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Given the vascular and CSF links between the eye and brain, this study explored whether retinal vascular morphology can indicate cerebrovascular injury and CP dysfunction in SVD. We assessed SVD burden using imaging phenotypes like white matter hyperintensities (WMH), perivascular spaces, lacunes, and microbleeds. Cerebrovascular injury was quantified by WMH volume and peak width of skeletonized mean diffusivity (PSMD), while CP volume measured its dysfunction. Retinal vascular markers were derived from fundus images, with associations analyzed using generalized linear models and Pearson correlations. Path analysis quantified contributions of cerebrovascular injury and CP volume to retinal changes. Support vector machine models were developed to predict SVD severity using retinal and demographic data. Among 815 participants, 578 underwent ocular imaging. Increased SVD burden markedly correlated with both cerebral and retinal biomarkers, with retinal alterations equally influenced by cerebrovascular damage and CP enlargement. Machine learning models showed robust predictive power for severe SVD burden (AUC was 0.82), PSMD (0.81), WMH volume (0.77), and CP volume (0.80). These findings suggest that retinal imaging could serve as a cost-effective, noninvasive tool for SVD screening based on vascular and CSF connections.<\/jats:p>","DOI":"10.34133\/research.0633","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T06:33:41Z","timestamp":1739860421000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":20,"title":["Retinal Vascular Morphology Reflects and Predicts Cerebral Small Vessel Disease: Evidences from Eye\u2013Brain Imaging Analysis"],"prefix":"10.34133","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4446-0338","authenticated-orcid":false,"given":"Ning","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Medical Imaging, Yanjing Medical College, \rCapital Medical University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingze","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for MRI Research, Academy for Advanced Interdisciplinary Studies, \rPeking University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuohua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kailuan General Hospital, Tangshan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouling","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kailuan General Hospital, Tangshan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, \rTsinghua University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Radiology, Kailuan General Hospital, Tangshan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology, \rCapital Medical University Affiliated Beijing Friendship Hospital, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenchang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology, \rCapital Medical University Affiliated Beijing Friendship Hospital, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9559-4777","authenticated-orcid":true,"given":"Han","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Radiology, \rCapital Medical University Affiliated Beijing Friendship Hospital, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"e_1_3_4_2_2","first-page":"189","article-title":"Clearance dysfunction of trans-barrier transport and lymphatic drainage in cerebral small vessel disease: Review and prospect","author":"Zhu H-H","year":"2023","unstructured":"Zhu H-H, Li S-S, Wang Y-C, Song B, Gao Y, Xu Y-M, Li Y-S. 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