1. ACCORD Eye Study Results
Emily Y. Chew, MD
National Eye Institute/National Institutes of Health
Bethesda, MD
For the ACCORD Study and ACCORD Eye Study Research Groups

2. ACCORD Eye Study Trial Goal
To determine whether:
Intensive glycemic control
Combination therapy of dyslipidemia with fenofibrate and simvastatin
Intensive blood pressure control
Affect the progression of diabetic retinopathy in a subset of ACCORD Participants

3. ACCORD Eye Study Design
Baseline and Year 4 comprehensive
eye exams including:
Visual acuity measurements
Fundus photography of 7 standard stereoscopic fields
Central grading of the fundus photographs using the Early Treatment Diabetic Retinopathy Study (ETDRS) Classification of diabetic retinopathy

4. Fundus Photo: 7 stereo fields

5. ACCORD Eye Study Design
Progression of diabetic retinopathy assessed in the ACCORD Eye Study is the primary microvascular endpoint for the ACCORD Study
Inclusion: all ACCORD main trial participants are eligible (beginning February 2003)
Exclusion: Previous laser photocoagulation, vitrectomy, or inability to progress 3 steps on the ETDRS Scale of diabetic retinopathy severity.

6. ACCORD Eye Study Design
Primary Outcome is progression of retinopathy:
Combined outcome of progression of diabetic retinopathy of at least 3 levels on the ETDRS scale (person scale) assessed on fundus photographs at 4 years compared with baseline; photocoagulation; or vitrectomy during follow-up.

7. Power/Sample Size Power Assumptions
88% power for Glycemia (15% effect)
91% power for Lipid (20% effect)
80% power for Blood pressure (20% effect)
Assumptions
38.4% 4-year progression in control group
N=3211 with baseline and follow-up
Expected 79% retention, target was 4065
10% death
10% refusal at follow-up
1% lack of dilation

8. Recruitment and Retention
3537 at baseline (87.0% of goal)
65 had laser photocoagulation or vitrectomy prior to baseline
3472 recruited and eligible for study
113 (3.3%) died prior to follow-up window opening
503 (14.5%) missed visits or technical problems
2856 (82.3%) had both baseline and follow-up visits

9. Participant Demographics
Variable
ACCORD Eye with Follow-up
ACCORD Eye without
Follow-up
Rest of ACCORD Main Trial N
2856
616
5605
Age (yr)
61.6 (6.3)
62.7 (7.1)
62.3 (6.9)
Diabetes Duration (yr)
10.0 (7.1)
10.3 (7.0)
11.2 (8.1)
Female
38.2%
39.5%
38.4%
Previous
CVD
31.3%
37.0%
37.1%
Nonwhite
30.1%
35.4%
37.3%

10. Participant Serum Factors
Variable
ACCORD Eye with Follow-up
ACCORD Eye without
Follow-up
Rest of ACCORD Main Trial
HbA1c (%)
8.2 (1.0)
8.4 (1.1)
HDL (mg/dL)
41.9 (11.3)
41.7 (10.9)
41.8 (11.7)
LDL (mg/dL)
100.7 (32.7)
105.3 (35.0)
105.0 (34.3)
Triglycerides (mg/dL)
195.1 (162.6)
198.2 (144.2)
189.6 (148.7)

11. Participant Demographics
Variable
ACCORD Eye with Follow-up
ACCORD Eye without
Follow-up
Rest of ACCORD Main Trial
Systolic BP
134.5 (17.0)
136.4 (17.2)
136.5 (17.1)
Diastolic BP
74.9 (10.5)
75.3 (11.3)
74.7 (10.7)
Body Mass Index
32.4 (5.5)
32.7 (5.5)
32.2 (5.5)
Visual Acuity
Snellen visual acuity
75.9 (10.2)
(20/25)
73.7 (10.9)
(20/30)
72.8 (12.7)
Smoking Never
41.6%
36.9%
42.0%
Former
44.8%
47.9%
43.4%
Current
13.6%
15.3%
14.6%

12. Proportions Missing
616 Missing follow-up from 3472 with Baseline Visits
Blood Pressure Trial
Lipid Trial
Glycemia
Intensive
Standard
Fenofibrate + Statin
Placebo + Statin
TOTALS
19%
14%
18%
17%
16%

13. ACCORD Eye Study Results
253 (8.9%) participants had progression:
3 level worsening of diabetic retinopathy on the ETDRS scale (using the Person Scale)
Laser photocoagulation
Vitrectomy for diabetic retinopathy

14. Proportion of Participants with Diabetic Retinopathy Progression at 4 years
Blood Pressure
Lipid
N=2856
Total
Glycemia
Intensive
Standard
Fenofibrate
& Simvastatin
Placebo
TOTALS
9.2% (29/315)
8.1% (25/308)
5.3%
(21/400)
7.1% (29/406)
7.5% (104/1429)
11.4%
(38/332)
9.4%
(29/308)
7.6% (31/406)
13.4% (51/381)
10.4% (149/1427)
10.4%
(67/647)
8.8% (54/616)
6.5% (52/806)
10.2% (80/787)
8.9%
(253/2856)

15. Primary Analysis Effect Odds Ratio 95% CI P-value Glycemia 0.67
(0.51,0.87)
0.0025

16. Primary Analysis Effect Odds Ratio 95% CI P-value Glycemia 0.67
(0.51,0.87)
0.0025
Lipid
0.60
(0.42,0.86)
0.0056

17. Primary Analysis Effect Odds Ratio 95% CI P-value Glycemia 0.67
(0.51,0.87)
0.0025
Lipid
0.60
(0.42,0.86)
0.0056 BP
1.23
(0.84,1.79)
0.29

18. ACCORD Eye Study Results
Subgroup Analyses
NO statistically significant interactions for any of the prespecified subgroups

19. ACCORD Eye Study Conclusions
Intensive glycemia and combination of fenofibrate and simvastatin reduced the proportion whose retinopathy progressed by about one-third
Effects were consistent across subgroups
No statistically significant effect of intensive blood pressure
No subgroup with effect

20. ACCORD Research Groups
Thank YOU!!
ACCORD Research Groups
& ACCORD Participants