Purpose: To investigate layer specific retinal vascular reactivity (RVR) in capillaries of diabetic subjects without DR or with only mild non-proliferative diabetic retinopathy (NPDR).
Methods: A previously described nonrebreathing apparatus was used to deliver room air, 5% CO2, or 100% O2 to 41 controls and 22 diabetic subjects (with mild or no NPDR) while simultaneously acquiring fovea-centered 3x3mm2 Swept-Source Optical Coherence Tomography Angiography (SS-OCTA) images. Vessel skeleton density (VSD) and vessel diameter index (VDI) were calculated for each gas condition for the superficial retinal layer (SRL) and deep retinal layer (DRL). The superficial layer analysis excluded arterioles and venules. Data analysis was performed using mixed factorial analysis of covariance stratified by diabetic status. All models were adjusted for age, gender, and hypertension, and statistical significance for multiple comparisons from posthoc comparisons were defined at p<0.017.
Results: Among controls, there was a significant difference in capillary VSD between all gas conditions (p<0.001). This difference was present in both the SRL and DRL. Among diabetics, there was no significant difference in response to CO2 conditions in the SRL (p = 0.072), and a blunted response to both CO2 (p = 0.9) and O2 in the DRL (p = 0.019). A significant gas effect was detected in the capillary VDI in the SRL of controls (p = 0.001), which was driven by higher VDI in the oxygen condition compared to that of carbon dioxide.
Conclusions: Impairment in RVR in diabetic subjects is characterized by a paradoxical response to CO2 in both the SRL and DRL as well as an attenuated response to O2 in the DRL. These layer and gas specific impairments in diabetics seem to occur early in the disease and to be driven primarily at the capillary level.