Elsevier

Ophthalmology

Volume 121, Issue 12, December 2014, Pages 2443-2451
Ophthalmology

Original article
The Effects of Medical Management on the Progression of Diabetic Retinopathy in Persons with Type 2 Diabetes: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study

https://doi.org/10.1016/j.ophtha.2014.07.019Get rights and content

Purpose

To report additional ocular outcomes of intensive treatment of hyperglycemia, blood pressure, and dyslipidemia in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.

Design

Double 2×2 factorial, multicenter, randomized clinical trials in people with type 2 diabetes who had cardiovascular disease or cardiovascular risk factors. In the glycemia trial, targets of intensive and standard treatment were: hemoglobin A1c <6.0% and 7.0% to 7.9%, respectively, and in the blood pressure trial: systolic blood pressures of <120 and <140 mmHg, respectively. The dyslipidemia trial compared fenofibrate plus simvastatin with placebo plus simvastatin.

Participants

Of the 3472 ACCORD Eye Study participants enrolled, 2856 had 4-year data (85% of survivors).

Methods

Eye examinations and fundus photographs were taken at baseline and year 4. Photographs were graded centrally for retinopathy severity and macular edema using the Early Treatment Diabetic Retinopathy Study (ETDRS) methods.

Main Outcome Measures

Three or more steps of progression on the ETDRS person scale or treatment of retinopathy with photocoagulation or vitrectomy.

Results

As previously reported, there were significant reductions in the primary outcome in the glycemia and dyslipidemia trials, but no significant effect in the blood pressure trial. Results were similar for retinopathy progression by 1, 2, and 4 or more steps on the person scale and for ≥2 steps on the eye scale. In the subgroup of patients with mild retinopathy at baseline, effect estimates were large (odds ratios, ∼0.30; P < 0.001), but did not reach nominal significance for participants with no retinopathy or for those with moderate to severe retinopathy at baseline.

Conclusions

Slowing of progression of retinopathy by intensive treatment of glycemia was observed in ACCORD participants, whose average age and diabetes duration were 62 and 10 years, respectively, and who had cardiovascular disease or cardiovascular risk factors. The effect seemed stronger in patients with mild retinopathy. Similar slowing of progression was observed in patients treated with fenofibrate, with no effect observed with intensive blood pressure treatment. This is the second study to confirm the benefits of fenofibrate in reducing diabetic retinopathy progression, and fenofibrate should be considered for treatment of diabetic retinopathy.

Section snippets

The ACCORD Study

The designs of the ACCORD study and the ACCORD Eye Study have been described elsewhere.1, 6 The ACCORD study was approved by the institutional review board of each clinical center. Briefly, the ACCORD study was a multicenter study with a total of 10 251 participants randomly assigned in equal numbers to 2 glycemia management treatment arms. The intensive treatment arm aimed to achieve and maintain glycated hemoglobin (HbA1c) level <6.0%. The standard treatment arm targeted an HbA1c range of

Results

From January 2001 to October 2005, 10 251 participants were recruited in the main ACCORD trial. From October 2003 to February 2006, 3472 eligible participants were enrolled in the ACCORD Eye Study. Of these, 2856 (85% of survivors) returned for the second eye examination and fundus photographs.

Discussion

The previously reported findings of reductions in diabetic retinopathy progression resulting from the intensive treatment of hyperglycemia and dyslipidemia studied in ACCORD7 are confirmed by the analyses reported and extended by analyses of subgroups and of alternative outcome measures. In both trials, 4-year rates of the primary outcome, a composite of ≥3 steps of progression along the ETDRS diabetic retinopathy severity scale for persons or treatment of diabetic retinopathy with

References (23)

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    Supplemental material is available at www.aaojournal.org.

    Financial Disclosure(s): The author(s) have made the following disclosure(s): R.P.D.: Board member – EyeKor, LLC; Consultant – Allergan, GlaxoSmithKline, Thrombogenics (Data and Safety Monitoring Board [DSMB]), Oraya, Eli Lilly. L.H.P.: Grants – National Heart, Lung, and Blood Institute, NIH. D.C.G.: Consultant to and receives payment for lectures, Speakers bureaus – Merck; DSMB – Takeda. L.A.L,: Consultant – AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novo Nordisk, Roche, Sanofi, Servier, Takeda; Research grants – AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novo Nordisk, Roche, and Sanofi; Speakers bureaus – AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Takeda. C.G.: Consultant – Thrombogenics. W.T.A.: Consultant – NIH/Office of Behavioral and Social Sciences Research and several DSMBs; Receives payment for the development of educational presentations, has a salary covered by NIH grants; Employed –Wake Forest School of Medicine. F.I.-.B.: Research grant – Novo-Nordisk for Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER), and Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN); Shares –Thermalin Diabetes.

    Supported by contracts (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute and the National Institutes of Health (NIH), with additional support from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Eye Institute, the National Institute on Aging, and the Centers for Disease Control and Prevention. General clinical research centers provided support at many sites. The following companies donated study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, Sanofi-Aventis U.S., and Takeda Pharmaceuticals.

    The study was registered with ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye Study.

    See Editorial on page 2295.

    A listing of the Action to Control Cardiovascular Risk in Diabetes Eye Study Research Group is shown in the Supplementary Appendix.

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