{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:56:20Z","timestamp":1791608180898,"version":"4.3.4"},"reference-count":25,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ophthalmologyscience.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ophthalmology Science"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.xops.2025.100781","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T05:45:34Z","timestamp":1743486334000},"page":"100781","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["HORNBILL: A First-in-Human Phase I\/IIa Study of the Safety, Tolerability, and Early Pharmacodynamics of BI 764524 for Diabetic Macular Ischemia"],"prefix":"10.1016","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6024-8441","authenticated-orcid":false,"given":"Quan Dong","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chirag","family":"Jhaveri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maged","family":"Habib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasir J.","family":"Sepah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Nassar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartlomiej","family":"Krawczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Simons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Giani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Pearce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Gliem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sobha","family":"Sivaprasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.xops.2025.100781_bib1","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.ophtha.2021.04.027","article-title":"Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis","volume":"128","author":"Teo","year":"2021","journal-title":"Ophthalmology"},{"key":"10.1016\/j.xops.2025.100781_bib2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s13167-023-00314-8","article-title":"Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications-risks and mitigation","volume":"14","author":"Kropp","year":"2023","journal-title":"EPMA J"},{"key":"10.1016\/j.xops.2025.100781_bib3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/s41433-021-01649-0","article-title":"Retinal non-perfusion in diabetic retinopathy","volume":"36","author":"Wykoff","year":"2022","journal-title":"Eye (Lond)"},{"key":"10.1016\/j.xops.2025.100781_bib4","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1038\/s41433-024-02981-x","article-title":"Retinal non-perfusion: recognizing and defining what is important","volume":"38","author":"Cao","year":"2024","journal-title":"Eye (Lond)"},{"key":"10.1016\/j.xops.2025.100781_bib5","article-title":"Peripheral and central capillary non-perfusion in diabetic retinopathy: an updated overview","volume":"10","author":"Antropoli","year":"2023","journal-title":"Front Med (Lausanne)"},{"key":"10.1016\/j.xops.2025.100781_bib6","article-title":"An overview of our current understanding of diabetic macular ischemia (DMI)","volume":"10","author":"Usman","year":"2018","journal-title":"Cureus"},{"key":"10.1016\/j.xops.2025.100781_bib7","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1001\/jamaophthalmol.2022.0135","article-title":"Why is continued vision loss still a problem in some patients with diabetic retinopathy, despite treatment?","volume":"140","author":"Bressler","year":"2022","journal-title":"JAMA Ophthalmol"},{"key":"10.1016\/j.xops.2025.100781_bib8","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1159\/000515406","article-title":"Looking ahead: visual and anatomical endpoints in future trials of diabetic macular ischemia","volume":"244","author":"Cheung","year":"2021","journal-title":"Ophthalmologica"},{"key":"10.1016\/j.xops.2025.100781_bib9","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1167\/iovs.12-11103","article-title":"The effects of macular ischemia on visual acuity in diabetic retinopathy","volume":"54","author":"Sim","year":"2013","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.xops.2025.100781_bib10","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.oret.2022.07.010","article-title":"Characterization of the structural and functional alteration in eyes with diabetic macular ischemia","volume":"7","author":"Tsai","year":"2023","journal-title":"Ophthalmol Retina"},{"key":"10.1016\/j.xops.2025.100781_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.preteyeres.2021.101033","article-title":"Diabetic macular ischaemia- a new therapeutic target?","volume":"89","author":"Cheung","year":"2022","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.xops.2025.100781_bib12","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.2147\/OPTH.S272328","article-title":"Macular vessel density in diabetic retinopathy patients: how can we accurately measure and what can it tell us?","volume":"15","author":"Pramil","year":"2021","journal-title":"Clin Ophthalmol"},{"key":"10.1016\/j.xops.2025.100781_bib13","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.oret.2022.05.028","article-title":"Deep capillary geometric perfusion deficits on OCT angiography detect clinically referable eyes with diabetic retinopathy","volume":"6","author":"Nesper","year":"2022","journal-title":"Ophthalmol Retina"},{"key":"10.1016\/j.xops.2025.100781_bib14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-6448-2_1","article-title":"Semaphorins and their signaling mechanisms","volume":"1493","author":"Alto","year":"2017","journal-title":"Methods Mol Biol"},{"key":"10.1016\/j.xops.2025.100781_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.jcjd.2012.07.380","article-title":"The guidance protein semaphorin3A provokes vascular leakage in diabetic retinopathy","volume":"36","author":"Cerani","year":"2012","journal-title":"Can J Diabetes"},{"key":"10.1016\/j.xops.2025.100781_bib16","doi-asserted-by":"crossref","first-page":"6024","DOI":"10.1182\/blood-2010-10-311589","article-title":"Ischemic neurons prevent vascular regeneration of neural tissue by secreting semaphorin 3A","volume":"117","author":"Joyal","year":"2011","journal-title":"Blood"},{"key":"10.1016\/j.xops.2025.100781_bib17","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.preteyeres.2016.02.003","article-title":"NRP1 function and targeting in neurovascular development and eye disease","volume":"52","author":"Raimondi","year":"2016","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.xops.2025.100781_bib18","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.1172\/JCI76492","article-title":"Neuropilin-1 mediates myeloid cell chemoattraction and influences retinal neuroimmune crosstalk","volume":"124","author":"Dejda","year":"2014","journal-title":"J Clin Invest"},{"key":"10.1016\/j.xops.2025.100781_bib19","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1167\/iovs.16-19468","article-title":"Association of plasma semaphorin 3A with phenotypes of diabetic retinopathy and nephropathy","volume":"57","author":"Kwon","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.xops.2025.100781_bib20","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ophtha.2016.10.008","article-title":"Quantification of diabetic macular ischemia using optical coherence tomography angiography and its relationship with visual acuity","volume":"124","author":"Samara","year":"2017","journal-title":"Ophthalmology"},{"key":"10.1016\/j.xops.2025.100781_bib21","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.oret.2017.03.003","article-title":"Phase I trial of anti-vascular endothelial growth factor\/anti-angiopoietin 2 bispecific antibody RG7716 for neovascular age-related macular degeneration","volume":"1","author":"Chakravarthy","year":"2017","journal-title":"Ophthalmol Retina"},{"key":"10.1016\/j.xops.2025.100781_bib22","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1167\/iovs.62.1.9","article-title":"Diabetic macular ischemia: influence of optical coherence tomography angiography parameters on changes in functional outcomes over one year","volume":"62","author":"Tsai","year":"2021","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.xops.2025.100781_bib23","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ajo.2024.09.012","article-title":"A comparison of optical coherence tomography angiography metrics and artifacts on scans of different sizes in diabetic macular ischemia","volume":"269","author":"Tsai","year":"2024","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.xops.2025.100781_bib24","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/IAE.0000000000001951","article-title":"Comparison of 3 mm \u00d7 3 mm versus 6 mm \u00d7 6 mm optical coherence tomography angiography scan sizes in the evaluation of non-proliferative diabetic retinopathy","volume":"39","author":"Ho","year":"2019","journal-title":"Retina"},{"key":"10.1016\/j.xops.2025.100781_bib25","first-page":"2552","article-title":"The effect of different optical coherence tomography angiography macular scan sizes on foveal avascular zone metrics in patients with diabetic macular ischaemia","volume":"64","author":"Tsai","year":"2023","journal-title":"Invest Ophthalmol Vis Sci"}],"container-title":["Ophthalmology Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S266691452500079X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S266691452500079X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T21:11:00Z","timestamp":1772053860000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S266691452500079X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["S266691452500079X"],"URL":"https:\/\/doi.org\/10.1016\/j.xops.2025.100781","relation":{},"ISSN":["2666-9145"],"issn-type":[{"value":"2666-9145","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"HORNBILL: A First-in-Human Phase I\/IIa Study of the Safety, Tolerability, and Early Pharmacodynamics of BI 764524 for Diabetic Macular Ischemia","name":"articletitle","label":"Article Title"},{"value":"Ophthalmology Science","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xops.2025.100781","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.","name":"copyright","label":"Copyright"}],"article-number":"100781"}}