{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:05:16Z","timestamp":1789549516826,"version":"build-2803163510"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82271313"],"award-info":[{"award-number":["82271313"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Health Commission General Project","award":["202240026"],"award-info":[{"award-number":["202240026"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Chronic cerebral hypoperfusion triggers the development of white matter hyperintensities (WMHs), common in cerebral small vessel disease (CSVD). However, conventional imaging techniques cannot visualize cerebral small vessels. The retina, a direct extension of the central nervous system, has an unclear correlation with WMHs. This study employs Optical coherence tomographic angiography (OCTA) to investigate vascular changes in the retina and explore its correlation with WMHs, aiming to provide a new method for assessing perfusion in early ischemic brain WMHs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Forty-nine patients with WMHs were stratified into mild and moderate\/severe WMHs groups based on MRI findings, utilizing the Fazekas and Scheltens scales. OCTA assessed fundus vessel microcirculation. Logistic regression analyzed the correlation between ocular fundus microcirculation and WMH severity and location. Additionally, ROC curves evaluated the diagnostic efficacy of each fundus vascular microcirculation index in determining WMH severity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>After adjusting for multiple confounders, finding consistently indicated that the moderate\/ severe WMHs group exhibited lower vessel density (VD) in the superior quadrant of the inner peripapillary region compared to the mild group [OR = 0.487, CI (0.255,0.929), p &lt; 0.05]. ROC curves revealed that when combined with age, diabetes, and superior quadrant VD of the inner peripapillary region, specificity could be increased to 94.1%.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Peripapillary vessel density correlates closely with the severity of cerebral WMHs. Early morphological changes due to chronic hypoperfusion may initiate from the inner layer of the optic disc, and OCTA could offer a novel method for evaluating blood perfusion in ischemic WMHs.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0312534","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T17:33:32Z","timestamp":1730396012000},"page":"e0312534","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Peripapillary vessels density is closely related to cerebral white matter hyperintensities: An OCTA study"],"prefix":"10.1371","volume":"19","author":[{"given":"Yuanyue","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehua","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiqi","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"issue":"6","key":"pone.0312534.ref001","doi-asserted-by":"crossref","first-page":"278","DOI":"10.5694\/mja2.52079","article-title":"Consensus statement for the management of incidentally found brain white matter hyperintensities in general medical practice","volume":"219","author":"TP Ottavi","year":"2023","journal-title":"Medical Journal of Australia"},{"issue":"3","key":"pone.0312534.ref002","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1161\/01.STR.28.3.652","article-title":"Pathogenesis of Leukoaraiosis A Review","volume":"28","author":"L Pantoni","year":"1997","journal-title":"Stroke"},{"issue":"jul26 1","key":"pone.0312534.ref003","doi-asserted-by":"crossref","first-page":"c3666","DOI":"10.1136\/bmj.c3666","article-title":"The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis","volume":"341","author":"S Debette","year":"2010","journal-title":"Bmj"},{"issue":"2","key":"pone.0312534.ref004","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1172\/JCI39733","article-title":"Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease","volume":"120","author":"A Joutel","year":"2010","journal-title":"Journal of Clinical Investigation"},{"issue":"7","key":"pone.0312534.ref005","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1176\/appi.ajp.20220380","article-title":"Cerebral Small Vessel Disease Progression and the Risk of Dementia: A 14-Year Follow-Up Study","volume":"180","author":"MA Jacob","year":"2023","journal-title":"American Journal of Psychiatry"},{"issue":"1","key":"pone.0312534.ref006","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/WCO.0000000000000513","article-title":"New insights into cerebral small vessel disease and vascular cognitive impairment from MRI","volume":"31","author":"EE Smith","year":"2018","journal-title":"Current Opinion In Neurology"},{"issue":"5","key":"pone.0312534.ref007","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S1474-4422(13)70060-7","article-title":"Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging","volume":"12","author":"JM Wardlaw","year":"2013","journal-title":"The Lancet Neurology"},{"issue":"Suppl 1","key":"pone.0312534.ref008","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1159\/000051182","article-title":"Pathophysiologic mechanisms in the development of age-related white matter changes of the brain","volume":"9","author":"F Fazekas","year":"1998","journal-title":"Dementia and Geriatric Cognitive Disorders"},{"issue":"1","key":"pone.0312534.ref009","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1161\/01.STR.0000150668.58689.f2","article-title":"Anatomical Mapping of White Matter Hyperintensities (WMH)","volume":"36","author":"C DeCarli","year":"2005","journal-title":"Stroke"},{"key":"pone.0312534.ref010","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1148\/77.6.948","article-title":"Ophthalmic arteriography","volume":"77","author":"G. Di Chiro","year":"1961","journal-title":"Radiology"},{"issue":"5","key":"pone.0312534.ref011","first-page":"1217","article-title":"Vascularization of the human fetal retina: roles of vasculogenesis and angiogenesis","volume":"41","author":"S Hughes","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"pone.0312534.ref012","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2020.00521","article-title":"Structural and Microvascular Changes in the Macular Are Associated With Severity of White Matter Lesions","volume":"11","author":"C Peng","year":"2020","journal-title":"Frontiers in Neurology"},{"key":"pone.0312534.ref013","article-title":"Associations of macular microvascular parameters with cerebral small vessel disease in rural older adults: A population-based OCT angiography study","volume":"14","author":"Z Xu","year":"2023","journal-title":"Frontiers in Neurology"},{"issue":"1","key":"pone.0312534.ref014","article-title":"Retinal microvascular changes in white matter hyperintensities investigated by swept source optical coherence tomography angiography","volume":"22","author":"Y Gao","year":"2022","journal-title":"BMC Ophthalmology"},{"issue":"5","key":"pone.0312534.ref015","doi-asserted-by":"crossref","first-page":"e0268572","DOI":"10.1371\/journal.pone.0268572","article-title":"Reduced macular vessel density and inner retinal thickness correlate with the severity of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)","volume":"17","author":"C-W Lin","year":"2022","journal-title":"PloS One"},{"key":"pone.0312534.ref016","article-title":"Decreased retinal vascular density is associated with cognitive impairment in CADASIL: an optical coherence tomography angiography study","author":"Y Guo","year":"2024","journal-title":"Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology"},{"key":"pone.0312534.ref017","doi-asserted-by":"crossref","first-page":"100878","DOI":"10.1016\/j.preteyeres.2020.100878","article-title":"Plexus-specific retinal vascular anatomy and pathologies as seen by projection-resolved optical coherence tomographic angiography","volume":"80","author":"TT Hormel","year":"2021","journal-title":"Progress In Retinal and Eye Research"},{"issue":"2","key":"pone.0312534.ref018","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2214\/ajr.149.2.351","article-title":"MR signal abnormalities at 1.5 T in Alzheimer\u2019s dementia and normal aging","volume":"149","author":"F Fazekas","year":"1987","journal-title":"AJR American Journal of Roentgenology"},{"issue":"1","key":"pone.0312534.ref019","doi-asserted-by":"crossref","DOI":"10.1016\/0022-510X(93)90041-V","article-title":"A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging","volume":"114","author":"P Scheltens","year":"1993","journal-title":"Journal of the Neurological Sciences"},{"issue":"3","key":"pone.0312534.ref020","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/hbm.25695","article-title":"White matter hyperintensities segmentation using an ensemble of neural networks","volume":"43","author":"X Li","year":"2022","journal-title":"Human Brain Mapping"},{"issue":"4","key":"pone.0312534.ref021","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1161\/STROKEAHA.107.496091","article-title":"Retinal signs and stroke: revisiting the link between the eye and brain","volume":"39","author":"ML Baker","year":"2008","journal-title":"Stroke"},{"key":"pone.0312534.ref022","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2020.572484","article-title":"Decreased Retinal Vascular Density in Alzheimer\u2019s Disease (AD) and Mild Cognitive Impairment (MCI): An Optical Coherence Tomography Angiography (OCTA) Study","volume":"12","author":"X Wang","year":"2021","journal-title":"Frontiers in Aging Neuroscience"},{"issue":"1","key":"pone.0312534.ref023","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1001\/jama.288.1.67","article-title":"Cerebral white matter lesions, retinopathy, and incident clinical stroke","volume":"288","author":"TY Wong","year":"2002","journal-title":"JAMA"},{"issue":"Pt 7","key":"pone.0312534.ref024","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1093\/brain\/awq127","article-title":"Retinal microvascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study","volume":"133","author":"N Cheung","year":"2010","journal-title":"Brain: a Journal of Neurology"},{"issue":"Pt 1","key":"pone.0312534.ref025","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/brain\/awh688","article-title":"Retinal vessel diameters and cerebral small vessel disease: the Rotterdam Scan Study","volume":"129","author":"MK Ikram","year":"2006","journal-title":"Brain: a Journal of Neurology"},{"issue":"1","key":"pone.0312534.ref026","doi-asserted-by":"crossref","first-page":"3660","DOI":"10.1038\/s41598-022-07638-x","article-title":"Changes of the retinal and choroidal vasculature in cerebral small vessel disease","volume":"12","author":"CF Geerling","year":"2022","journal-title":"Scientific Reports"},{"issue":"2","key":"pone.0312534.ref027","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1177\/0271678X221135658","article-title":"Retinal capillary microvessel morphology changes are associated with vascular damage and dysfunction in cerebral small vessel disease","volume":"43","author":"SJ Wiseman","year":"2022","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"pone.0312534.ref028","doi-asserted-by":"crossref","first-page":"945964","DOI":"10.3389\/fnagi.2022.945964","article-title":"Retinal microvasculature and imaging markers of brain frailty in normal aging adults","volume":"14","author":"W Tao","year":"2022","journal-title":"Frontiers In Aging Neuroscience"},{"issue":"11","key":"pone.0312534.ref029","doi-asserted-by":"crossref","first-page":"e112311","DOI":"10.1371\/journal.pone.0112311","article-title":"Multimodal retinal vessel analysis in CADASIL patients","volume":"9","author":"F Alten","year":"2014","journal-title":"PloS One"},{"issue":"10","key":"pone.0312534.ref030","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1212\/01.WNL.0000033093.16450.5C","article-title":"Retinal arterial changes correlate with cerebral small-vessel disease","volume":"59","author":"VIH Kwa","year":"2002","journal-title":"Neurology"},{"issue":"8","key":"pone.0312534.ref031","doi-asserted-by":"crossref","first-page":"e2240","DOI":"10.1002\/brb3.2240","article-title":"Assessment of the outer retina and choroid in white matter lesions participants using swept-source optical coherence tomography","volume":"11","author":"WR Kwapong","year":"2021","journal-title":"Brain and Behavior"},{"issue":"8","key":"pone.0312534.ref032","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1111\/ene.15378","article-title":"Abnormalities of retinal structure and microvasculature are associated with cerebral white matter hyperintensities","volume":"29","author":"X Zhou","year":"2022","journal-title":"European Journal of Neurology"},{"key":"pone.0312534.ref033","doi-asserted-by":"crossref","first-page":"843198","DOI":"10.3389\/fneur.2022.843198","article-title":"Fundus Changes Evaluated by OCTA in Patients With Cerebral Small Vessel Disease and Their Correlations: A Cross-Sectional Study","volume":"13","author":"W Fu","year":"2022","journal-title":"Frontiers In Neurology"},{"issue":"9","key":"pone.0312534.ref034","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1007\/s10072-021-05038-z","article-title":"The vessel density of the superficial retinal capillary plexus as a new biomarker in cerebral small vessel disease: an optical coherence tomography angiography study","volume":"42","author":"X Wang","year":"2021","journal-title":"Neurological Sciences"},{"issue":"1","key":"pone.0312534.ref035","doi-asserted-by":"crossref","DOI":"10.1186\/s13195-024-01408-9","article-title":"Macular vessel density in the superficial plexus is not a proxy of cerebrovascular damage in non-demented individuals: data from the NORFACE cohort","volume":"16","author":"A Garc\u00eda-S\u00e1nchez","year":"2024","journal-title":"Alzheimers Res Ther"},{"issue":"5","key":"pone.0312534.ref036","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1111\/dom.15492","article-title":"Retinal vascular density as a potential biomarker of diabetic cerebral small vessel disease","volume":"26","author":"Y Huang","year":"2024","journal-title":"Diabetes, Obesity & Metabolism"},{"issue":"5","key":"pone.0312534.ref037","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S1350-9462(01)00005-2","article-title":"Blood flow in the optic nerve head and factors that may influence it","volume":"20","author":"SS Hayreh","year":"2001","journal-title":"Progress In Retinal and Eye Research"},{"issue":"3","key":"pone.0312534.ref038","first-page":"991","article-title":"Relaxation of retinal pericyte contractile tone through the nitric oxide-cyclic guanosine monophosphate pathway","volume":"35","author":"IO Haefliger","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"pone.0312534.ref039","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.exer.2015.02.011","article-title":"Optic nerve head biomechanics in aging and disease","volume":"133","author":"JC Downs","year":"2015","journal-title":"Exp Eye Res"},{"issue":"3","key":"pone.0312534.ref040","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3129\/i08-042","article-title":"Vascular anatomy of the optic nerve head","volume":"43","author":"PJ Mackenzie","year":"2008","journal-title":"Can J Ophthalmol"},{"issue":"4","key":"pone.0312534.ref041","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1136\/bjo.79.4.368","article-title":"Changes in the collagenous matrix of the aging human lamina cribrosa","volume":"79","author":"J Albon","year":"1995","journal-title":"Br J Ophthalmol"},{"issue":"4","key":"pone.0312534.ref042","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1167\/iovs.61.4.3","article-title":"Morphometric, Hemodynamic, and Biomechanical Factors Influencing Blood Flow and Oxygen Concentration in the Human Lamina Cribrosa","volume":"61","author":"T Chuangsuwanich","year":"2020","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"pone.0312534.ref043","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13195-020-00638-x","article-title":"Optical coherence tomography angiography as a potential screening tool for cerebral small vessel diseases","volume":"12","author":"J-Y Lee","year":"2020","journal-title":"Alzheimers Res Ther"},{"issue":"2","key":"pone.0312534.ref044","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1161\/01.STR.0000049766.26453.E9","article-title":"Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison, interrater agreement, and correlations with quantitative measurements","volume":"34","author":"P Kapeller","year":"2003","journal-title":"Stroke"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0312534","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T17:33:47Z","timestamp":1730396027000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0312534"}},"subtitle":[],"editor":[{"given":"Massimo","family":"Filippi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,10,31]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0312534","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,31]]}}}