BACKGROUND: Diabetic retinopathy (DR), characterized by retinal microvascular and neuroglial network damage, results from prolonged hyperglycemia. Non-proliferative DR (NPDR) frequently presents asymptomatically, complicating its early detection. This pilot study explored the use of advanced ultrasound techniques, specifically super-resolution imaging (SRI) and shear wave elastography (SWE), to non-invasively diagnose NPDR. METHODS: A total of 34 patients with NPDR and 32 patients with non-DR (NDR) underwent routine, two-dimensional (2D) ultrasound to measure eye axial length and structure. Color Doppler was used to assess the posterior eye blood flow. SWE was used to measure the optic nerve stiffness. SRI was used to image the fundus microcirculation. Lastly, the parameters were compared between groups. RESULTS: The NPDR group had greater optic nerve stiffness and lower microvascular density at the optic disc (both P<
0.05). Receiver operating characteristic (ROC) analysis revealed that optic nerve elastic Young's modulus mean (Emean) >
7.33 kPa and microvascular density <
42.99% suggest NPDR, with microvascular density having the highest diagnostic value. The microvascular density was significantly negatively correlated with the Emean (R=-0.83
P<
0.002). CONCLUSIONS: SRI and SWE were used in this pilot study to quantify vascular and optic nerve abnormalities in patients with NPDR. The detection of early microcirculatory changes and increased optic nerve stiffness has introduced innovative, non-invasive methods for the early diagnosis of NPDR.