{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:57:55Z","timestamp":1785463075387,"version":"3.56.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"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. Med."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To investigate inner retinal hyperreflectivity on optical coherence tomography (OCT) as a potential biomarker indicating acute central retinal artery occlusion (CRAO).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 56 patients at two university hospitals with acute CRAO (symptom onset \u226448 h) were included in this retrospective study. The optical intensity of the inner retinal layers was determined in both eyes and the relationship between symptom onset and inner retinal layer optical intensity in OCT scans compared to the unaffected fellow eye was analyzed. Several differential diagnoses [central retinal vein occlusion, anterior ischemic optic neuropathy, diabetic macular edema, and subretinal fibrosis\/disciform scar (Junius-Kuhnt)] served as controls to validate optical intensity-based diagnosis of CRAO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CRAO strongly correlated with an increased inner retinal layer hyperreflectivity in this cohort with acute CRAO with a time since symptom onset ranging from 1.1 to 48.0 h. Receiver operating characteristic (ROC) analysis showed an area under the curve of 0.99 to confirm CRAO with a true positive rate of 0.93 and a false positive rate of 0.02. No correlation between optical intensity and time since symptom onset was noticeable. None of the differential diagnoses did show an elevated optical intensity of the inner retinal layers as it was detectable in CRAO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>OCT-based determination of inner retinal layer hyperreflectivity is a very promising biomarker for a prompt diagnosis of CRAO in an emergency setting. This may be of major interest to speed up the administration of a possible thrombolytic treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.854288","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T17:07:17Z","timestamp":1657127237000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Inner Retinal Layer Hyperreflectivity Is an Early Biomarker for Acute Central Retinal Artery Occlusion"],"prefix":"10.3389","volume":"9","author":[{"given":"Daniel A.","family":"Wenzel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Poli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Casagrande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasyl","family":"Druchkiv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Spitzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl Ulrich","family":"Bartz-Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Grohmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Schultheiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","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":"B3","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1111\/ene.14735","article-title":"Central retinal artery occlusion as a neuro-ophthalmological emergency: the need for raising public awareness.","volume":"28","author":"Hoyer","year":"2021","journal-title":"Eur J Neurol."},{"key":"B4","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":"B5","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s00417-008-0989-y","article-title":"Circadian incidence of non-inflammatory retinal artery occlusions.","volume":"247","author":"Schmidt","year":"2009","journal-title":"Graefes Arch Clin Exp Ophthalmol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1001\/jamaneurol.2015.1578","article-title":"Intravenous fibrinolytic therapy in central retinal artery occlusion a patient-level meta-analysis.","volume":"72","author":"Schrag","year":"2015","journal-title":"JAMA Neurol."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198114","article-title":"Intravenous thrombolysis in acute central retinal artery occlusion \u2013 a prospective interventional case series.","volume":"13","author":"Schultheiss","year":"2018","journal-title":"PLoS One."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1080\/02713683.2021.1921219","article-title":"Capturing the occult central retinal artery occlusion using optical coherence tomography.","volume":"46","author":"Balal","year":"2021","journal-title":"Curr Eye Res."},{"key":"B9","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":"2015","journal-title":"Am J Ophthalmol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5527292","article-title":"Determination of ischemia onset based on automatically generatedspectralis SD-OCT values in acute central retinal artery occlusion.","volume":"2021","author":"Casagrande","year":"2021","journal-title":"JOphthalmol."},{"key":"B11","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":"B12","doi-asserted-by":"publisher","first-page":"5209","DOI":"10.1167\/iovs.17-22411","article-title":"Retinal changes in different grades of retinal artery occlusion: an optical coherence tomography study.","volume":"58","author":"Furashova","year":"2017","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.105999","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 Cerebrovasc Dis."},{"key":"B14","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\u2019 thickness on spectral-domain optical coherence tomography in different grades of retinal ischemia.","volume":"40","author":"Matth\u00e9","year":"2020","journal-title":"Retina."},{"key":"B15","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.","volume":"18","author":"Schnieder","year":"2021","journal-title":"J Clin Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e247","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.","volume":"99","author":"Wenzel","year":"2021","journal-title":"Acta Ophthalmol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e680","DOI":"10.1111\/aos.14375","article-title":"Retinal oedema in central retinal artery occlusion develops as a function of time.","volume":"98","author":"Ochakovski","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"B18","first-page":"250","article-title":"Central retinal artery occlusion - findings in optical coherence tomography and functional correlations.","volume":"11","author":"Schmidt","year":"2006","journal-title":"Eur J Med Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep09269","article-title":"Quantitative analysis of retinal layers\u2019 optical intensities on 3D optical coherence tomography for central retinal artery occlusion.","volume":"5","author":"Chen","year":"2015","journal-title":"Sci Rep."},{"key":"B20","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.\u201d.","volume":"33","author":"Chu","year":"2013","journal-title":"Retina."},{"key":"B21","year":"2021","journal-title":"R: A Language and Environment for Statistical Computing. [Internet]."},{"key":"B22","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.","volume":"16","author":"Czihal","year":"2021","journal-title":"PLoS One."},{"key":"B23","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":"B24","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1007\/s00062-020-00955-6","article-title":"Standard diffusion-weighted mri for the diagnosis of central retinal artery occlusion: a case-control study.","volume":"31","author":"Danyel","year":"2021","journal-title":"Clin Neuroradiol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.854288\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T17:07:19Z","timestamp":1657127239000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.854288\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,6]]},"references-count":24,"alternative-id":["10.3389\/fmed.2022.854288"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.854288","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,6]]},"article-number":"854288"}}