The Diabetic Retinopathy
Clinical Research Network
Effects of Intravitreal Ranibizumab or
Triamcinolone on Diabetic Retinopathy
Jennifer K. Sun, MD, MPH
Sponsored by the National Eye Institute,
National Institutes of Health, U.S. Department of Health and Human
Services
1
DRCR.net Protocol B: Laser vs.
Intravitreal Triamcinolone for DME
 840 eyes (693 subjects)
• Laser group: N = 330
• 1 mg IVT group: N = 256
• 4 mg IVT group: N = 254
 Major Eligibility Criteria:
• VA 20/40 to 20/320
• CSF >= 250 microns on OCT
 Visits (and retreatment assessment) every 4
months through 3 years
 Primary Outcome: VA at 2 years
2
Outcome Definition
Progression of retinopathy up to 3 years
(any of the following):
• Progressed from NPDR at baseline to PDR
during follow-up*
• Received PRP between baseline and followup
• Reported a vitreous hemorrhage between
baseline and follow-up
• Worsened 2 or more levels on the ETDRS
diabetic retinopathy scale*
*Based on Reading Center grading of annual fundus photos
3
Cumulative Probability* of
Progression of Retinopathy
Cumulative Probability
40%
30%
37%
35%
Laser
1mg
4mg
31%
29%
30%
21%
19%
21%
20%
14%
10%
0%
Months
0
4
8
12 16
20
*calculated using the life-table method
24
28
32
36
Note: 14% were censored prior to 2 yr visit and an additional 34% between the 2 and 3 yr visits (of
which only 7% had the potential to complete the 3 yr visit due to early closeout of the study)
4
Treatment Group Comparisons
at 1, 2, and 3 Years
1 Year
2 Years
3 Years
Comparison
P value*
Laser v 1 mg
0.71
Laser v 4 mg
0.03
1 mg v 4 mg
0.08
Laser v 1 mg
0.64
Laser v 4 mg
0.005
1 mg v 4 mg
0.03
Laser v 1 mg
0.73
Laser v 4 mg
0.02
1 mg v 4 mg
0.07
*From a proportional hazards model adjusting for baseline VA, history of prior
macular photocoagulation, and baseline retinopathy severity
5
Cumulative Probability* of
Progression of Retinopathy
up to 2 Years
Additional Probability
(not counted in prior row)
Laser
N=330
1mg
N=256
4mg
N=254
NPDR to PDR
15%
11%
8%
PRP
9%
6%
5%
Vitreous hemorrhage
6%
9%
5%
Worsened 2 levels
1%
3%
3%
Combined definition
31%
29%
21%
*calculated using the life-table method
6
Cumulative Probability* of
Progression of Retinopathy
up to 2 Years
Total Probability
for Each Criteria
Laser
N=330
1mg
N=256
4mg
N=254
NPDR to PDR
15%
11%
8%
PRP
14%
10%
9%
Vitreous hemorrhage
16%
16%
11%
Worsened 2 levels
15%
11%
11%
Combined definition
31%
29%
21%
*calculated using the life-table method
7
Cumulative Probability* of
Progression of Retinopathy
up to 3 Years
Additional Probability
(not counted in prior row)
Laser
N=330
1mg
N=256
4mg
N=254
NPDR to PDR
19%
14%
16%
PRP
10%
7%
6%
Vitreous hemorrhage
6%
12%
5%
Worsened 2 levels
2%
2%
3%
Combined definition
37%
35%
30%
*calculated using the life-table method
8
Cumulative Probability* of
Progression of Retinopathy
up to 3 Years
Total Probability
for Each Criteria
Laser
N=330
1mg
N=256
4mg
N=254
NPDR to PDR
19%
14%
16%
PRP
18%
11%
12%
Vitreous hemorrhage
19%
20%
15%
Worsened 2 levels
17%
15%
17%
Combined definition
37%
35%
30%
*calculated using the life-table method
9
Conclusions
 As compared with laser, 4 mg IVT may reduce
the risk of progression of retinopathy at 1, 2,
and 3 years
 Difference cannot be explained by an increase
in retinopathy caused by focal/grid laser
• Similar risk in laser group and 1 mg IVT group
• Similar risk of development of PDR in ETDRS
immediate laser group (11.1%) and deferred laser
group (10.8%)
 Use of IVT to reduce risk of progression of
retinopathy is not warranted at this time
• IVT is associated with cataract and elevated IOP
• PDR can be treated relatively safely with PRP
10
DRCR.net Protocol I: Ranibizumab+
Prompt or Deferred Laser or
Tiamcinolone + Prompt Laser for DME
 854 eyes (691 subjects)
•
•
•
•
Sham + Prompt Laser: N = 293
Ranibizumab + Prompt Laser: N = 187
Ranibizumab + Deferred Laser: N = 188
Triamcinolone + Prompt Laser: N = 186
 Major Eligibility Criteria:
• VA ~ 20/32 to 20/320
• Definite retinal thickening due to DME involving the
center of the macula
• CSF ≥ 250 microns on OCT
11
Progression/Regression in Diabetic
Retinopathy at 1 Year by Baseline Severity
Sham
+Prompt
Laser
Ranibizumab
+Prompt
Laser or
Deferred
Laser
Triamcinolone
+Prompt
Laser
N = 150
N = 182
N = 80
Improved by ≥2 levels
4%
25%
25%
Worsened by ≥2 levels
7%
3%
3%
P = 0.08
P =0.17
Change from baseline to
1-year visit*
Baseline Severity: Moderately
Severe NPDR or Better
P value for comparison with
Sham
*Photos were missing or ungradeable for 61 eyes in the sham+prompt laser group, 72 eyes in the ranibizumab
groups, and 33 eyes in the triamcinolone+prompt laser group
12
Progression/Regression in Diabetic
Retinopathy at 1 Year by Baseline Severity
Sham
+Prompt
Laser
Ranibizumab
+Prompt
Laser or
Deferred
Laser
Triamcinolone
+Prompt
Laser
N = 83
N = 121
N = 70
Improved by ≥2 levels
19%
28%
13%
Worsened by ≥2 levels
8%
1%
3%
P = 0.03
P = 0.17
Change from baseline to
1-year visit*
Baseline Severity: Severe
NPDR or worse
P value for comparison with
Sham
*Photos were missing or ungradeable for 61 eyes in the sham+prompt laser group, 72 eyes in the ranibizumab
groups, and 33 eyes in the triamcinolone+prompt laser group
13
Retinopathy Progression During 1
Year of Follow-up
Reported vitreous
hemorrhage OR
received PRP
P Value for
comparison with
sham
Sham
N = 293
Ranibizumab
N = 375
Triamcinolone
N = 186
8%
3%
3%
--
0.002
0.02
14
Conclusions
 During the first year, eyes assigned to
Ranibizumab groups or Triamcinolone group
compared with Laser group were:
• More likely to show retinopathy regression
• Less likely to show retinopathy progression
• Less likely to have a VH or receive PRP
Limitations of this study include large numbers
of missing or ungradable photos
Future investigations are needed to definitively
demonstrate effect of anti-VEGF therapy or
steroid on retinopathy severity
15