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In diabetic eye disease the factors leading to compromised circulation and the resulting loss of visual function are poorly understood. Although retinal circulation has been widely investigated, it accounts for only a fraction of total eye blood flow. Blood flow was investigated in the larger vessels feeding the eye in patients with early diabetic retinopathy.Eleven patients with early diabetes with minimal or no retinopathy and 11 healthy controls were evaluated for retrobulbar blood flow velocity using colour Doppler imaging for the ophthalmic and central retinal arteries. Patients and subjects were tested while breathing room air and again under conditions of isocapnic hyperoxia.Hyperoxia induced a significant change in the central retinal artery end diastolic velocity (EDV) (p = 0.008) and resistance index (RI) (p = 0.032) in normal subjects, but not in diabetic patients. Consequently, during hyperoxia, the diabetic patients were significantly higher for EDV (p = 0.006) and significantly lower for RI (p = 0.002) compared with normal controls. Hyperoxia caused no significant change in either group in the ophthalmic artery; nevertheless, under isocapnic hyperoxia conditions the diabetic patients had lower peak systolic velocity (p = 0.05) and lower RI (p = 0.05) than normal subjects.Imposition of isocapnic hyperoxia produces significant differences in the ophthalmic and central retinal artery blood flow velocities in diabetic patients with early disease when compared with normal subjects. These results demonstrate that diabetic patients with minimal or no retinopathy suffer from irregular ocular vascular function in the major vessels feeding the eye.