Original Article Retinal Hemodynamics in Early Diabetic Macular Edema Kit Guan, 1 Chris Hudson, 1,2 Tien Wong, 1 Mila Kisilevsky, 1 Ravi K. Nrusimhadevara, 1 Wai Ching Lam, 1 Mark Mandelcorn, 1 Robert G. Devenyi, 1 and John G. Flanagan 1,2 The objective of this study was to establish the baseline retinal hemodynamic characteristics of stratified groups of diabetic patients at increasing risk for the development of diabetic macular edema (DME). Group 1 had 50 control subjects, group 2 had 56 diabetic patients without clinically visible retinopathy, group 3 had 54 diabetic patients with microaneurysms and/or hard exudates within two disc di- ameters of the fovea in the absence of clinically manifest DME, and group 4 had 40 patients with clinically manifest DME. Retinal hemodynamics (diameter, velocity, maxi- mum-to-minimum velocity ratio, and flow) were assessed. Intraocular pressure, blood pressure, and relevant sys- temic markers of diabetes control and complications were also undertaken. The maximum-to-minimum velocity ratio was elevated with increasing risk of clinically significant DME (P < 0.0001). No significant differences were found between the groups with respect to diameter, velocity, or flow. The maximum-to-minimum velocity ratio was corre- lated to age, duration of diabetes, blood pressure, pulse rate, intraocular pressure, and serum potassium levels. In conclusion, the maximum-to-minimum velocity ratio was significantly increased with increasing risk of development of DME. Retinal arteriolar hemodynamics were positively correlated to age, duration of diabetes, and blood pressure. These findings suggest a reduction in the compliance (i.e., an increase of vascular rigidity) of the arteriolar circula- tion with increasing risk of DME. Diabetes 55:813– 818, 2006 D iabetic retinopathy is a leading cause of visual impairment in the world, including North Amer- ica (1). Due to the increasing prevalence of diabetes, the financial, societal, and personal burden of diabetic retinopathy is increasing dramatically despite improvements in patient education and glycemic control (2– 4). Diabetic retinopathy results from microvas- cular decompensation beginning with basement mem- brane thickening (5) and eventually leading to vascular occlusion and neovascularization (6). Diabetic macular edema (DME) can occur at virtually any stage during diabetic retinopathy development, and it represents the leading cause of visual impairment in people with diabetes (7). Laser photocoagulation is the established treatment for clinically significant DME (8). Although laser photoco- agulation is effective in arresting visual acuity loss due to DME, it is also destructive (9,10). The prevention of the retinal complications of diabetes is becoming increasingly important from a public health standpoint. There is a clear need for improved diagnostic and therapeutic techniques in the management of diabetic retinopathy (11,12). Disturbance of retinal hemodynamics is an accepted surrogate marker of early diabetic retinopathy (13–18). Retinal vasodilation has been proposed to occur before the onset of clinically evident diabetic retinopathy. An increase in retinal blood flow has been suggested to eventually lead to the development of diabetic retinopa- thy, possibly due to increased frictional forces (i.e., shear stress) on the endothelial cells lining the walls of retinal vessels (16). However, the precise nature of the blood flow disturbance is controversial, due, in part, to the diversity of techniques used to quantify retinal hemodynamics, the various stages of retinopathy studied, and the heterogene- ity of the diabetic groups (17). Bidirectional laser Doppler velocimetry is a technique used to quantify centerline blood velocity. The Canon Laser Blood Flowmeter (CLBF) is the only hemodynamic assessment technique that can simultaneously measure vessel diameter and centerline blood velocity and, there- fore, for the first time, quantify volumetric blood flow in absolute units (19). The CLBF determines centerline blood velocity (in millimeters per second) using bidirectional photodetectors and vessel diameter (in micromoles) using densitometry of the retinal arterioles and venules. In addition, an eye tracker system is incorporated into the optical system of the CLBF to minimize the impact of eye movement. It subsequently quantifies blood flow (in mi- croliters per minute) based on the Poiseuille principle. The minimum vessel diameter that the CLBF can measure is 80 m, and, therefore, the instrument cannot be used to assess capillary hemodynamics. The assessment of retinal blood flow with the CLBF will provide new insights into retinal vascular disease (20). Evaluation of the instrument in normal subjects to determine its variability and repeat- ability has been established (21,22). There is a need to reveal the precise nature of the disturbance of retinal hemodynamics in a defined population of patients with diabetes. The purpose of this study was to report baseline retinal arteriolar hemodynamics in a cohort of patients with varying levels of risk for the development of sight- threatening DME and to correlate these parameters to systemic measures of diabetes control and complications. RESEARCH DESIGN AND METHODS Research ethics approval was obtained from the research ethics board at the University Health Network, University of Toronto and the Office of Research From the 1 Department of Ophthalmology and Vision Science, University of Toronto, Toronto, Ontario, Canada; and the 2 School of Optometry, Faculty of Science, University of Waterloo, Waterloo, Ontario, Canada. Address correspondence and reprint requests to Chris Hudson, PhD, Department of Ophthalmology and Vision Science, University of Toronto, Toronto, Ontario M5T 2S8, Canada. E-mail: chudson@uwaterloo.ca. Received for publication 22 July 2005 and accepted in revised form 15 December 2005. CLBF, Canon Laser Blood Flowmeter; DME, diabetic macular edema; IOP, intraocular pressure. © 2006 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. 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