{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:22:02Z","timestamp":1781623322830,"version":"3.54.5"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Shanghai Science and Technology Committee","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to HCs, POAG patients exhibited significantly reduced cortical thickness, lower volume-wise Resting-state fMRI (Rs-fMRI) concordance (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001) and voxel-wise Rs-fMRI concordance (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05) in local intracranial regions, lower bilateral ALPS indices (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), and higher volume fraction of the lateral ventricle body perivascular space (LVB-PVS) (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001). 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) (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05). 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The reduced ALPS index in POAG patients suggests impaired glymphatic clearance, which may impair metabolic clearance and contribute to RNFL damage, influencing disease progression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1659200","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T04:17:37Z","timestamp":1759897057000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Diffusion tensor imaging along the perivascular space may reveal potential pathological mechanisms underlying disease progression in primary open-angle glaucoma patients"],"prefix":"10.3389","volume":"16","author":[{"given":"Yilei","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lvyu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global 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