There is level 1 evidence for intensive glycemic control for reducing the progression of diabetic retinopathy in persons with type 2 diabetes.

Abstract

Researchers of several medical departments of an academic institution conducted the meta-analysis of studies that evaluated the role of glycemic control in diabetic ocular complications that appears in the current issue of this journal (e-published in October 2014) [1]. Their final conclusion was that more clinical trials are needed to conclusively evaluate the role of glycemic control in ocular complications particularly in persons with type 2 diabetes. I respectfully disagree and counter their argument with discussion regarding study design and the use of surrogate outcomes in studies of diabetic retinopathy; and offer other interpretation of the previous studies. Clinical trial results provide important guidance for care and may not answer all clinical questions posed but there is sufficient level 1 evidence to recommend intensive glycemic control now for persons with type 2 diabetes for the most common and important ocular complications, progression of diabetic retinopathy. I agree with the authors that without a doubt, functional outcomes are most important for the patients. Patients are the ones who suffer from vision loss, reducing their ability to read, drive, and perform other activities of daily living. It is important to point out that prior to the common use of lasers, 50 % of all patients who developed proliferative diabetic retinopathy, the most severe form of diabetic retinopathy, would be legally blind in 5 years [2, 3]. Ophthalmologists practicing before the 1970s described their eye clinics being filled with persons suffering from diabetes who were often accompanied by their seeing-eye dogs. With the onset of laser photocoagulation and the results of the original Diabetic Retinopathy Study [4], this rate of severe vision was reduced initially by 50 % but with further refinement of the laser treatment strategies in the Early Treatment Diabetic Retinopathy Study (ETDRS) [5], the rate of severe vision loss was reduced by 95 % [6], changing this scenario dramatically. This is a highly successful therapy for eradicating severe vision loss in persons with diabetic retinopathy. The studies, which were conducted following the success of the laser photocoagulation, considered visual acuity changes to be secondary outcomes. Even in the highly successful Diabetes Control and Complications Trial (DCCT) [7], visual acuity change was NOT a primary outcome. It was the progression of diabetic retinopathy, along the ETDRS scale [8] which is a classification of diabetic retinopathy severity, a well characterized and highly validated scale for the measurement of diabetic retinopathy. The Food and Drug Administration (FDA) in the United States has accepted the progression along the ETDRS scale as a surrogate outcome for all clinical trials of diabetic retinopathy. A surrogate outcome is an outcome that specific treatment may affect. This surrogate outcome may correlate with a real clinical endpoint, including vision loss in this case. Progression along the scale is a sign of deterioration and eventually, patients develop vision loss from the diabetic retinopathy and may need laser photocoagulation or vitrectomy. A combined outcome of progression along the ETDRS scale and the treatment with laser photocoagulation or vitrectomy is also another outcome used in the clinical trials. If we were to calculate the sample sizes required to reduce the rate of vision loss, it may take tens of thousands of participants in each arm to find a beneficial (or adverse) E. Y. Chew (&) Division of Epidemiology and Clinical Applications, National Eye Institute/National Institutes of Health, Building 10, CRC, Room 3-2531, 10 Center Drive, MSC-1204, Bethesda, MD 20892-1204, USA e-mail: echew@nei.nih.gov