1. Sponsored by the National Eye Institute,
A Randomized Trial Comparing Intravitreal Triamcinolone to Focal/Grid Photocoagulation for Diabetic Macular Edema
Sponsored by the National Eye Institute,
National Institutes of Health, U.S. Department of Health and Human Services.

2. Intravitreal Triamcinolone for DME
: potential benefit first reported1,2
Short term improvement in visual acuity
Rapid decrease in retinal thickening on OCT
2005: 91% of retina specialists surveyed (N=371) would use IVT for persistent DME3
Community equipoise present: Randomized, controlled comparison with standard care (focal/grid photocoagulation) needed
1- Jonas JB, et al. Am J Ophthalmol 2001;132:425-7
2- Martidis A, et al. Ophthalmology 2002;109:920-7
3- American Society of Retina Specialists Preferences and Trends Survey 2005

3. DRCR.net Study Design Multicenter, randomized clinical trial
Three treatment groups
Focal/grid laser
1 mg IVT
4 mg IVT
Duration of follow-up: 3 years
Follow-up visits and re-treatment as often as every 4 months

4. Primary Study Objective
To compare the efficacy and safety of preservative-free IVT (1 mg or 4 mg) with focal/grid laser

5. Efficacy Outcomes Primary outcome assessment at 2 years
Primary outcome measure: visual acuity
Scientific objective: mean change in VA
Regulatory objective for FDA: proportion with decrease in VA letter score >15
Secondary measure: Retinal thickening on OCT

6. Major Eligibility Criteria
At least 18 years old
Type 1 or type 2 diabetes
Center-involved DME confirmed on OCT
(central subfield thickness >250 microns)
Best-corrected VA letter score 73 to 24
(Snellen equivalent 20/40 to 20/320)

7. Results

8. Study Enrollment and Completion
840 eyes (693 subjects) enrolled at 88 clinical sites ( )
Treatment Groups
Laser: N = 330
1 mg: N = 256
4 mg: N = 254
2-year visit completion rate
88% excluding deaths

9. Primary Outcome: Mean Change in Visual Acuity at 2 Years
Mean Change in VA (letter score)
Laser
N=330
1 mg
N=256
4 mg
N=254 +1 -2 -3
Pairwise Comparisons
Mean Difference*
P value*
Laser vs. 1 mg
+3.5 letters
0.02
Laser vs. 4 mg
+4.6 letters
0.002
1 mg vs. 4 mg
+1.1 letters
0.49
* Adjusted for baseline VA and prior focal/grid laser

10. Median Visual Acuity in Laser and IVT Treated Eyes
20/32 -
20/40 -
# +
* #
* #
Visual
Acuity
Score
20/50 - *
20/63 -
20/80 -
P < 0.005
* Laser vs. 1mg
# Laser vs. 4mg
+ 1mg vs. 4mg
Months 10 10

11. % Increased >10 Letters in Laser and IVT Treated Eyes
Months 11 11

12. Visual Acuity at 2 Years According to Lens Status
Mean Change in VA (letter score)
Laser
1 mg
4 mg
Pseudophakic at 2 Yrs or Minimal or No Cataract at 2 Yrs
N=178
N=136
N=159 +3
Pseudophakic at Baseline
N=54
N=48
N=43 +2 -1
Includes only subjects with a 2 year visit

13. Mean Visual Acuity Over 3 Years in All Eyes
20/32
20/40
Visual
Acuity
Score
20/50
20/63
20/80 4 8 12 16 20 24 28 32 36
Months 13 13

14. OCT Central Subfield (CSF) Thickening at 2 Years
Change in OCT CSF
Laser
N=220
1 mg
N=178
4 mg
N=162
Mean*
-139
-86
-77
Thickening Decreased >50%
67%
46%
48%
Thickness <250 microns
53%
34%
38%
*Pairwise Comparisons
P value
Laser v 1 mg
<0.001
Laser v 4 mg
1 mg v 4 mg
0.91

15. Median OCT Central Subfield Thickness in Laser and IVT Treated Eyes
(microns)
Months 15 15

16. Change in CSF from 2 Years to 3 Years*
2 year CSF >=250
Laser
N=50
1mg
N=59
4mg
N=54
Mean change (microns)
-79
-44
-84
<250 microns at 3 years
36%
31%
39%
Decreased >=20% and >=50 microns
54%
34%
46%
Increased >=20% and >=50 microns
10%
12%
13%
* Among completers of both the 2 year and 3 year visit 16 16

17. Major Ocular Adverse Events During 2 Years of Follow-up
Laser
N=330
1 mg
N=256
4 mg
N=254
Endophthalmitis*
Pseudoendophthalmitis
Retinal detachment† 2 3
Retinal vein occlusion† 1
Retinal artery occlusion†
Glaucoma procedure 4
Vitrectomy‡ 31 26 19
* 1 case of endophthalmitis occurred after vitrectomy, not related to study drug injection
† Judged not necessarily related to treatment
‡ Includes vitrectomy for diabetic macular edema, vitreous hemorrhage or other cause

18. Intraocular Pressure During 3 Years of Follow-up*
Laser
N=115
1 mg
N=93
4 mg
N=98
Increase >10 mmHg any time 3%
17%
31%
Mean IOP at 3 yr visit (mmHg) 16 17
IOP >21 mmHg at 3 yr visit 5%
15%
10%
On IOP-lowering meds at 3 yr visit 8%
12%
30%
* Among completers of the 3 year visit 18 18

19. Cataract Surgery Prior to 2 Years
Laser
1 mg
4 mg
Phakic at Baseline
N=262
N=203
N=197
Cataract Surgery
13%
23%
51%

20. Cumulative Probability of Cataract Surgery* Over 3 Years
83%
46%
31% 4 8 12 16 20 24 28 32 36
Months
* Among phakic eyes at baseline 20 20

21. Conclusion
VA benefit in 4 mg IVT group at 4 months consistent with published case series
However, no difference in VA between IVT groups and laser group by 1 year
By 2 years, there was a greater VA benefit and fewer side effects (IOP and cataract) in laser group compared with the IVT groups
3 year results similar to the 2 year results
OCT results mirrored VA results

22. Conclusion Results re-affirm importance of laser in management of DME
Focal/grid currently most effective treatment for patients with DME (with characteristics similar to those enrolled in this trial)
Focal/grid currently benchmark against which other new treatments for DME should be compared in clinical trials for DME