Retinal vascular changes and 20-year incidence of lower extremity amputations in a cohort with diabetes

Objective: To examine the association of retinal vascular changes with the incidence of lower extremity amputations (LEAs) in a cohort with diabetes mellitus. Methods: Baseline examinations were performed in a cohort of 996 persons with diabetes diagnosed before the age of 30 years and using insulin. History of LEA was obtained at baseline and at 4, 10, 14, and 20 years. The cumulative 20-year incidence of first LEA was calculated by the product-limit method in 906 persons with follow-up information. Retinal arterioles and venules were measured on digitized fundus photographs obtained at baseline by a standard protocol. Generalized arteriolar narrowing was defined as the lowest 25% of the arteriole-venule ratio. Measurements were obtained in at least one eye for 820 persons. Focal arteriolar narrowing and arteriovenous nicking were also determined from fundus photographs by a standard protocol. Results: The 20-year cumulative incidence of LEAs was 9.9%. The unadjusted risk of undergoing a LEA was higher in persons with generalized arteriolar narrowing than in those without it (15.7% vs 5.7%; odds ratio [OR], 3.08; 95% confidence interval [CI], 1.60-4.68), and in persons with focal narrowing (33.1% vs 6.8%; OR, 5.59; 95% CL 3.27-9.54). The results for arteriovenous nicking were not significant. With control for age, sex, levels of glycosylated hemoglobin, diastolic blood pressure, and history of ulcers of the feet, the relationships were attenuated but still statistically significant for both generalized narrowing (OR, 1.89; 95% CL 1.06-3.35) and focal narrowing (OR, 3.56-195% CL 1.87-6.78). Conclusion: In persons with diabetes, generalized as well as focal retinal arteriolar narrowing may reflect damage to the microvasculature, which manifests itself elsewhere in the body as a need for LEAs.