Keywords
White matter hyperintensities
Retinal ganglion cell layer
Optical coherence tomography
Submitted : 2026-06-09
Accepted : 2026-06-24
Published : 2026-07-09
Abstract
Objective: To investigate the correlation between the thickness of the retinal ganglion cell layer (GCL) measured by optical coherence tomography (OCT) and the severity of white matter hyperintensities (WMH) in cerebral small vessel disease (CSVD). Methods: Thirty-one patients with CSVD were selected and divided into a mild group (21 cases) and a moderate-to-severe group (10 cases) based on the severity of WMH. Additionally, 30 healthy individuals were selected as the control group. All subjects underwent 3.0T cranial MRI and OCT examinations. The severity of WMH was assessed using the Fazekas scale, and the thickness of the GCL in each quadrant, as well as the average and minimum thickness, was measured to analyze their correlation with WMH and their predictive value. Results: Statistically significant differences were observed among the three groups in terms of GCL thickness in the superior nasal, inferior nasal, inferior, and inferior temporal quadrants, as well as the average and minimum thickness (P < 0.05). The average GCL thickness showed a significant negative correlation with the Fazekas score (P < 0.05). Multiple linear regression analysis revealed that the average GCL thickness in the moderate-to-severe WMH group was significantly lower than that in the mild group (P < 0.05), and type 2 diabetes mellitus enhanced this negative correlation. The ROC curve demonstrated that after adjusting for clinical factors, the area under the curve (AUC) for predicting moderate-to-severe WMH using the average GCL thickness reached 0.83. Conclusion: The thickness of the GCL in patients with CSVD is negatively correlated with the severity of WMH, and the average GCL thickness has good predictive value for moderate-to-severe WMH. Meanwhile, OCT, as a non-invasive fundus imaging technique, can provide a new method for the early identification of CSVD and the assessment of white matter lesions.
References
Hong H, Tozer DJ, Chen Y, et al., 2025, Perivascular Space Dysfunction in Cerebral Small Vessel Disease is Related to Neuroinflammation. Brain, 148(5): 1540–1550.
Hu HY, Ou YN, Shen XN, et al., 2021, White Matter Hyperintensities and Risks of Cognitive Impairment and Dementia: A Systematic Review and Meta-analysis of 36 Prospective Studies. Neuroscience & Biobehavioral Reviews, 2021(120): 16–27.
Luo W, Dai Z, Wu W, et al., 2025, White Matter Hyperintensities and the Risk of Vascular Dementia: A Systematic Review and Meta-analysis. PeerJ, 2025(13): e19460.
Divecha YA, Rampes S, Tromp S, et al., 2025, The Microcirculation, the Blood-brain Barrier, and the Neurovascular Unit in Health and Alzheimer Disease: The Aberrant Pericyte is a Central Player. Pharmacological Reviews, 77(3): 100052.
Lee JY, Kim JP, Jang H, et al., 2020, Optical Coherence Tomography Angiography as a Potential Screening Tool for Cerebral Small Vessel Diseases. Alzheimer’s Research & Therapy, 12(1): 73.
Ashimatey BS, D’Orazio LM, Ma SJ, et al., 2020, Lower Retinal Capillary Density in Minimal Cognitive Impairment among Older Latinx Adults. Alzheimer’s & Dementia (Amsterdam, Netherlands), 12(1): e12071.
Wang X, Wei Q, Wu X, et al., 2021, The Vessel Density of the Superficial Retinal Capillary Plexus as a New Biomarker in Cerebral Small Vessel Disease: An Optical Coherence Tomography Angiography Study. Neurological Sciences, 42(9): 3615–3624.
Song Y, Lai Z, Ding K, et al., 2024, Peripapillary Vessels Density is Closely Related to Cerebral White Matter Hyperintensities: An OCTA Study. PLoS One, 19(10): e0312534.
Qu M, Kwapong WR, Peng C, et al., 2020, Retinal Sublayer Defect is Independently Associated with the Severity of Hypertensive White Matter Hyperintensity. Brain and Behavior, 10(2): e01521.
Gibbon S, Low A, Hamid C, et al., 2024, Association of Optic Disc Pallor and RNFL Thickness with Cerebral Small Vessel Disease in the PREVENT-Dementia Study. Alzheimer’s & Dementia (Amsterdam, Netherlands), 16(3): e12633.
Sui J, Li H, Bai Y, et al., 2024, Morphological Characteristics of the Foveal Avascular Zone in Pathological Myopia and its Relationship with Macular Structure and Microcirculation. Graefe’s Archive for Clinical and Experimental Ophthalmology, 262(7): 2121–2133.
Liu F, Niu L, Guo J, et al., 2023, Quantitative Evaluation of Retinal and Choroidal Vascularity and Retrobulbar Blood Flow in Patients with Myopic Anisometropia by CDI and OCTA. British Journal of Ophthalmology, 107(8): 1172–1177.
Huang Y, Wang S, Cai C, et al., 2024, Retinal Vascular Density as a Potential Biomarker of Diabetic Cerebral Small Vessel Disease. Diabetes, Obesity and Metabolism, 26(5): 1789–1798.
Nelis P, Kleffner I, Burg MC, et al., 2018, OCT-Angiography Reveals Reduced Vessel Density in the Deep Retinal Plexus of CADASIL Patients. Scientific Reports, 8(1): 8148.
Wiseman SJ, Zhang JF, Gray C, et al., 2023, Retinal Capillary Microvessel Morphology Changes are Associated with Vascular Damage and Dysfunction in Cerebral Small Vessel Disease. Journal of Cerebral Blood Flow & Metabolism, 43(2): 231–240.