1. The Diabetic Retinopathy Clinical Research Network What is the Role of Laser In Treating Diabetic Macular Edema in the Era of Anti-VEGF Therapy? 1

2.  None 2 Financial Disclosures

3. 3 7-6-11

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6. 6 12-7-11 After 3 Anti-VEGF injections

7. 7 2-29-12 After 6 Anti-VEGF injections

8.   What should be done next?   Is Laser the next step?   Does it help? 8

9. Response to Laser in the ETDRS 9

10. ETDRS Data*: Change in VA from Baseline 10 *Of eyes with CI-DME at baseline

11.  Anti-VEGF therapy is now the gold standard for treating diabetic macular edema in eyes with impaired vision. Focal laser is now used for eyes not responding well to Anti-VEGF or eyes where Anti-VEGF is contraindicated. Some doctors use it as the primary treatment in eyes with very focal disease such as a circinate ring. 11

12. DRCR.net Protocol I Data (Ranibizumab+prompt laser & Ranibizumab+deferred laser groups) 12

13. Visual Acuity 13

14. Mean Change in Visual Acuity * at Follow-up Visits 14 *Truncated to ± 30 letters N = 338 (52 weeks) N = 317 (104 weeks) N = 291 (156 weeks)

15. 15 Change in Visual Acuity* Change in Visual Acuity (letters)** Ranibizumab + Prompt Laser N = 144 Ranibizumab + Deferred Laser 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

16. Retinal Thickening 16

17. Mean Change in CSF Thickening at Follow-up Visits 17 N = 334 (52 weeks) N = 305 (104 weeks) N = 259 (156 weeks)

18. 18 Change in Retinal Thickening at 3 Years* Change in OCT CSF Ranibizumab + Prompt Laser N = 136 Ranibizumab + Deferred Laser N = 132 Median change from baseline (µm) -142-155 Mean change from baseline (µm) -152-174 Thickness <250 µm with at least a 25 µm decrease from baseline 61%63% *Visits occurring between 980 and 1204 days from randomization were included as 3 year visits

19. 19 Focal/Grid Laser Prior to 3 Years * Ranibizumab + Prompt Laser N = 144 Ranibizumab + Deferred Laser N = 147 Maximal possible number of focal/grid laser treatments prior to 3-year visit 1210 Median number of focal/grid laser treatments from baseline to (prior to) 3- year visit 30 % 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

20. DRCR.net New Protocol 20

21. Study Objectives  To compare the efficacy and safety of 1.Anti-VEGF with no laser 2.Anti-VEGF with deferred laser in eyes with DME. 21 Efficacy will be assessed by change in visual acuity at 1 year. The study will be 2 years in duration. Protocol T Treatment Algorithm