{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:57:53Z","timestamp":1785463073772,"version":"3.56.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To quantify optical coherence tomography (OCT)-derived retinal layer reflectivity and retinal thickness changes in acute central retinal artery occlusion (CRAO) for rapid diagnosis and stratification of ischemic tissue state, referenced to the clinically relevant 4.5-h window for reperfusion therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective multicenter study included 39 patients with unilateral acute non-arteritic CRAO imaged by OCT within 48 h of reliably reported symptom onset. Five horizontal macular B-scans per eye [central (foveal), two superior, two inferior] were analyzed. Inner retinal layers (IRL) and outer retinal layers (ORL) were manually segmented. Mean grayscale reflectivity was extracted from predefined regions of interest and summarized as the within-eye IRL\/ORL reflectivity ratio. Retinal thickness was obtained from Early Treatment Diabetic Retinopathy Study (ETDRS) sectors; relative retinal thickness increase (RRTI) was defined as CRAO-eye thickness divided by fellow-eye thickness. Diagnostic performance (CRAO vs. fellow eye) and classification relative to the 4.5-h reference (&amp;lt; 4.5 vs. \u2265 4.5 h) were assessed using receiver operating characteristic (ROC) analyses and non-parametric testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The within-eye IRL\/ORL reflectivity ratio reliably distinguished CRAO-affected eyes from fellow eyes across all macular scan locations (AUC = 0.98\u20130.99;\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). Retinal thickness increased in CRAO eyes across all ETDRS sectors except the foveal center, with sector-wise diagnostic performance ranging from AUC 0.78\u20130.99. Both reflectivity- and thickness-based metrics demonstrated time dependence: the IRL\/ORL reflectivity ratio increased with time-to-OCT in CRAO eyes (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      0.43\u20130.54) and discriminated &amp;lt; 4.5 vs. \u22654.5 h (AUC 0.88\u20130.91). Inter-eye analyses indicated that temporal separation was primarily driven by progressive attenuation of ORL reflectivity, whereas IRL hyperreflectivity was established early and remained comparatively stable. Retinal thickness and RRTI increased with ischemia duration across ETDRS sectors, with strongest temporal discrimination in inferior sectors (S8; optimal RRTI cut-off \u2248 1.20).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Quantitative OCT biomarkers based on within-eye reflectivity redistribution and retinal edema enable accurate diagnosis of acute CRAO and provide objective imaging-based information on ischemic tissue state, referenced to the 4.5-h therapeutic window. These rapidly obtainable measures may support acute stroke triage and telemedical workflows. Prospective validation, particularly in unknown-onset CRAO, is warranted before clinical implementation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1783055","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:33:03Z","timestamp":1778214783000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Retinal layer reflectivity and thickness as OCT biomarkers for diagnosis and imaging-based stratification relative to the 4.5-h window in acute central retinal artery occlusion"],"prefix":"10.3389","volume":"17","author":[{"given":"Alessandra","family":"Walter","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Clinica Baviera-AIER Eye Hospital Group","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Poli","sequence":"additional","affiliation":[{"name":"Department of Neurology, District Hospital Calw-Nagold, Clinics Calw","place":["Calw, Germany"]},{"name":"Department of Neurology, Faculty of Medicine, University of T\u00fcbingen","place":["T\u00fcbingen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasyl","family":"Druchkiv","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]},{"name":"Department of Research and Development, Clinica Baviera-AIER Eye Hospital Group","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansgar","family":"Beuse","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Schultheiss","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Spitzer","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl Ulrich","family":"Bartz-Schmidt","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Clinica Baviera-AIER Eye Hospital Group","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Grohmann","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.ajo.2005.03.038","article-title":"Central retinal artery occlusion: visual outcome","volume":"140","author":"Hayreh","year":"2005","journal-title":"Am J Ophthalmol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/eye.2013.25","article-title":"A review of central retinal artery occlusion: clinical presentation and management","volume":"27","author":"Varma","year":"2013"},{"key":"B3","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.oret.2023.12.007","article-title":"Central retinal artery occlusion: visual outcomes from a large northern california cohort","volume":"8","author":"Shah","year":"2024","journal-title":"Ophthalmol Retina."},{"key":"B4","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/S0014-4835(03)00214-8","article-title":"Central retinal artery occlusion: retinal survival time","volume":"78","author":"Hayreh","year":"2004","journal-title":"Exp Eye Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1161\/STROKEAHA.119.028743","article-title":"Intravenous fibrinolysis for central retinal artery occlusion: a cohort study and updated patient-level meta-analysis","volume":"51","author":"Mac Grory","year":"2020","journal-title":"Stroke."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/17474930241248516","article-title":"Early REperfusion therapy with intravenous alteplase for recovery of vision in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial","author":"Poli","year":"2024","journal-title":"Int J Stroke"},{"key":"B7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1177\/17474930231189352","article-title":"Thrombolysis for central retinal artery occlusion: an individual participant-level meta-analysis","volume":"19","author":"Shahjouei","year":"2024","journal-title":"Int J Stroke."},{"key":"B8","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/S1474-4422(25)00308-4","article-title":"Intravenous alteplase versus oral aspirin for acute central retinal artery occlusion within 4\u00b75 h of severe vision loss (THEIA): a multicentre, double-dummy, patient-blinded and assessor-blinded, randomised, controlled, phase 3 trial","volume":"24","author":"Pr\u00e9terre","year":"2025","journal-title":"Lancet Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1056\/NEJMoa2508515","article-title":"A randomized trial of tenecteplase in acute central retinal artery occlusion","volume":"394","author":"Ryan","year":"2026","journal-title":"N Engl J Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1111\/j.1468-1331.2009.02616.x","article-title":"Central retinal artery occlusion: timing and mode of presentation","volume":"16","author":"Rudkin","year":"2009","journal-title":"Eur J Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fneur.2022.888456","article-title":"Central retinal artery occlusion: current practice, awareness and prehospital delays in Switzerland","volume":"13","author":"Ardila Jurado","year":"2022","journal-title":"Front Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.oret.2023.01.005","article-title":"Central retinal artery occlusion: time to presentation and diagnosis","volume":"7","author":"Shah","year":"2023","journal-title":"Ophthalmol Retina."},{"key":"B13","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.preteyeres.2015.06.001","article-title":"Evidence for an enduring ischaemic penumbra following central retinal artery occlusion, with implications for fibrinolytic therapy","volume":"49","author":"McLeod","year":"2015","journal-title":"Prog Retin Eye Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmed.2023.1129002","article-title":"Central retinal artery occlusion \u2013 detection score","volume":"10","author":"Casagrande","year":"2023","journal-title":"Front Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"45","DOI":"10.2147\/OAEM.S395588","article-title":"The role of ophthalmology in tele-stroke consults for triaging acute vision loss","volume":"16","author":"Artymowicz","year":"2024","journal-title":"Open Access Emerg Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"100630","DOI":"10.1016\/j.xops.2024.100630","article-title":"Automated detection of central retinal artery occlusion using OCT imaging via explainable deep learning","volume":"5","author":"Beuse","year":"2024","journal-title":"Ophthalmol Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.ophtha.2023.11.031","article-title":"A remote consult retinal artery occlusion diagnostic protocol","volume":"131","author":"Lema","year":"2024","journal-title":"Ophthalmology."},{"key":"B18","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1097\/IAE.0b013e3181f2a15c","article-title":"Macular thickness measurements in central retinal artery occlusion by optical coherence tomography","volume":"31","author":"Chen","year":"2011","journal-title":"Retina"},{"key":"B19","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.ajo.2015.01.001","article-title":"Retinal and choroidal changes and visual outcome in central retinal artery occlusion: an optical coherence tomography study","volume":"159","author":"Ahn","year":"","journal-title":"Am J Ophthalmol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/aos.14375","article-title":"Retinal oedema in central retinal artery occlusion develops as a function of time","author":"Ochakovski","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/aos.14563","article-title":"Optical coherence tomography-based determination of ischaemia onset \u2013 the temporal dynamics of retinal thickness increase in acute central retinal artery occlusion","author":"Wenzel","year":"2021","journal-title":"Acta Ophthalmol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"105828","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.105828","article-title":"Structural and functional imaging of the retina in central retinal artery occlusion \u2013 current approaches and future directions","volume":"30","author":"Mac Grory","year":"2021","journal-title":"J Stroke Cerebrovascular Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1097\/IAE.0b013e3182899205","article-title":"In vivo detection of acute ischemic damages in retinal arterial occlusion with optical coherence tomography: a \u201cprominent middle limiting membrane sign","volume":"33","author":"Chu","year":"2013"},{"key":"B24","doi-asserted-by":"publisher","first-page":"9268","DOI":"10.1038\/srep09269","article-title":"Quantitative analysis of retinal layers' optical intensities on 3D optical coherence tomography for central retinal artery occlusion","volume":"18","author":"Chen","year":"2015","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1097\/IAE.0000000000002527","article-title":"Acute retinal ischemia in central versus branch retinal artery occlusion: changes in retinal layers thickness on spectral-domain optical coherence tomography in different grades of retinal ischemia","volume":"40","author":"Matth\u00e9","year":"2020","journal-title":"Retina."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmed.2022.854288","article-title":"Inner retinal layer hyperreflectivity is an early biomarker for acute central retinal artery occlusion","volume":"9","author":"Wenzel","year":"2022","journal-title":"Front Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s40942-025-00770-6","article-title":"Optical coherence tomography findings in acute central retinal artery occlusion and their association with visual outcomes","volume":"12","author":"Wang","year":"2026","journal-title":"Int J Retin Vitr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1177\/1024907920913665","volume":"28","author":"Au SC","year":"2021","journal-title":"Hong Kong J Emerg Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"55272292","DOI":"10.1155\/2021\/5527292","article-title":"Determination of ischemia onset based on automatically generated spectralis SD-OCT values in acute central retinal artery occlusion","volume":"2021","author":"Casagrande","year":"2021","journal-title":"J Ophthalmol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1055\/a-2239-0526","volume":"241","author":"Wiest","year":"2024","journal-title":"Klin Monbl Augenheilkd."},{"key":"B31","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1186\/s12886-023-03176-w","article-title":"Central retinal artery occlusion without cherry-red spots","volume":"23","author":"Fan","year":"2023","journal-title":"BMC Ophthalmol."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000366","article-title":"Management of central retinal artery occlusion","author":"Mac Grory","year":"2021","journal-title":"Stroke"},{"key":"B33","doi-asserted-by":"publisher","first-page":"107895","DOI":"10.1016\/j.jstrokecerebrovasdis.2024.107895","article-title":"Eye stroke protocol in in the emergency department","volume":"33","author":"B\u00e9nard-S\u00e9guin","year":"2024","journal-title":"J Stroke Cerebrovasc Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1097\/IAE.0000000000001017","article-title":"Correlation of optical intensity on optical coherence tomography and visual outcome in central retinal artery occlusion","volume":"36","author":"Chen","year":"2016","journal-title":"Retina."},{"key":"B35","doi-asserted-by":"publisher","first-page":"96777","DOI":"10.5662\/wjm.v15.i2.96777","article-title":"Prognostic factors for acute central retinal artery occlusion treated with hyperbaric oxygen: the Hong Kong study report number five","volume":"15","author":"Au","year":"2025","journal-title":"World J Methodol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1056\/NEJMoa1804355","article-title":"MRI-guided thrombolysis for stroke with unknown time of onset","volume":"379","author":"Thomalla","year":"2018","journal-title":"N Engl J Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"105988","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.105988","article-title":"Acute central retinal artery occlusion seen within 24 hours at a tertiary institution","volume":"30","author":"Chan","year":"2021","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"B38","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1097\/WNO.0000000000001409","article-title":"Referral patterns of central retinal artery occlusion to an academic center affiliated with a stroke center","volume":"41","author":"Flowers","year":"2021","journal-title":"J Neuroophthalmol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2322","DOI":"10.1161\/STROKEAHA.115.009839","article-title":"Retrobulbar spot sign predicts thrombolytic treatment effects and etiology in central retinal artery occlusion","volume":"46","author":"Nedelmann","year":"2015","journal-title":"Stroke."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0247072","article-title":"Transocular sonography in acute arterial occlusions of the eye in elderly patients: diagnostic value of the spot sign","author":"Czihal","year":"2021","journal-title":"PLoS ONE."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10020338","article-title":"The retrobulbar spot sign and prominent middle limiting membrane as prognostic markers in non-arteritic retinal artery occlusion","author":"Schnieder","year":"2021","journal-title":"J Clin Med."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1055\/a-1653-1426","article-title":"Diagnosing Central Retinal Artery Occlusion (CRAO) without fundus examination","author":"Schulthei\u00df","year":"2022","journal-title":"Klin Monbl Augenheilkd."},{"key":"B43","unstructured":"R\n              Core Team\n            \n          \n          Vienna\n          R Foundation for Statistical Computing.\n          R: A Language and Environment for Statistical Computing\n          \n          2021"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1783055\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:33:12Z","timestamp":1778214792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1783055\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":43,"alternative-id":["10.3389\/fneur.2026.1783055"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1783055","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"article-number":"1783055"}}