A preliminary study of subcortical gray matter nucleus volumetric and morphological changes in diabetic retinopathy

Diabetic retinopathy (DR), a microvascular complication of diabetes, exhibits early neurodegeneration. Retinal and cerebrovascular homology links DR microcirculatory abnormalities to cognitive impairment risk. This study analyzes subcortical gray matter changes in DR patients, providing neuroimaging evidence for central nervous system complications.

In total, 32 patients with DR and 38 normal controls were recruited and underwent T1-weighted imaging three-dimensional (3D)-magnetization‑prepared rapid acquisition gradient echo scanning. Subcortical gray matter nuclei were automatically segmented using Freesurfer software, and volumetric comparisons of these nuclei were further performed with SPSS 26.0 software. Vertex-based shape analysis was employed to compare morphological differences in gray matter nuclei (including the thalamus, caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens) between the two groups. Group-level statistical results were derived using non-parametric permutation tests (1,000 iterations), followed by family-wise error correction for multiple comparisons via threshold-free cluster enhancement (TFCE). Statistical significance was defined as a TFCE-corrected P<0.05. Morphological parameters reflecting structural changes in each nucleus were extracted. A partial correlation analysis was performed between the volume value and deformation value and cognitive and neuropsychological assessment scale scores, fasting blood glucose, glycated hemoglobin, and other biochemical indicators.

The covariance analysis results indicated that compared with the control group, the DR patients showed atrophy in the left thalamic volume (P<0.05). The vertex-based morphological analysis showed that compared with the control group, the morphology of the caudate nucleus in DR group demonstrated inward contraction in the medial region of the body tail and outward expansion in the dorsolateral region. The morphologic atrophy of the thalamic nuclei was concentrated in the posteromedial [dorsalis medialis (DM)] and thalamic occipital [pulvinar (Pu)] region, while distension was observed in the ventral region (all TFCE-corrected P<0.05). The partial correlation analysis revealed that in the DR patients, the gray matter volume values of the bilateral thalamus were negatively associated with disease duration (r=-0.517, P=0.005; r=-0.412, P=0.029); while the deformation index value of the right thalamus was negatively correlated with the Mini-Mental State Examination score (r=-0.433, P=0.013); and the deformation index value of the right caudate nucleus was negatively correlated with the Self-rating Depression Scale index (r=-0.480, P=0.005).

The subcortical gray matter nuclei of patients with DR undergo volumetric and morphological abnormal changes. Abnormal changes in these regions provide imaging evidence of the changes in brain structure and neuropathological progression in DR patients, as well as a visual basis for the clinical realization of targeted interventions and treatments to delay cognitive decline.