PurposeTo assess the relationship between the change of optic disc vessel density (ODVD) and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients. DesignRetrospective case series. MethodsFor 105 POAG patients, ≥ 5 consecutive optical coherence tomography (OCT) and OCT angiography (OCTA) images were obtained during ≥ 2 years of follow-up.Based on enface OCTA imaging, ODVD was calculated as the ratio of pixels occupied by vessels below the internal limiting membrane within the temporal area of the optic cup, and ODVD reduction was determined when there was a statistically significant negative slope (P < 0.05) for any of the global, superior, or inferior sectors. The association between the rates of ODVD change and RNFL thinning was assessed by multivariable longitudinal linear mixed-effects model vs. time. ResultsDuring 2.9 ± 0.3 years of follow-up on the 105 participants with visual field mean deviation at baseline of 5.7 ± 4.8 dB, 46 (43.8%) showed ODVD reduction. Faster global RNFL thinning was associated with the smaller Bruch's membrane opening area (ß = 0.381; 95% confidence interval (CI), 0.120 to 0.646; P = 0.006), optic disc hemorrhage (ß = -0.567; 95% CI, -0.909 to -0.228; P = 0.002) and faster rate of global ODVD change (ß = -0.090; 95% CI, -0.139 to -0.042; P = 0.001). ConclusionsReduction of optic disc microvasculature was associated with rapid RNFL thinning in POAG. This suggests a role for deep ONH circulation in the glaucoma pathogenesis.