PurposeOxygen saturation (sO2) plays a critical role in retinal pathophysiology, especially at the macula, which undergoes significant energy consumption. While macular damage has been suggested to be involved in early-stage glaucoma, there has been no report to date on non-invasive macular sO2in glaucoma. Therefore, we conducted this study to compare macular sO2associated with other clinical measurements between normal and glaucoma subjects and evaluate whether there are significant differences.MethodThis is a cross-sectional study. We used visible light optical coherence tomography (VIS-OCT) for retinal oximetry in perifoveal vessels. The subjects from groups of normal, suspect/pre-perimetric glaucoma (GS/PPG) and perimetric glaucoma (PG) were scanned using VIS-OCT in the macular region with a sampling density of 512×256 in an area of 5×5 mm2. 48 eyes (16 normal, 17 GS/PPG and 15 PG) were included for the analysis. For each eye, we measured the sO2of arterioles (AsO2), venules (VsO2), and calculated the difference between arterioles and venules (A-V sO2=AsO2-VsO2), oxygen extraction (OE=(AsO2-VsO2)/AsO2×100%). Additionally, we included Zeiss Cirrus OCT scans and 24-2 visual field test (VFT) for clinical benchmark. One-way ANOVA was used to compare the differences among the three groups. Spearman correlation tests were used for correlation sO2markers to standard metrics including the thickness of ganglion cell layer and inner plexiform layer (GCL+IPL), circumpapillary retinal nerve fiber layer (cpRNFL) and mean deviation (MD) in VFT.ResultSignificant differences were found among three groups for all VIS-OCT, Zeiss OCT, and VFT variables. Macular AsO2, A-V sO2, OE decreased, and VsO2increased along with severity. Macular AsO2and A-V sO2were statistically correlated with GCL+IPL and cpRNFL in all eyes, as well as only PG eyes. Within PG eyes, the correlation between AsO2and GCL+IPL is dominant in more damaged lower hemifield.ConclusionThe GS/PPG and PG subjects had significantly higher macular VsO2, lower A-V sO2and OE indicating less oxygen consumption. The sO2measured by retinal oximetry of VIS-OCT can be a potential metric for the early diagnosis of glaucoma.