Frontiers in neurology · 2025
Diffusion tensor imaging along the perivascular space may reveal potential pathological mechanisms underlying disease progression in primary open-angle glaucoma patients.
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Chen Yilei, Xiao Shuyu, Yan Lvyu, Gong Zhigang, Huang Yanwen, Tan Wenli, Yu Ying
Аннотация
PURPOSE: This study investigates glymphatic system dysfunction in primary open-angle glaucoma (POAG) patients and explores its potential role in the progressive decline of visual function associated with the disease.
METHODS: This prospective study compared 47 primary open-angle glaucoma (POAG) patients and 50 healthy controls (HCs) using multimodal MRI, including DTI, T1/T2-weighted imaging, and resting-state fMRI. Group differences in brain morphometry, spontaneous activity, perivascular space (PVS) volume, and DTI-ALPS index were analyzed, with regression and mediation models exploring their relationships. Ocular parameters (intraocular pressure, RNFL thickness, cup-to-disc ratio, visual field) were correlated with fMRI findings, particularly PVS and ALPS metrics.
RESULTS: Compared to HCs, POAG patients exhibited significantly reduced cortical thickness, lower volume-wise Resting-state fMRI (Rs-fMRI) concordance (p < 0.001) and voxel-wise Rs-fMRI concordance (p < 0.05) in local intracranial regions, lower bilateral ALPS indices (p < 0.001), and higher volume fraction of the lateral ventricle body perivascular space (LVB-PVS) (p < 0.001). Linear regression models showed significant associations among left RNFL thickness, left ALPS index, LVB-PVS volume fraction, and cortical thickness of the left lingual gyrus (LING.L) (p < 0.05). Mediation analysis revealed that the left ALPS index partially mediated the associations between volume-wise Rs-fMRI concordance, cortical thickness of LING.L, and RNFL thickness. Furthermore, the ALPS index significantly mediated the relationship between LING.L cortical thickness and LVB-PVS volume fraction. However, no significant correlation was found between ALPS and the degree of visual field defect.
CONCLUSION: The reduced ALPS index in POAG patients suggests impaired glymphatic clearance, which may impair metabolic clearance and contribute to RNFL damage, influencing disease progression.
METHODS: This prospective study compared 47 primary open-angle glaucoma (POAG) patients and 50 healthy controls (HCs) using multimodal MRI, including DTI, T1/T2-weighted imaging, and resting-state fMRI. Group differences in brain morphometry, spontaneous activity, perivascular space (PVS) volume, and DTI-ALPS index were analyzed, with regression and mediation models exploring their relationships. Ocular parameters (intraocular pressure, RNFL thickness, cup-to-disc ratio, visual field) were correlated with fMRI findings, particularly PVS and ALPS metrics.
RESULTS: Compared to HCs, POAG patients exhibited significantly reduced cortical thickness, lower volume-wise Resting-state fMRI (Rs-fMRI) concordance (p < 0.001) and voxel-wise Rs-fMRI concordance (p < 0.05) in local intracranial regions, lower bilateral ALPS indices (p < 0.001), and higher volume fraction of the lateral ventricle body perivascular space (LVB-PVS) (p < 0.001). Linear regression models showed significant associations among left RNFL thickness, left ALPS index, LVB-PVS volume fraction, and cortical thickness of the left lingual gyrus (LING.L) (p < 0.05). Mediation analysis revealed that the left ALPS index partially mediated the associations between volume-wise Rs-fMRI concordance, cortical thickness of LING.L, and RNFL thickness. Furthermore, the ALPS index significantly mediated the relationship between LING.L cortical thickness and LVB-PVS volume fraction. However, no significant correlation was found between ALPS and the degree of visual field defect.
CONCLUSION: The reduced ALPS index in POAG patients suggests impaired glymphatic clearance, which may impair metabolic clearance and contribute to RNFL damage, influencing disease progression.