From Pages to Practice

By Rebecca Berger, M.D.

Published April 19, 2017

Ms. Rodwell is a 37-year-old woman who has had type 1 diabetes since the age of 14; she comes to a routine visit to discuss diabetes management. Her last hemoglobin A1c was 7.0%. She has had annual ophthalmologic examinations to evaluate for retinopathy since age 18; her last five examinations have shown mild non-proliferative diabetic retinopathy. Ms. Rodwell has two young children and a full-time job. Each medical appointment is a burden on her time. She asks for your advice: Does she need to continue annual eye exams?

Screening allows early detection of proliferative diabetic retinopathy or clinically significant macular edema; a diagnosis of either of these necessitates treatment to preserve vision. The American Diabetes Association (ADA) recommends that patients with type 1 diabetes receive an initial screening examination for diabetic retinopathy 3 to 5 years after the diabetes diagnosis, followed by every 2 years if no evidence of retinopathy, “at least annually” if any evidence of diabetic retinopathy, and with increasing frequency if retinopathy is progressing. These guidelines provide guidance in a “one-size-fits-all” model.

In this week’s issue of NEJM, researchers aimed to create a practical, evidence-based schedule for diabetic retinopathy screening that could be tailored to individual patients. The investigators analyzed retinal photography data from nearly 24,000 retinopathy examinations over 30 years (in 1441 patients from the Diabetes Control and Complications Trial (DCCT) and 1375 patients from the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study). Diabetic retinopathy was graded from state 1 (no retinopathy) to state 5 (proliferative diabetic retinopathy or clinically significant macular edema). Using cumulative incidence functions, they estimated probabilities of progression associated with increasing screening intervals and proposed the following screening schedule: state 1 (no diabetic retinopathy) — screen every 4 years; state 2 (mild non-proliferative diabetic retinopathy) — screen every 3 years; state 3 (moderate non-proliferative diabetic retinopathy) — screen every 6 months; and state 4 (severe non-proliferative diabetic retinopathy) — screen every 3 months. The goal of the schedule was to limit the rate of progression to state 5 retinopathy between examinations to 5%.

The authors refined the screening schedule by incorporating hemoglobin A1c data. Each 1 percentage-point increase in mean A1c level was associated with a 15.4% higher risk of progression from state 1 to state 2 (hazard ratio; 1.15). Accordingly, a patient with a mean A1c of 6% could wait longer intervals between screenings than the schedule described above, but a patient with an A1c of 10% would require shorter intervals between screenings.

The investigators conclude that their model allows for personalized schedules based on only two factors — degree of retinopathy at baseline and hemoglobin A1c — creating a potentially practical tool for patients and physicians, while minimizing the length of time that severe, potentially vision-threatening retinopathy would remain undetected. In an accompanying editorial, Dr. Jamie Rosenberg from Montefiore Medical Center and Dr. Irena Tsui from UCLA caution, “in a real world population, reminders to schedule and track the performance of an eye examination would typically come from primary care physicians or endocrinologists, whose low rate of referral may decrease further with this more complicated system.”

Results from this study suggest that Ms. Rodwell might be able to extend the interval before her next eye exam to up to 4 years with little or no risk of progression to proliferative diabetic retinopathy, but for now you advise her to follow the ADA guidelines and continue annual eye exams.

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Rebecca is a 2016-2017 NEJM Editorial Fellow and a hospitalist at Massachusetts General Hospital. She graduated from Columbia University College of Physicians and Surgeons in 2013 and completed internal medicine residency at Massachusetts General Hospital in 2016. Her interests include medical education, quality improvement, patient safety, health care delivery innovation, and teaching value in health care.