Diameter changes of retinal vessels during acute hypoxia in vivo are modified by inhibiting NO and prostaglandin synthesis. The evidence points to possible new targets of intervention on the diameter regulation of retinal arterioles in diseases where retinal hypoxia is part of the disease pathogenesis.

Background: Acute hypoxia induces retinal vasodilatation, which depends on cyclooxygenase (COX) products and nitric oxide (NO) in vitro. However, it is unknown whether these mechanisms are active in diabetic patients and may contribute to the development of diabetic retinopathy. Methods: The Dynamic Vessel Analyzer was used to study the diameter regulation in retinal vessels during hypoxia in type 1 diabetic patients without retinopathy. The influence of NO and COX synthesis inhibition on the diameter of larger retinal vessels was studied during hypoxia, during isometric exercise and during flicker stimulation. Results: Increased arterial blood pressure during L-NMMA infusion and isometric exercise were paralleled by constriction of the retinal arterioles suggesting normal pressure autoregulation. Hypoxia significantly reduced the diameter responses during isometric exercise and during flicker stimulation as compared to normal persons. Conclusion: The findings support that changes in metabolic autoregulation develop before changes in pressure autoregulation in diabetic patients.

Diameter regulation of retinal vessels during hypoxia in normal persons can be influenced by the inhibition of COX products, but not by increasing the NO concentration. The findings suggest that the vasoactive effects of NO on retinal arterioles during hypoxia are saturated in normal persons.

Hypoxia-induced dilatation of retinal arterioles is severely reduced in patients with diabetic maculopathy. Future intervention studies aimed at normalizing the diameter regulation of retinal arterioles in diabetic patients should preferentially be conducted in the early stages of the disease where the potential for changing the vessel diameter is preserved. ClinicalTrials.gov identifier: NCT01689090.

PURPOSE. Diabetic retinopathy is characterized by disturbances in retinal blood flow mediated by capillary occlusion, intraretinal microvascular abnormalities (IRMAs), neovascularizations, and omega loops and reduplications. It is likely that the study of oxygen saturation in these abnormalities can provide knowledge about their role in the development of diabetic retinopathy. METHODS. The oxygen saturation in IRMA vessels and venous loops and reduplications were studied in 40 diabetic patients with severe nonproliferative or proliferative diabetic retinopathy. The saturation values in the studied vascular abnormalities were compared to those of the larger retinal arterioles and venules. RESULTS. There was a similar oxygen saturation (mean 6 SD) in IRMAs observed to connect arterioles with venules (78.6% 6 11.8%, n ¼ 22) and IRMAs connecting venules with venules (79.2% 6 9.0%, n ¼ 12; P > 0.999). The saturation in IRMAs was significantly lower (P < 0.0002) than in arterioles (97.4% 6 5.2%, n ¼ 40) and significantly higher (P < 0.0001) than the saturation in omega loops and reduplications (54.2% 6 19.3%, n ¼ 6), which in turn showed no significant difference from the saturation in the venules (61.8% 6 6.8%, n ¼ 40, P ¼ 0.4). CONCLUSIONS. The findings suggest that the oxygen saturation in vascular abnormalities in diabetic retinopathy depends on the extent of arteriovenous (A-V) shunting, with venous saturation due to no A-V shunting in venous loops and reduplications, and intermediate oxygen saturation due to moderate shunting in IRMAs. This may precede the development of neovascularizations with arterial oxygen saturation due to high A-V shunting.