraocular pressure increase ≥10mmHg from baseline at any visit, intraocular pressure ≥30 mmHg at any visit, or initiation of intraocular pressure-lowering medications not in use at baseline. There were no glaucoma surgeries.

41. Systemic Adverse Events APTC* through 1-Year
Aflibercept
(N = 224)
Bevacizumab
(N = 218)
Ranibizumab
Non-fatal MI 2%
<1% 1%
Non-fatal stroke
Vascular death
Any APTC Event 3% 4% 5%
Global P = 0.56
* Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ 1994;308:

42. Systemic Adverse Events Through 1 Year Pre-specified (Per Participant)
Aflibercept
(N = 224)
Bevacizumab
(N = 218)
Ranibizumab
P-Value*
Death (any cause) 1% 2%
0.72
Hospitalization
21%
18%
22%
0.51
SAEs
26%
25%
0.40
Gastrointestinal †
20%
17%
0.84
Kidney Events‡
13%
11%
0.81
Hypertension Events
12% 7%
0.20
*Global (overall 3 group comparison) P-value from Fisher’s Exact Test.
†Includes events with a Medical Dictionary for Regulatory Activities system organ class of gastrointestinal disorders
‡Includes a subset of Medical Dictionary for Regulatory Activities system organ class of renal and urinary disorders events indicative of intrinsic kidney disease, plus increased/abnormal blood creatinine or renal transplant from other system organ classes
SAEs = Serious adverse events

43. Post Hoc Analysis: Cardiovascular Events Through 1 Year
Aflibercept
(N = 224)
Bevacizumab
(N = 218)
Ranibizumab
Global P-Value unadjusted/
adjusted*
Any Cardiovascular Event,† excluding Hypertension 9%
17%
0.0121
0.0242
Any Cardiovascular Event†
19%
16%
26%
0.0383
0.0814
* Adjusted for potential confounders: gender, age at baseline, Hemoglobin A1c at baseline, diabetes type, diabetes duration at baseline, insulin use, prior coronary artery disease, prior myocardial infarction, prior stroke, prior transient ischemic attack, prior hypertension, smoking status
† Events with a MedDRA system organ class of cardiac disorder or vascular disorder OR considered by the medical monitor as related to a cardiac or vascular event (cardiac murmur, cardiac pacemaker insertion/replacement, coronary arterial stent insertion, heart rate irregular, and stent placement)
Pairwise comparisons (adjusted for multiple comparisons):
A-B: P=1.0, A-R: P=0.015, B-R: P = 0.014
A-B: P=0.68, A-R: P=0.040, B-R: P = 0.024
A-B: P=0.53, A-R: P=0.087, B-R: P = 0.038
A-B: P=0.37, A-R: P=0.19, B-R: P = 0.081
† Includes events with a Medical Dictionary for Regulatory Activities system organ class of cardiac disorder or vascular disorder as coded by the medical monitor. The following additional events not coded under these systems but related to a cardiac or vascular event or intervention are also included in the cardiovascular definition: cardiac murmur, cardiac pacemaker insertion/replacement, coronary arterial stent insertion, heart rate irregular, and stent placement. Participants with multiple events are only included once in the overall tabulation but could be included in more than one of the subcategories.
‡Global (overall 3 group comparison) P-value from Fisher’s Exact Test. Pairwise comparisons from Fisher’s Exact Test (adjusted for multiple comparisons by taking the maximum of the global and pairwise comparison P-values): aflibercept-bevacizumab: P=1.0, aflibercept-ranibizumab: P=0.015, bevacizumab-ranibizumab: P= Global P-value from Poisson model with robust variance estimation using the log link,4 adjusting for gender, age at baseline, Hemoglobin A1c at baseline, diabetes type, diabetes duration at baseline, insulin use, prior coronary artery disease, prior myocardial infarction, prior stroke, prior transient ischemic attack, prior hypertension, smoking status: P= Pairwise comparisons from this model (adjusted for multiple comparisons by taking the maximum of the global and pairwise comparison P-values): bevacizumab-aflibercept: P=0.68, ranibizumab-aflibercept: P=0.040, ranibizumab-bevacizumab: P=0.024.
§Global (overall 3 group comparison) P-value from Fisher’s Exact Test. Pairwise comparisons from Fisher’s Exact Test (adjusted for multiple comparisons by taking the maximum of the global and pairwise comparison P-values): aflibercept-bevacizumab: P=0.53, aflibercept-ranibizumab: P=0.087, bevacizumab-ranibizumab: P= Global P-value from Poisson model with robust variance estimation using the log link,4 adjusting for gender, age at baseline, Hemoglobin A1c at baseline, diabetes type, diabetes duration at baseline, insulin use, prior coronary artery disease, prior myocardial infarction, prior stroke, prior transient ischemic attack, prior hypertension, smoking status: P= Pairwise comparisons from this model (adjusted for multiple comparisons by taking the maximum of the global and pairwise comparison P-values): bevacizumab-aflibercept: P=0.37, ranibizumab-aflibercept: P=0.19, ranibizumab-bevacizumab: P=0.081.

44. Post Hoc Analysis: Cardiovascular Events
Aflibercept
(N = 224)
Bevacizumab
(N = 218)
Ranibizumab
Any Cardiovascular Event
Cardiac Events 6%
11%
Cerebrovascular Events 2% 5%
Peripheral Vascular Disease Events
<1%
Venous Disease Events
Hypertension Events
12% 7%
Other Cardiovascular Events 3%
† Includes events with a Medical Dictionary for Regulatory Activities system organ class of cardiac disorder or vascular disorder as coded by the medical monitor. The following additional events not coded under these systems but related to a cardiac or vascular event or intervention are also included in the cardiovascular definition: cardiac murmur, cardiac pacemaker insertion/replacement, coronary arterial stent insertion, heart rate irregular, and stent placement. Participants with multiple events are only included once in the overall tabulation but could be included in more than one of the subcategories.
‡Global (overall 3 group comparison) P-value from Fisher’s Exact Test. Pairwise comparisons from Fisher’s Exact Test (adjusted for multiple comparisons by taking the maximum of the global and pairwise comparison P-values): aflibercept-bevacizumab: P=1.0, aflibercept-ranibizumab: P=0.015, bevacizumab-ranibizumab: P= Global P-value from Poisson model with robust variance estimation using the log link,4 adjusting for gender, age at baseline, Hemoglobin A1c at baseline, diabetes type, diabetes duration at baseline, insulin use, prior coronary artery disease, prior myocardial infarction, prior stroke, prior transient ischemic attack, prior hypertension, smoking status: P= Pairwise comparisons from this model (adjusted for multiple comparisons by taking the maximum of the global and pairwise comparison P-values): bevacizumab-aflibercept: P=0.68, ranibizumab-aflibercept: P=0.040, ranibizumab-bevacizumab: P=0.024.
§Global (overall 3 group comparison) P-value from Fisher’s Exact Test. Pairwise comparisons from Fisher’s Exact Test (adjusted for multiple comparisons by taking the maximum of the global and pairwise comparison P-values): aflibercept-bevacizumab: P=0.53, aflibercept-ranibizumab: P=0.087, bevacizumab-ranibizumab: P= Global P-value from Poisson model with robust variance estimation using the log link,4 adjusting for gender, age at baseline, Hemoglobin A1c at baseline, diabetes type, diabetes duration at baseline, insulin use, prior coronary artery disease, prior myocardial infarction, prior stroke, prior transient ischemic attack, prior hypertension, smoking status: P= Pairwise comparisons from this model (adjusted for multiple comparisons by taking the maximum of the global and pairwise comparison P-values): bevacizumab-aflibercept: P=0.37, ranibizumab-aflibercept: P=0.19, ranibizumab-bevacizumab: P=0.081.

45. Discussion
All three anti-VEGF agents, on average, produced substantial visual acuity improvement by 1 month, sustained through 1 year.
On average, greater improvement occurred with aflibercept, but relative effect varied by initial visual acuity.
Mild initial vision loss (20/32-20/40, 50% of study eyes): little difference in mean visual acuity at 1 year
Worse initial vision loss: aflibercept had an advantage over the other agents
Statistically significant: Mean improvement of 18.9 for aflibercept vs for bevacizumab (P<0.001) and vs with ranibizumab (P = 0.003)
Clinically meaningful: For example, relative improvement ≥15 letters (>3 Snellen lines) in 63% more aflibercept-treated eyes than bevacizumab-treated eyes, and 34% more than ranibizumab-treated eyes

46. Discussion
Bevacizumab had a lesser effect on reducing macular edema than the other two agents, regardless of starting acuity.
Few eyes in any group had substantial visual acuity loss.
Median number of injections: 9 to 10 in all three groups.
Fewer eyes in the aflibercept group received focal/grid laser for DME after 24 weeks, presumably because a greater % of eyes in the aflibercept group had resolution of central DME (which drives decision to apply laser).

47. Discussion
Serious adverse event, death, and hospitalization rates appeared similar among treatment groups.
Significant differences in frequencies of major cardiovascular events were not identified
However, post-hoc analysis combining MedDRA system organ classes of cardiac and vascular resulted in more participants in the ranibizumab group reporting these adverse events.
This is inconsistent with prior studies and may be due to chance.
Endophthalmitis was rare: 0.02% of injections.
No differences in intraocular inflammation.

48. Discussion Bevacizumab:
Note: a central pharmacy repackaged into single use vials
Testing was completed for sterility, purity, and potency, a standard that may not be available in a clinical practice setting
Results may not apply to eyes with persistent or recurrent DME already receiving anti-VEGF

49. Conclusion
All three anti-VEGF agents are effective treatments for DME causing vision impairment.
When initial visual acuity loss is mild, on average there is little difference in visual acuity at 1-year.
At worse levels of initial visual acuity aflibercept is more effective at improving vision.

50. Thank You on Behalf of Diabetic Retinopathy Clinical Research Network (DRCR.net)
A complete list of all DRCR.net investigator financial disclosures and these slides can be found at
Full protocol available on clinicalTrials.gov (NCT )
Reference: DOI: /NEJMoa
Diabetic Retinopathy Clinical Research Network. Aflibercept, ranibizumab, or bevacizumab for diabetic macular edema. NEJM 2015;372:xxx-xxx. 50