{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T22:38:49Z","timestamp":1778539129035,"version":"3.51.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["092668\/Z\/10\/Z"],"award-info":[{"award-number":["092668\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01AI034969"],"award-info":[{"award-number":["5R01AI034969"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling, and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used retinal angiography to study blood-retinal barrier integrity. We analyzed retinal leakage, histopathology, brain magnatic resonance imaging (MRI), and associations with death and neurological disability in prospective cohorts of Malawian children with cerebral malaria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Three types of retinal leakage were seen: large focal leak (LFL), punctate leak (PL), and vessel leak. The LFL and PL were associated with death (odds ratio [OR] = 13.20, 95% confidence interval [CI] = 5.21\u201333.78 and OR = 8.58, 95% CI = 2.56\u201329.08, respectively) and brain swelling (P\u2005&amp;lt;\u2005.05). Vessel leak and macular nonperfusion were associated with neurological disability (OR = 3.71, 95% CI = 1.26\u201311.02 and OR = 9.06, 95% CI = 1.79\u201345.90). Large focal leak was observed as an evolving retinal hemorrhage. A core of fibrinogen and monocytes was found in 39 (93%) white-centered hemorrhages.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Blood-retina barrier breakdown occurs in 3 patterns in cerebral malaria. Associations between LFL, brain swelling, and death suggest that the rapid accumulation of cerebral hemorrhages, with accompanying fluid egress, may cause fatal brain swelling. Vessel leak, from barrier dysfunction, and nonperfusion were not associated with severe brain swelling but with neurological deficits, suggesting hypoxic injury in survivors.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaa541","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T11:07:43Z","timestamp":1598267263000},"page":"1070-1080","source":"Crossref","is-referenced-by-count":23,"title":["How Does Blood-Retinal Barrier Breakdown Relate to Death and Disability in Pediatric Cerebral Malaria?"],"prefix":"10.1093","volume":"225","author":[{"given":"Ian J C","family":"MacCormick","sequence":"first","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, a Member of Liverpool Health Partners, Liverpool, United Kingdom"},{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi"},{"name":"Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Barrera","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, a Member of Liverpool Health Partners, Liverpool, United Kingdom"},{"name":"NHS Blood and Transplant, Tissue and Eye Services R&D, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8086-990X","authenticated-orcid":false,"given":"Nicholas A V","family":"Beare","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, a Member of Liverpool Health Partners, Liverpool, United Kingdom"},{"name":"St. Paul\u2019s Eye Unit, Liverpool University Hospitals Foundation Trust, Liverpool, United 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Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S","family":"Heyderman","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi"},{"name":"Division of Infection and Immunity, University College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alister G","family":"Craig","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm E","family":"Molyneux","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi"},{"name":"Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Macpherson","family":"Mallewa","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Queen Elizabeth Central Hospital, Blantyre, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie A","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Milner","sequence":"additional","affiliation":[{"name":"American Society for Clinical Pathology, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Hiscott","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, a Member of Liverpool Health Partners, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terrie E","family":"Taylor","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"},{"name":"Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl B","family":"Seydel","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"},{"name":"Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon P","family":"Harding","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, 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