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Purpose Diabetic retinopathy (DR) is a common cause of vision loss in working age adults and presents changes in retinal vessel oxygenation and morphology. The purpose of this study was to test the hypothesis that there is an association of retinal vessel oxygen saturation with vessel density (VD) and tortuosity in DR. Methods Ninety-five subjects were classified in the following groups: nondiabetic control ( N = 25), no DR ( N = 28), mild nonproliferative DR (NPDR; N = 21), moderate to severe NPDR ( N = 14), or treated proliferative DR (PDR; N = 7). Retinal oximetry was performed to measure arterial and venous oxygen saturation (SO 2A and SO 2V ) and calculate oxygen extraction fraction (OEF). Optical coherence tomography angiography (OCTA) was performed for measurements of VD and vessel tortuosity index (VTI). Results There were statistically significant differences in SO 2A and SO 2V among groups ( P < 0.004). SO 2A and SO 2V were higher in the PDR group compared to the control group and SO 2V was also higher in the moderate to severe NPDR group. VD differed significantly among groups ( P = 0.003), whereas VTI was not significantly different ( P = 0.22). Compared to the control group, VD was lower in moderate to severe NPDR and PDR groups. VD was also lower in the PDR group than that in the no DR group ( P = 0.03). There was a significant correlation of VTI with SO 2V (r = 0.32, P = 0.002) and OEF (r = −0.35, P = 0.001). Conclusions Retinal vessel morphology, oxygenation, and tissue oxygen extraction were associated with each other in a cohort of subjects with and without DR. Translational Relevance The findings of this study have the potential to improve clinical management of DR by providing better understanding of human disease pathophysiology and propelling future studies to identify multiple image-based biomarkers for improved disease diagnosis and monitoring.

Purpose: Retinal ischemia has been implicated in vision-threatening diseases. Permanent bilateral common carotid artery occlusion (BCCAO) studies have reported retinal degeneration and gliosis, as well as cerebral degeneration. We hypothesized that BCCAO-induced long-term (3 to 14 days) impairments to oxygen delivery (DO 2 ), extraction fraction (OEF), and metabolism (MO 2 ) affect cellular morphology and biochemical pathways. Methods: Twenty-one rats underwent BCCAO or sham surgery. Blood flow and vascular oxygen tension imaging was performed in both eyes. Images were analyzed to derive retinal arterial and venous oxygen contents (O 2A , O 2V ), arteriovenous oxygen content difference (O 2AV ), and total retinal blood flow (TRBF). The following equations were used: DO 2 =TRBF*O 2A ; MO 2 =TRBF*O 2AV ; OEF=MO 2 /DO 2 . After imaging, immunohistochemistry and histological assays were performed on retinal sections. Results: Compared to the sham group, DO 2 was reduced in 3-day (β=-622 nLO 2 /min), 7-day (β=-614 nLO 2 /min), and 14-day (β=-605 nLO 2 /min) BCCAO groups. MO 2 was reduced in 3-day (β=-215 nLO 2 /min), 7-day (β=-256 nLO 2 /min), and 14-day (β=-262 nLO 2 /min) BCCAO groups. Compared to the sham group, OEF was increased in 3-day (β=0.405) and 7-day (β=0.209) BCCAO groups. Compared to the sham group, the thickness of the nerve fiber (β=-14.6 μm), inner nuclear (β=-7.21 μm), outer plexiform (β=-6.70 μm), and inner retina (β=-30.7 μm) layers were decreased, while thickness of the outer nuclear layer was increased (β=7.88 μm) in the 14-day BCCAO group. Gliosis was increased in the 14-day BCCAO group compared to all other groups. Compared to the sham group, TUNEL-positive cells in inner and outer nuclear layers were increased in the 3-day BCCAO group. Conclusions: The findings confirm our hypothesis that BCCAO-induced reduction in retinal DO 2 resulted in increased OEF, impairment of MO 2 , and inner retinal cell death after 3 days, whereas increased gliosis and degeneration of inner retinal cells were observed after 14 days. When compared to brain literature, the retina—an extension of the diencephalon-- showed a similar reduction in blood flow and increase in both OEF and cell-death at 3-days following BCCAO.