{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:11:00Z","timestamp":1793412660299,"version":"4.5.0"},"reference-count":51,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["aaojournal.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ophthalmology"],"published-print":{"date-parts":[[2015,1]]},"DOI":"10.1016\/j.ophtha.2014.07.050","type":"journal-article","created":{"date-parts":[[2014,10,14]],"date-time":"2014-10-14T15:31:27Z","timestamp":1413300687000},"page":"200-210","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":319,"title":["Pathophysiology and Mechanisms of Severe Retinopathy of Prematurity"],"prefix":"10.1016","volume":"122","author":[{"given":"M. Elizabeth","family":"Hartnett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ophtha.2014.07.050_bib1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0002-9394(42)92088-9","article-title":"Extreme prematurity and fibroblastic overgrowth of persistent vascular sheath behind each crystalline lens: (1) preliminary report","volume":"25","author":"Terry","year":"1942","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib2","first-page":"298","article-title":"A\u00a0new ophthalmoscope demonstration","volume":"51","author":"Schepens","year":"1947","journal-title":"Trans Am Acad Ophthalmol Otolaryngol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib3","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1056\/NEJMra1208129","article-title":"Mechanisms and management of retinopathy of prematurity","volume":"367","author":"Hartnett","year":"2012","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.ophtha.2014.07.050_bib4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.earlhumdev.2007.11.009","article-title":"Retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implications for control","volume":"84","author":"Gilbert","year":"2008","journal-title":"Early Hum Dev"},{"key":"10.1016\/j.ophtha.2014.07.050_bib5","doi-asserted-by":"crossref","first-page":"F371","DOI":"10.1136\/fetalneonatal-2011-301121","article-title":"Aggressive posterior retinopathy of prematurity in large preterm babies in South India","volume":"97","author":"Shah","year":"2012","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"10.1016\/j.ophtha.2014.07.050_bib6","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1542\/peds.2006-1088","article-title":"Genetic susceptibility to retinopathy of prematurity","volume":"118","author":"Bizzarro","year":"2006","journal-title":"Pediatrics"},{"key":"10.1016\/j.ophtha.2014.07.050_bib7","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1001\/archopht.123.7.991","article-title":"The International Classification of Retinopathy of Prematurity revisited","volume":"123","year":"2005","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib8","first-page":"96","article-title":"Studies on the pathogenesis of avascular retina and neovascularization into the vitreous in peripheral severe retinopathy of prematurity (an American Ophthalmological Society thesis)","volume":"108","author":"Hartnett","year":"2010","journal-title":"Trans Am Ophthalmol Soc"},{"key":"10.1016\/j.ophtha.2014.07.050_bib9","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1001\/archopht.121.12.1684","article-title":"Revised indications for the treatment of retinopathy of prematurity: results of the Early Treatment for Retinopathy of Prematurity randomized trial","volume":"121","year":"2003","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib10","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1167\/iovs.03-1169","article-title":"Astrocyte-endothelial cell relationships during human retinal vascular development","volume":"45","author":"Chan-Ling","year":"2004","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib11","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.1002\/dvdy.20988","article-title":"The initial fetal human retinal vasculature develops by vasculogenesis","volume":"235","author":"McLeod","year":"2006","journal-title":"Dev Dyn"},{"key":"10.1016\/j.ophtha.2014.07.050_bib12","first-page":"1201","article-title":"The effect of oxygen on\u00a0vasoformative cell division: evidence that \u201cphysiological hypoxia\u201d is\u00a0the stimulus for normal retinal vasculogenesis","volume":"36","author":"Chan-Ling","year":"1995","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib13","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/path.2611","article-title":"M\u00fcller cell-derived VEGF is a significant contributor to retinal neovascularization","volume":"219","author":"Bai","year":"2009","journal-title":"J\u00a0Pathol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib14","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1167\/iovs.13-13755","article-title":"Targeting Muller cell\u2013derived VEGF164 to reduce intravitreal neovascularization in the rat model of retinopathy of prematurity","volume":"55","author":"Jiang","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib15","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1159\/000330174","article-title":"Understanding retinopathy of prematurity: update on pathogenesis","volume":"100","author":"Rivera","year":"2011","journal-title":"Neonatology"},{"key":"10.1016\/j.ophtha.2014.07.050_bib16","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1083\/jcb.200302047","article-title":"VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia","volume":"161","author":"Gerhardt","year":"2003","journal-title":"J\u00a0Cell Biol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib17","first-page":"101","article-title":"Oxygen-induced retinopathy in the mouse","volume":"35","author":"Smith","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib18","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1203\/00006450-199412000-00007","article-title":"Exposure to alternating hypoxia and hyperoxia causes severe proliferative retinopathy in the newborn rat","volume":"36","author":"Penn","year":"1994","journal-title":"Pediatr Res"},{"key":"10.1016\/j.ophtha.2014.07.050_bib19","doi-asserted-by":"crossref","unstructured":"Cunningham S, Fleck BW, Elton RA, Mclntosh N. Transcutaneous oxygen levels in retinopathy of prematurity. Lancet 1995;346:1464-5.","DOI":"10.1016\/S0140-6736(95)92475-2"},{"key":"10.1016\/j.ophtha.2014.07.050_bib20","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/pr.2012.132","article-title":"The relationship between patterns of intermittent hypoxia and retinopathy of\u00a0prematurity in preterm infants","volume":"72","author":"Di Fiore","year":"2012","journal-title":"Pediatr Res"},{"key":"10.1016\/j.ophtha.2014.07.050_bib21","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.ajpath.2013.05.011","article-title":"Short hairpin RNA-mediated knockdown of VEGFA in Muller cells reduces intravitreal neovascularization in a rat model of retinopathy of prematurity","volume":"183","author":"Wang","year":"2013","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib22","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1167\/iovs.13-13429","article-title":"Quantitative analyses of retinal vascular area and density after different methods to reduce VEGF in a rat model of retinopathy of prematurity","volume":"55","author":"Wang","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib23","doi-asserted-by":"crossref","first-page":"4039","DOI":"10.1167\/iovs.10-6798","article-title":"Effect of VEGF Trap on normal retinal vascular development and oxygen-induced retinopathy in the dog","volume":"52","author":"Lutty","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib24","first-page":"840","article-title":"Inhibition of NAD(P)H oxidase reduces apoptosis and avascular retina in an animal model of retinopathy of prematurity","volume":"13","author":"Saito","year":"2007","journal-title":"Mol Vis [serial online]"},{"key":"10.1016\/j.ophtha.2014.07.050_bib25","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1023\/A:1022474120512","article-title":"Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity","volume":"22","author":"Niesman","year":"1997","journal-title":"Neurochem Res"},{"key":"10.1016\/j.ophtha.2014.07.050_bib26","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0161-6420(93)31665-9","article-title":"Prognostic factors in the natural course of retinopathy of prematurity","volume":"100","author":"Schaffer","year":"1993","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ophtha.2014.07.050_bib27","doi-asserted-by":"crossref","first-page":"19898","DOI":"10.1073\/pnas.0805817105","article-title":"Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy","volume":"105","author":"Sears","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ophtha.2014.07.050_bib28","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1001\/jamaophthalmol.2013.986","article-title":"Signaling pathways triggered by oxidative stress that mediate features of severe retinopathy of prematurity","volume":"131","author":"Wang","year":"2013","journal-title":"JAMA Ophthalmol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib29","first-page":"231","article-title":"Endothelial NADPH oxidase 4 mediates vascular endothelial growth factor receptor 2-induced intravitreal neovascularization in a rat model of retinopathy of prematurity","volume":"20","author":"Wang","year":"2014","journal-title":"Mol Vis [serial online]"},{"key":"10.1016\/j.ophtha.2014.07.050_bib30","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.ajpath.2011.11.031","article-title":"VEGF-mediated STAT3 activation inhibits retinal vascularization by down-regulating local erythropoietin expression","volume":"180","author":"Wang","year":"2012","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib31","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1167\/iovs.08-3256","article-title":"The role of supplemental oxygen and JAK\/STAT signaling in intravitreous neovascularization in a ROP rat model","volume":"50","author":"Byfield","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib32","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3109\/02713689608995831","article-title":"The effect of postnatal growth retardation on abnormal neovascularization in the oxygen exposed neonatal rat","volume":"15","author":"Holmes","year":"1996","journal-title":"Curr Eye Res"},{"key":"10.1016\/j.ophtha.2014.07.050_bib33","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1016\/S0140-6736(13)60178-6","article-title":"Retinopathy of prematurity","volume":"382","author":"Hellstr\u00f6m","year":"2013","journal-title":"Lancet"},{"key":"10.1016\/j.ophtha.2014.07.050_bib34","doi-asserted-by":"crossref","unstructured":"Hartnett ME, Morrison MA, Smith S, et al. Genetic variants associated with severe retinopathy of prematurity in extremely low birth weight infants. Invest Ophthalmol Vis Sci 2014 Aug 12. pii: IOVS-14-14841. doi: 10.1167\/iovs.14-14841.","DOI":"10.1167\/iovs.14-14841"},{"key":"10.1016\/j.ophtha.2014.07.050_bib35","first-page":"512","article-title":"VEGF isoforms and their expression after a single episode of hypoxia or repeated fluctuations between hyperoxia and hypoxia: relevance to clinical ROP","volume":"10","author":"McColm","year":"2004","journal-title":"Mol Vis [serial online]"},{"key":"10.1016\/j.ophtha.2014.07.050_bib36","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.exer.2009.06.011","article-title":"Reduction in endothelial tip cell filopodia corresponds to reduced intravitreous but not intraretinal vascularization in a model of ROP","volume":"89","author":"Budd","year":"2009","journal-title":"Exp Eye Res"},{"key":"10.1016\/j.ophtha.2014.07.050_bib37","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood-2006-07-037952","article-title":"Orientation of endothelial cell division is regulated by VEGF signaling during blood vessel formation","volume":"109","author":"Zeng","year":"2007","journal-title":"Blood"},{"key":"10.1016\/j.ophtha.2014.07.050_bib38","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1167\/iovs.08-1780","article-title":"Neutralizing VEGF decreases tortuosity and alters endothelial cell division orientation in arterioles and veins in a rat model of ROP: relevance to plus disease","volume":"49","author":"Hartnett","year":"2008","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib39","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1056\/NEJMoa1007374","article-title":"BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity","volume":"364","author":"Mintz-Hittner","year":"2011","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.ophtha.2014.07.050_bib40","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/archophthalmol.2011.1802","article-title":"Significant treatment failure with intravitreous bevacizumab for retinopathy of prematurity","volume":"130","author":"Patel","year":"2012","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib41","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1167\/iovs.13-11625","article-title":"Anti-VEGF antibody leads to later atypical intravitreous neovascularization and activation of angiogenic pathways in a rat model of retinopathy of prematurity","volume":"54","author":"McCloskey","year":"2013","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib42","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1167\/iovs.05-1570","article-title":"Targeted transgene expression in Muller glia of normal and diseased retinas using lentiviral vectors","volume":"48","author":"Greenberg","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib43","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1167\/iovs.13-13397","article-title":"Effects of anti-VEGF treatment on the recovery of the developing retina following oxygen-induced retinopathy","volume":"55","author":"Tokunaga","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib44","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1542\/peds.2012-2996","article-title":"Screening examination of premature infants for retinopathy of prematurity","volume":"131","year":"2013","journal-title":"Pediatrics"},{"key":"10.1016\/j.ophtha.2014.07.050_bib45","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1167\/iovs.08-2521","article-title":"Suppression of retinal neovascularization by erythropoietin siRNA in a mouse model of proliferative retinopathy","volume":"50","author":"Chen","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib46","doi-asserted-by":"crossref","first-page":"e119","DOI":"10.1542\/peds.2013-0143","article-title":"A\u00a0randomized, masked, placebo-controlled study of darbepoetin alfa in preterm infants","volume":"132","author":"Ohls","year":"2013","journal-title":"Pediatrics"},{"key":"10.1016\/j.ophtha.2014.07.050_bib47","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/j.ajpath.2013.12.023","article-title":"VEGFA activates erythropoietin receptor and enhances VEGFR2-mediated pathological angiogenesis","volume":"184","author":"Yang","year":"2014","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib48","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1001\/archophthalmol.2010.31","article-title":"Longitudinal postnatal weight measurements for the prediction of retinopathy of prematurity","volume":"128","author":"Wu","year":"2010","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.ophtha.2014.07.050_bib49","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.1167\/iovs.14-14216","article-title":"The role of cytochrome p450 epoxygenases in retinal angiogenesis","volume":"55","author":"Capozzi","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib50","doi-asserted-by":"crossref","first-page":"5423","DOI":"10.1167\/iovs.02-0804","article-title":"Inhibition of retinal neovascularization by intravitreal injection of human rPAI-1 in a rat model of retinopathy of prematurity","volume":"44","author":"Penn","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2014.07.050_bib51","doi-asserted-by":"crossref","first-page":"7728","DOI":"10.1167\/iovs.12-11199","article-title":"Author response: different efficacy of propranolol in mice with oxygen-induced retinopathy: could differential effects of propranolol be related to differences in mouse strains [letter]?","volume":"53","author":"Chen","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"}],"container-title":["Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161642014006940?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161642014006940?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T14:05:15Z","timestamp":1758981915000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0161642014006940"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["S0161642014006940"],"URL":"https:\/\/doi.org\/10.1016\/j.ophtha.2014.07.050","relation":{},"ISSN":["0161-6420"],"issn-type":[{"value":"0161-6420","type":"print"}],"subject":[],"published":{"date-parts":[[2015,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pathophysiology and Mechanisms of Severe Retinopathy of Prematurity","name":"articletitle","label":"Article Title"},{"value":"Ophthalmology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ophtha.2014.07.050","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}