Haemodynamic factors in the pathogenesis of diabetic retinopathy.

Objective- To examine the role of retinal haemodynamic factors in the pathogenesis of diabetic retinopathy. Design- (A) Laser Doppler velocimetry and computerised image analysis to: [i] Determine retinal blood flow in various grades of diabetic retinopathy. [ii] Define the autoregulatory capacity of the retinal circulation to an increase in perfusion pressure under conditions of relative normoglycaemia and hyperglycaemia. In this study, the mean arterial pressure (MAP) was increased by 15%, 30% and 40% above the baseline MAP using a Tyramine infusion. [iii] Define the autoregulatory capacity of the retinal circulation to a metabolic stimulus, breathing 60% oxygen, in a normotensive and hypertensive diabetic subjects under conditions of relative normoglycaemia and hyperglycaemia. (B) Ten year follow up of patients with background diabetic retinopathy in order to elucidate the clinical haemodynamic factors relating to progression to proliferative diabetic retinopathy and diabetic maculopathy. Results- (A) [i] Retinal blood flow was significantly increased in all grades of diabetic retinopathy (background 12.133.92ul/min, pre-proliferative 15.275.88ul/min, proliferative 13.884.51ul/min; p0.03) in comparison to nondiabetic subjects (9.523.18ul/min) and diabetic subjects with no retinopathy (9.123.83ul/min)(mean SD). [ii] The Coefficients of Autoregulation in the nondiabetic subjects were; 0.76 at 15% MAP increase, 0.91 at 30% MAP increase and 0.38 at 40% MAP increase. The respective values for the diabetic subjects at "normoglycaemia" were 1.00, 0.53 and 0.10 and at "hyperglycaemia" were 0.05, 0.08 and 0.00. [iii] In the normotensive non-diabetic subjects the oxygen reactivity was 41.1614.09%. It was significantly reduced in; normotensive "hyperglycaemic" diabetic subjects (21.7515.56%), hypertensive diabetic subjects with controlled blood pressure and "normoglycaemia" (30.4914.20%), hypertensive diabetic subjects with controlled blood pressure and "hyperglycaemia" (18.3611.42%), hypertensive diabetic subjects with uncontrolled blood pressure and "normoglycaemia" (26.9113.43%), hypertensive diabetic subjects with uncontrolled blood pressure and "hyperglycaemia" (17.1713.24%) (all p values 0.05, results as mean SD). (B) Comparing the lowest and highest quartiles of various risk factors, the following were found to confer an increased relative risk (p0.05) for progression to maculopathy alone (MAC) and proliferative retinopathy alone (PDR): increased systolic blood pressure (MAC x5.54, PDR x3.67), increased MAP (MAC x5.29), retinal perfusion pressure (MAC x9.14, PDR x4.06), pulse pressure (MAC x6.00, PDR x5.50), Hb A1% (MAC x4.31), serum cholesterol (MAC x7.71, PDR x4.43). Conclusions- Hyperperfusion of the retinal circulation has been found in all forms of untreated diabetic retinopathy. Abnormal retinal vascular autoregulation to an increase in systemic blood pressure and to a metabolic stimulus has been demonstrated in the diabetic retinal circulation particularly in the presence of hyperglycaemia. These abnormalities of the diabetic retinal circulation may be important in the pathogenesis of diabetic retinopathy. Consistent with the haemodynamic model is the evidence that systolic hypertension, increased retinal perfusion pressure, increased serum cholesterol and poor glycaemic control were related with progression to sight-threatening retinopathy. Effective management of hypertension, hyperglycaemia and hypercholesterolemia may reduce the vision loss due to diabetic retinopathy. (Abstract shortened by UMI.).