© The Author(s) 2022.Purpose: To compare the translaminar pressure difference (TLPD), anterior lamina cribrosa surface depth (ALCSD), lamina cribrosa thickness (LCT), lamina cribrosa curvature index (LCCI) and peripapillary vascular density (pVD) in diabetic and healthy subjects. Methods: Two hundred and eighty eyes of 140 patients (79 patients with diabetes mellitus (DM) without diabetic retinopathy (DR) and 61 healthy subjects) were enrolled in this study. Full ophthalmological examination, as well as optical coherence tomography (OCT) and OCT angiography (OCT-A) images, were analyzed. The ALCSD, LCT, LCCI were measured by enhanced depth imaging (EDI) OCT and the pVD by OCT-A. The TLPD values and relationships between TLPD and lamina cribrosa features and pVD were investigated in all subjects. Results: The ALCSD and LCT were significantly shallower and thinner in diabetic patients when compared to healthy subjects (p <0.001). There was no significant difference in the LCCI in diabetics 13.717 (5.74–33.91) vs healthy subjects 13.118 (5.53–27.05) (p = 0.181). OCT-A revealed that the pVD in the diabetic group was significantly lower than in the non-diabetic group (p <0.001). TLPD was significantly lower in diabetic patients compared to healthy controls. Conclusion: There are early changes in pVD and peripapillary vessel morphology in patients with DM. ALCSD and LCT were shallower and thinner in diabetic patients whereas the LCCI did not differ significantly. LCCI may be more valuable in assessing the lamina cribrosa (LC) of diabetic patients. The TLPD was found to be lower in diabetic patients compared to normal controls.