The greatest likelihood of lessening the threat of diabetic retinopathy is through prevention. Preventative strategies must target pathogenic events that occur early in diabetes, and incorporate methods for monitoring outcomes longitudinally and noninvasively. Previous studies suggest that the formation of platelet-fibrin microthrombi could be an early pathogenic event in the closure and obliteration of diabetic retinal capillaries, and do show reduced retinal blood flow in patients with short diabetes duration and no or minimal retinopathy. The hypothesis to be tested in this project is that the reduced retinal blood flow reflects increased vascular resistance due to microthrombosis, and, operationally, that antiplatelet agents normalize the reduced retinal blood flow. The project aims to (1) confirm that, under basal conditions, retinal blood flow measured with the laser Doppler method in a large group of type 1 diabetic patients with no or minimal retinopathy differs from the flow measured in age- and sex-matched nondiabetic control subjects; (2) determine whether the response of retinal blood flow to low-dose aspirin--expected to be mostly or solely antithrombotic--administered for two months versus placebo, differs between the diabetic and the control group; and (3) determine whether the response of retinal blood flow to low-dose aspirin in type 1 diabetic patients differs from the response to another antiplatelet agent, which is highly selective and acts downstream of the site of aspirin action. The study is designed as a two-arm (diabetic patients and controls), parallel-group, double-masked, randomized, placebo-controlled trial, involving individuals 18-40 years of age with diabetes duration of one to ten years and no or minimal retinopathy. The diabetic subjects will be recruited from the Diabetes Center of the Massachusetts General Hospital. The retinal blood flow measurements will be performed with the Canon Laser Blood Flowmeter, an instrument approved by the FDA and usable with ease in the clinical setting. A finding that early reduction of blood flow reflects the occurrence of microthrombosis in the retina of short-term diabetic patients will have identified a pathogenic process for diabetic retinopathy, a surrogate endpoint and a probe for its early detection, and a target for early intervention using benign and clinically available drugs.
| Lorenzi, M; Feke, G T; Cagliero, E et al. (2008) Retinal haemodynamics in individuals with well-controlled type 1 diabetes. Diabetologia 51:361-4 |
