AIM: To perform a quantitative analysis of the peripapillary vessel density (VD) and retinal nerve fiber layer (RNFL) thickness changes in patients with early stage of diabetic retinopathy (DR). METHODS: In this case-control study, swept-source optical coherence tomography angiography (SS-OCTA) imaging was used to examine diabetic and age-matched healthy subjects. The optic disc HD 6×6 mm2 blood flow imaging scan mode was selected. Automatic software was used to measure the peripapillary VD, capillary vessel density (CVD), and RNLF in an optic nerve head (ONH) filed based on the Garway-Heath map. In addition, the correlation between peripapillary VD, CVD, and RNFL was further investigated. RESULTS: The cohort consisted of 32 healthy individuals and 72 patients with diabetes (34 eyes with no DR and 38 eyes with mild-moderate NPDR). Peripapillary VD decreased in the mild-moderate NPDR group compared to the control group in most regions (P<0.05). Peripapillary CVD and RNFL thickness were significantly lower in the mild-moderate NPDR group in the superior temporal (ST) quadrants (P=0.018, P=0.030). In the correlation analysis of each region, the RNFL thickness in the NS region was positively correlated with the peripapillary VD and CVD (r=0.233, P=0.05; r=0.288, P=0.015). In the TI region, the RNFL thickness was positively correlated with the peripapillary CVD (r=0.237, P=0.047). CONCLUSION: The measurement based on the ONH topographic map may be helpful in detecting functional and structural impairments in DR. The peripapillary VD, CVD and RNFL decrease in early DR, and the RNFL thickness altered in association with the CVD or/and VD in some regions.