1. The Diabetic Retinopathy Clinical Research Network
Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt vs Deferred Laser Treatment:
3-year Randomized Trial Results

2. Background
As previously reported, intravitreal ranibizumab with either prompt or deferred laser was more effective for DME through at least 2 years as compared with prompt laser alone
The study was extended from the planned 3 years to 5 years to provide insight into the long- term course of DME treated with ranibizumab
This report presents comparison data through 3 years for eyes randomized to the two ranibizumab groups 2

3. Completion of 3 Year Visit
Completed: N = 291 (81%)
Not Completed: N = 70 (19%)
Death: N = 26
Withdrawals from the study: N = 27
Lost to follow-up: N = 14
Missed: N = 3
Completion rate (excluding deaths): 87%
Baseline characteristics similar among completers and non-completers 3 3

4. Visits Prior to 3 Years* Ranibizumab + Prompt Laser N=144
+ Deferred Laser
N=147
Median number of visits in year one 13
Median number of visits in year two 8 10
Median number of visits in year three 7
Median number of visits prior to 3 year visit 28 30
* Only eyes that completed 3 year visit

5. Treatment

6. Injections Prior to 3 Year*
Ranibizumab
+ Prompt Laser
N=144
+ Deferred Laser
N=147
Maximal number of injections prior to 3- year visit 39
*Only eyes that completed 3 year visit

7. Injections Prior to 3 Year*
Ranibizumab
+ Prompt Laser
N=144
+ Deferred Laser
N=147
Maximal number of injections prior to 3- year visit 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

8. Injections Prior to 3 Year*
Ranibizumab
+ Prompt Laser
N=144
+ Deferred Laser
N=147
Maximal number of injections prior to 3- year visit 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
*Only eyes that completed 3 year visit

9. Injections Prior to 3 Year*
Ranibizumab
+ Prompt Laser
N=144
+ Deferred Laser
N=147
Maximal number of injections prior to 3- year visit 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
Median number of injections prior to 3 year visit 12 15
*Only eyes that completed 3 year visit

10. Focal/Grid Laser Prior to 3 Years*
Ranibizumab
+ Prompt Laser
N = 144
+ 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
% of eyes that received focal/grid laser treatments from baseline to (prior to) 3-year visit
100%
46%
* Only eyes that completed 3-year visit

11. Visual Acuity

12. Mean Change in Visual Acuity* at Follow-up Visits
N = 338 (52 weeks)
N = 317 (104 weeks)
N = 291 (156 weeks)
*Truncated to ± 30 letters

13. Change in Visual Acuity*
Change in Visual Acuity (letters)**
Ranibizumab +
Prompt
Laser
N = 144
Deferred
N = 147
Estimated Difference (B vs. C) (95% CI)
[P-Value]
2-years (Estimated Means)
+7.2
+9.0
-1.8 (-3.6 to +0.1)
[P = 0.06]
3- Years (Estimated Means)
+6.8
+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

14. Visual Acuity Gain at 3 Years
Proportion of Visual Acuity Change
Ranibizumab + Prompt Laser
N = 144
Ranibizumab + Deferred Laser
N = 147

15. Visual Acuity Subgroup Analyses

16. Change in Visual Acuity at 3 Year Stratified by Baseline Visual Acuity

17. Retinal Thickening

18. Mean Change in CSF Thickening at Follow-up Visits
N = 334 (52 weeks)
N = 305 (104 weeks)
N = 259 (156 weeks)

19. Conclusions
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 1-year to 3-year visit.