{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:17:21Z","timestamp":1787505441047,"version":"build-2736575974"},"reference-count":38,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T00:00:00Z","timestamp":1705017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ophthalmologyscience.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ophthalmology Science"],"published-print":{"date-parts":[[2024,7]]},"DOI":"10.1016\/j.xops.2024.100467","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T12:15:01Z","timestamp":1705580101000},"page":"100467","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bispecific VEGF-A and Angiopoietin-2 Antagonist RO-101 Preclinical Efficacy in Model of Neovascular Eye Disease"],"prefix":"10.1016","volume":"4","author":[{"given":"Li","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3836-9095","authenticated-orcid":false,"given":"Jessi R.","family":"Prentice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Velez-Montoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Barakat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwin","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lowenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshad M.","family":"Khanani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter K.","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Heier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua L.","family":"Morgenstern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Strong Caldwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklaus","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Quiroz-Mercado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Huvard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Bhatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramanath","family":"Bhandari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.xops.2024.100467_bib1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00109-013-0993-5","article-title":"Ocular neovascularization","volume":"91","author":"Campochiaro","year":"2013","journal-title":"J\u00a0Mol Med (Berl)"},{"key":"10.1016\/j.xops.2024.100467_bib2","first-page":"1929","article-title":"Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor","volume":"37","author":"Kvanta","year":"1996","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.xops.2024.100467_bib3","first-page":"855","article-title":"Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes","volume":"37","author":"Lopez","year":"1996","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.xops.2024.100467_bib4","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0002-9394(14)75794-0","article-title":"Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy","volume":"118","author":"Adamis","year":"1994","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib5","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1056\/NEJM199412013312203","article-title":"Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders","volume":"331","author":"Aiello","year":"1994","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.xops.2024.100467_bib6","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1001\/archopht.120.3.338","article-title":"Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment","volume":"120","author":"Krzystolik","year":"2002","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib7","first-page":"638","article-title":"Hypoxia-induced expression of vascular endothelial growth factor by retinal cells is a common factor in neovascularizing ocular diseases","volume":"72","author":"Pe\u2019er","year":"1995","journal-title":"Lab Invest"},{"key":"10.1016\/j.xops.2024.100467_bib8","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1001\/archopht.1994.01090230090028","article-title":"Detection of vascular endothelial growth factor messenger RNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy","volume":"112","author":"Malecaze","year":"1994","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib9","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.2353\/ajpath.2006.050588","article-title":"Inhibition of platelet-derived growth factor B signaling enhances the efficacy of anti-vascular endothelial growth factor therapy in multiple models of ocular neovascularization","volume":"168","author":"Jo","year":"2006","journal-title":"Am J Pathol"},{"key":"10.1016\/j.xops.2024.100467_bib10","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1172\/JCI66549","article-title":"Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis","volume":"123","author":"Ziegler","year":"2013","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.xops.2024.100467_bib11","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/jcp.10442","article-title":"Angiopoietin-2 enhances retinal vessel sensitivity to vascular endothelial growth factor","volume":"199","author":"Oshima","year":"2004","journal-title":"J\u00a0Cell Physiol"},{"key":"10.1016\/j.xops.2024.100467_bib12","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1096\/fj.04-2209fje","article-title":"Different effects of angiopoietin-2 in different vascular beds: new vessels are most sensitive","volume":"19","author":"Oshima","year":"2005","journal-title":"FASEB J"},{"key":"10.1016\/j.xops.2024.100467_bib13","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.ajo.2004.10.004","article-title":"Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy","volume":"139","author":"Watanabe","year":"2005","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib14","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1755-3768.2012.02473.x","article-title":"Ang-2 upregulation correlates with increased levels of MMP-9, VEGF, EPO and TGF\u03b21 in diabetic eyes undergoing vitrectomy","volume":"91","author":"Loukovaara","year":"2013","journal-title":"Acta Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib15","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1056\/NEJMoa054481","article-title":"Ranibizumab for neovascular age-related macular degeneration","volume":"355","author":"Rosenfeld","year":"2006","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.xops.2024.100467_bib16","first-page":"361","article-title":"Ranibizumab: phase III clinical trial results","volume":"19","author":"Rosenfeld","year":"2006","journal-title":"Ophthalmol Clin North Am"},{"key":"10.1016\/j.xops.2024.100467_bib17","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1001\/archopht.125.11.1460","article-title":"Improved vision-related function after ranibizumab treatment of neovascular age-related macular degeneration: results of a randomized clinical trial","volume":"125","author":"Chang","year":"2007","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib18","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ophtha.2008.10.018","article-title":"Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the Anchor study","volume":"116","author":"Brown","year":"2009","journal-title":"Ophthalmology"},{"key":"10.1016\/j.xops.2024.100467_bib19","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1136\/bjo.2006.113902","article-title":"Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions","volume":"91","author":"Lux","year":"2007","journal-title":"Br J Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib20","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1097\/IAE.0000000000003441","article-title":"Intravitreal nesvacumab (antiangiopoietin 2) plus aflibercept in diabetic macular edema: phase 2 RUBY randomized trial","volume":"42","author":"Brown","year":"2022","journal-title":"Retina"},{"key":"10.1016\/j.xops.2024.100467_bib21","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF02133684","article-title":"Optimized protocol for Fluorotron Master","volume":"222","author":"Gray","year":"1985","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib22","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1080\/09273940802710705","article-title":"Intravitreal anakinra inhibits choroidal neovascular membrane growth in a rat model","volume":"17","author":"Olson","year":"2009","journal-title":"Ocul Immunol Inflamm"},{"key":"10.1016\/j.xops.2024.100467_bib23","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.visres.2003.09.027","article-title":"Intravitreal triamcinolone does not alter basal vascular endothelial growth factor mRNA expression in rat retina","volume":"44","author":"Gao","year":"2004","journal-title":"Vision Res"},{"key":"10.1016\/j.xops.2024.100467_bib24","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1006\/exer.2000.0907","article-title":"Quantitative image analysis of laser-induced choroidal neovascularization in rat","volume":"71","author":"Edelman","year":"2000","journal-title":"Exp Eye Res"},{"key":"10.1016\/j.xops.2024.100467_bib25","doi-asserted-by":"crossref","first-page":"10756","DOI":"10.1073\/pnas.0805293105","article-title":"Combinatorial Surrobody libraries","volume":"105","author":"Xu","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.xops.2024.100467_bib26","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1126\/science.2531466","article-title":"Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda","volume":"246","author":"Huse","year":"1989","journal-title":"Science"},{"key":"10.1016\/j.xops.2024.100467_bib27","doi-asserted-by":"crossref","first-page":"8106","DOI":"10.1002\/anie.200603381","article-title":"Manufacturing immunity to disease in a test tube: the magic bullet realized","volume":"45","author":"Lerner","year":"2006","journal-title":"Angew Chem Int Ed Engl"},{"key":"10.1016\/j.xops.2024.100467_bib28","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1167\/iovs.16-19204","article-title":"Intraocular pharmacokinetics of intravitreal aflibercept (Eylea) in a rabbit model","volume":"57","author":"Park","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.xops.2024.100467_bib29","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1016\/j.ophtha.2007.09.012","article-title":"Pharmacokinetics of intravitreal ranibizumab (Lucentis)","volume":"114","author":"Bakri","year":"2007","journal-title":"Ophthalmology"},{"key":"10.1016\/j.xops.2024.100467_bib31","doi-asserted-by":"crossref","first-page":"697","DOI":"10.2147\/OPTH.S19555","article-title":"Pharmacokinetics of intravitreal bevacizumab (Avastin\u00ae) in rabbits","volume":"5","author":"Sinapis","year":"2011","journal-title":"Clin Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib32","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3390\/pharmaceutics11080365","article-title":"Pharmacokinetics of intravitreal anti-VEGF drugs in age-related macular degeneration","volume":"11","author":"Garc\u00eda-Quintanilla","year":"2019","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.xops.2024.100467_bib33","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4274\/tjo.28003","article-title":"Factors affecting compliance to intravitreal anti-vascular endothelial growth factor therapy in patients with age-related macular degeneration","volume":"47","author":"Polat","year":"2017","journal-title":"Turk J Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib34","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1016\/j.ophtha.2016.03.045","article-title":"Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: the comparison of age-related macular degeneration treatments trials","volume":"123","author":"Maguire","year":"2016","journal-title":"Ophthalmology"},{"key":"10.1016\/j.xops.2024.100467_bib35","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1001\/jamaophthalmol.2019.4577","article-title":"Association of visit adherence and visual acuity in patients with neovascular age-related macular degeneration: secondary analysis of the comparison of age-related macular degeneration treatment trial","volume":"138","author":"Ramakrishnan","year":"2020","journal-title":"JAMA Ophthalmol"},{"key":"10.1016\/j.xops.2024.100467_bib36","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.1038\/s41433-023-02553-5","article-title":"The real-world efficacy and safety of faricimab in neovascular age-related macular degeneration: the TRUCKEE study\u22126 month results","volume":"37","author":"Khanani","year":"2023","journal-title":"Eye (Lond)"},{"key":"10.1016\/j.xops.2024.100467_bib37","series-title":"Introductory Chemistry Essentials","author":"Tro","year":"2014"},{"key":"10.1016\/j.xops.2024.100467_bib38","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/j.ophtha.2014.05.009","article-title":"Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration","volume":"121","author":"Ho","year":"2014","journal-title":"Ophthalmology"},{"key":"10.1016\/j.xops.2024.100467_bib39","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.canlet.2012.08.018","article-title":"Angiopoietins in angiogenesis","volume":"328","author":"Fagiani","year":"2013","journal-title":"Cancer Lett"}],"container-title":["Ophthalmology Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666914524000034?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666914524000034?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T11:36:41Z","timestamp":1721043401000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666914524000034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["S2666914524000034"],"URL":"https:\/\/doi.org\/10.1016\/j.xops.2024.100467","relation":{},"ISSN":["2666-9145"],"issn-type":[{"value":"2666-9145","type":"print"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Bispecific VEGF-A and Angiopoietin-2 Antagonist RO-101 Preclinical Efficacy in Model of Neovascular Eye Disease","name":"articletitle","label":"Article Title"},{"value":"Ophthalmology Science","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xops.2024.100467","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 by the American Academy of Ophthalmology.","name":"copyright","label":"Copyright"}],"article-number":"100467"}}