{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:38:27Z","timestamp":1794008307642,"version":"4.8.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-83473-6","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T20:41:24Z","timestamp":1735591284000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Analysis of the aqueous humor before and after the administration of faricimab in patients with nAMD"],"prefix":"10.1038","volume":"14","author":[{"given":"Ryo","family":"Nonogaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikaru","family":"Ota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyako","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai Fujita","family":"Sajiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahito","family":"Todoroki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji M.","family":"Nishiguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"83473_CR1","doi-asserted-by":"publisher","first-page":"2606","DOI":"10.1056\/NEJMra0801537","volume":"358","author":"RD Jager","year":"2008","unstructured":"Jager, R. D., Mieler, W. F. & Miller, J. W. Age-related Macular Degeneration. N Engl. J. Med. 358, 2606\u20132617 (2008).","journal-title":"N Engl. J. Med."},{"key":"83473_CR2","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/j.ophtha.2009.10.007","volume":"117","author":"R Kawasaki","year":"2010","unstructured":"Kawasaki, R. et al. The prevalence of age-related Macular Degeneration in asians a systematic review and Meta-analysis. Ophthalmology 117, 921\u2013927 (2010).","journal-title":"Ophthalmology"},{"key":"83473_CR3","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s10384-018-0623-4","volume":"63","author":"Y Morizane","year":"2019","unstructured":"Morizane, Y. et al. Incidence and causes of visual impairment in Japan: the first nation-wide complete enumeration survey of newly certified visually impaired individuals. Jpn J. Ophthalmol. 63, 26\u201333 (2019).","journal-title":"Jpn J. Ophthalmol."},{"key":"83473_CR4","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.ophtha.2020.07.060","volume":"128","author":"M Okada","year":"2021","unstructured":"Okada, M. et al. Nonadherence or nonpersistence to Intravitreal Injection Therapy for Neovascular Age-Related Macular Degeneration a mixed-methods systematic review. Ophthalmology 128, 234\u2013247 (2021).","journal-title":"Ophthalmology"},{"key":"83473_CR5","doi-asserted-by":"crossref","unstructured":"Javidi, S. et al. Long-Term Visual Outcomes for a Treat-and-Extend Antivascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration: Up to Seven-Year Follow-Up. J Ophthalmol 1\u201312 (2020). (2020).","DOI":"10.1155\/2020\/3207614"},{"key":"83473_CR6","doi-asserted-by":"publisher","unstructured":"Ota, H. et al. Five-year outcomes of treat and extend regimen using intravitreal aflibercept injection for treatment-na\u00efve age-related macular degeneration. Graefe\u2019s Arch. Clin. Exp. Ophthalmol. 1\u20139. https:\/\/doi.org\/10.1007\/s00417-024-06519-5 (2024).","DOI":"10.1007\/s00417-024-06519-5"},{"key":"83473_CR7","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1189\/jlb.3RI0615-239R","volume":"98","author":"M Chen","year":"2015","unstructured":"Chen, M. & Xu, H. Parainflammation, chronic inflammation, and age-related macular degeneration. J. Leukoc. Biol. 98, 713\u2013725 (2015).","journal-title":"J. Leukoc. Biol."},{"key":"83473_CR8","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1097\/IAE.0000000000000157","volume":"34","author":"T Agawa","year":"2014","unstructured":"Agawa, T. et al. Profile of intraocular immune mediators in patients with age-related macular degeneration and the effect of intravitreal bevacizumab injection. Retin 34, 1811\u20131818 (2014).","journal-title":"Retin"},{"key":"83473_CR9","doi-asserted-by":"publisher","first-page":"471","DOI":"10.3390\/cells8050471","volume":"8","author":"RG Akwii","year":"2019","unstructured":"Akwii, R. G., Sajib, M. S., Zahra, F. T. & Mikelis, C. M. Role of Angiopoietin-2 in vascular physiology and pathophysiology. Cells 8, 471 (2019).","journal-title":"Cells"},{"key":"83473_CR10","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/nrd.2016.278","volume":"16","author":"P Saharinen","year":"2017","unstructured":"Saharinen, P., Eklund, L. & Alitalo, K. Therapeutic targeting of the angiopoietin\u2013TIE pathway. Nat. Rev. Drug Discov. 16, 635\u2013661 (2017).","journal-title":"Nat. Rev. Drug Discov"},{"key":"83473_CR11","doi-asserted-by":"publisher","first-page":"5962","DOI":"10.1038\/ncomms6962","volume":"6","author":"L Hakanpaa","year":"2015","unstructured":"Hakanpaa, L. et al. Endothelial destabilization by angiopoietin-2 via integrin \u03b21 activation. Nat. Commun. 6, 5962 (2015).","journal-title":"Nat. Commun."},{"key":"83473_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/IAE.0000000000003003","volume":"41","author":"JS Heier","year":"2021","unstructured":"Heier, J. S. et al. THE ANGIOPOIETIN\/TIE PATHWAY IN RETINAL VASCULAR DISEASES: a review. Retina 41, 1\u201319 (2021).","journal-title":"Retina"},{"key":"83473_CR13","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1038\/s41433-020-01377-x","volume":"35","author":"AM Joussen","year":"2021","unstructured":"Joussen, A. M. et al. Angiopoietin\/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data. Eye 35, 1305\u20131316 (2021).","journal-title":"Eye"},{"key":"83473_CR14","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.15252\/emmm.201505889","volume":"8","author":"JT Regula","year":"2016","unstructured":"Regula, J. T. et al. Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. Embo Mol. Med. 8, 1265\u20131288 (2016).","journal-title":"Embo Mol. Med."},{"key":"83473_CR15","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/S0140-6736(22)00010-1","volume":"399","author":"JS Heier","year":"2022","unstructured":"Heier, J. S. et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet 399, 729\u2013740 (2022).","journal-title":"Lancet"},{"key":"83473_CR16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1167\/iovs.65.11.15","volume":"65","author":"T Todoroki","year":"2024","unstructured":"Todoroki, T. et al. Aqueous humor cytokine analysis in Age-Related Macular Degeneration after switching from Aflibercept to Faricimab. Investig Ophthalmol. Vis. Sci. 65, 15 (2024).","journal-title":"Investig Ophthalmol. Vis. Sci."},{"key":"83473_CR17","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1007\/s00417-013-2505-2","volume":"252","author":"X Wang","year":"2014","unstructured":"Wang, X. et al. Aqueous vascular endothelial growth factor and ranibizumab concentrations after monthly and bimonthly intravitreal injections of ranibizumab for age-related macular degeneration. Graefe\u2019s Archive Clin. Exp. Ophthalmol. 252, 1033\u20131039 (2014).","journal-title":"Graefe\u2019s Archive Clin. Exp. Ophthalmol."},{"key":"83473_CR18","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1038\/s41598-018-19594-6","volume":"8","author":"T Sato","year":"2018","unstructured":"Sato, T., Takeuchi, M., Karasawa, Y., Enoki, T. & Ito, M. Intraocular inflammatory cytokines in patients with neovascular age-related macular degeneration before and after initiation of intravitreal injection of anti-VEGF inhibitor. Sci. Rep-uk. 8, 1098 (2018).","journal-title":"Sci. Rep-uk"},{"key":"83473_CR19","doi-asserted-by":"publisher","first-page":"5574","DOI":"10.1167\/iovs.15-16418","volume":"56","author":"N Celik","year":"2015","unstructured":"Celik, N., Scheuerle, A., Auffarth, G. U., Kopitz, J. & Dithmar, S. Intraocular pharmacokinetics of Aflibercept and vascular endothelial growth Factor-A. Invest. Opthalmology Vis. Sci. 56, 5574 (2015).","journal-title":"Invest. Opthalmology Vis. Sci."},{"key":"83473_CR20","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.2147\/OPTH.S171636","volume":"12","author":"P Pongsachareonnont","year":"2018","unstructured":"Pongsachareonnont, P., Mak, M. Y. K., Hurst, C. P. & Lam, W. C. Neovascular age-related macular degeneration: intraocular inflammatory cytokines in the poor responder to ranibizumab treatment. Clin. Ophthalmol. Auckl. N Z. 12, 1877\u20131885 (2018).","journal-title":"Clin. Ophthalmol. Auckl. N Z."},{"key":"83473_CR21","doi-asserted-by":"publisher","first-page":"10520","DOI":"10.1038\/s41598-018-28484-w","volume":"8","author":"N Terao","year":"2018","unstructured":"Terao, N. et al. Distinct aqueous humour cytokine profiles of patients with Pachychoroid Neovasculopathy and Neovascular Age-related Macular Degeneration. Sci. Rep-uk. 8, 10520 (2018).","journal-title":"Sci. Rep-uk"},{"key":"83473_CR22","doi-asserted-by":"publisher","first-page":"45081","DOI":"10.1038\/srep45081","volume":"7","author":"DS Ng","year":"2017","unstructured":"Ng, D. S. et al. Elevated angiopoietin 2 in aqueous of patients with neovascular age related macular degeneration correlates with disease severity at presentation. Sci. Rep-uk. 7, 45081 (2017).","journal-title":"Sci. Rep-uk"},{"key":"83473_CR23","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1016\/j.ophtha.2013.01.014","volume":"120","author":"F Abedi","year":"2013","unstructured":"Abedi, F. et al. Genetic influences on the outcome of anti-vascular endothelial growth factor treatment in Neovascular Age-related Macular Degeneration. Ophthalmology 120, 1641\u20131648 (2013).","journal-title":"Ophthalmology"},{"key":"83473_CR24","doi-asserted-by":"publisher","first-page":"e669","DOI":"10.1111\/aos.14970","volume":"100","author":"Z Wang","year":"2022","unstructured":"Wang, Z. et al. Genetic associations of anti-vascular endothelial growth factor therapy response in age\u2010related macular degeneration: a systematic review and meta\u2010analysis. Acta Ophthalmol. 100, e669\u2013e680 (2022).","journal-title":"Acta Ophthalmol."},{"key":"83473_CR25","doi-asserted-by":"publisher","first-page":"594087","DOI":"10.3389\/fphar.2020.594087","volume":"11","author":"I Mantel","year":"2020","unstructured":"Mantel, I. et al. Molecular biomarkers of Neovascular Age-Related Macular Degeneration with Incomplete response to anti-vascular endothelial growth factor treatment. Front. Pharmacol. 11, 594087 (2020).","journal-title":"Front. Pharmacol."},{"key":"83473_CR26","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.2147\/DDDT.S307657","volume":"15","author":"T Sun","year":"2021","unstructured":"Sun, T., Wei, Q., Gao, P., Zhang, Y. & Peng, Q. Cytokine and Chemokine Profile changes in patients with neovascular age-related Macular Degeneration after Intravitreal Ranibizumab Injection for Choroidal Neovascularization. Drug Des. Dev. Ther. 15, 2457\u20132467 (2021).","journal-title":"Drug Des. Dev. Ther."},{"key":"83473_CR27","doi-asserted-by":"publisher","first-page":"7717","DOI":"10.1074\/jbc.270.13.7717","volume":"270","author":"J DiSalvo","year":"1995","unstructured":"DiSalvo, J. et al. Purification and characterization of a naturally occurring vascular endothelial growth factor \u00b7 placenta growth factor heterodimer (\u2217). J. Biol. Chem. 270, 7717\u20137723 (1995).","journal-title":"J. Biol. Chem."},{"key":"83473_CR28","doi-asserted-by":"crossref","unstructured":"Yang, X. et al. Vascular endothelial growth factor-dependent spatiotemporal dual roles of placental growth factor in modulation of angiogenesis and tumor growth. Proc. Natl. Acad. Sci. 110, 13932\u201313937 (2013).","DOI":"10.1073\/pnas.1309629110"},{"key":"83473_CR29","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1177\/1947601911423031","volume":"2","author":"M Shibuya","year":"2011","unstructured":"Shibuya, M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in Angiogenesis. Genes Cancer. 2, 1097\u20131105 (2011).","journal-title":"Genes Cancer"},{"key":"83473_CR30","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s12950-018-0203-x","volume":"15","author":"R Motohashi","year":"2018","unstructured":"Motohashi, R. et al. Dynamics of soluble vascular endothelial growth factor receptors and their ligands in aqueous humour during ranibizumab for age-related macular degeneration. J. Inflamm. 15, 26 (2018).","journal-title":"J. Inflamm."},{"key":"83473_CR31","doi-asserted-by":"publisher","first-page":"e869","DOI":"10.1111\/aos.14691","volume":"99","author":"R Angermann","year":"2021","unstructured":"Angermann, R. et al. Systemic counterregulatory response of angiopoietin-2 after aflibercept therapy for nAMD: a potential escape mechanism. Acta Ophthalmol. 99, e869\u2013e875 (2021).","journal-title":"Acta Ophthalmol."},{"key":"83473_CR32","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.oret.2017.04.004","volume":"2","author":"T Cabral","year":"2018","unstructured":"Cabral, T. et al. Bevacizumab Injection in patients with neovascular age-related Macular Degeneration increases angiogenic biomarkers. Ophthalmol. Retin. 2, 31\u201337 (2018).","journal-title":"Ophthalmol. Retin"},{"key":"83473_CR33","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1167\/tvst.13.11.13","volume":"13","author":"C Diack","year":"2024","unstructured":"Diack, C. et al. Ocular pharmacodynamics of Intravitreal Faricimab in patients with Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema. Transl Vis. Sci. Technol. 13, 13 (2024).","journal-title":"Transl Vis. Sci. Technol."},{"key":"83473_CR34","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s00417-015-3006-2","volume":"254","author":"Y Nomura","year":"2016","unstructured":"Nomura, Y. et al. Effect of posterior vitreous detachment on aqueous humor level of vascular endothelial growth factor in exudative age-related macular degeneration patients. Graefe\u2019s Archive Clin. Exp. Ophthalmol. 254, 53\u201357 (2016).","journal-title":"Graefe\u2019s Archive Clin. Exp. Ophthalmol."},{"key":"83473_CR35","doi-asserted-by":"publisher","first-page":"8747","DOI":"10.1038\/s41598-023-35759-4","volume":"13","author":"R Mukai","year":"2023","unstructured":"Mukai, R. et al. Three-month outcomes of faricimab loading therapy for wet age-related macular degeneration in Japan. Sci. Rep. 13, 8747 (2023).","journal-title":"Sci. Rep."},{"key":"83473_CR36","doi-asserted-by":"publisher","unstructured":"Fukuda, Y. et al. Three-month outcomes of treatment with faricimab or aflibercept for neovascular age-related macular degeneration: a propensity score matching study in a Japanese population. Graefe\u2019s Arch. Clin. Exp. Ophthalmol. 1\u20138. https:\/\/doi.org\/10.1007\/s00417-024-06582-y (2024).","DOI":"10.1007\/s00417-024-06582-y"},{"key":"83473_CR37","doi-asserted-by":"publisher","unstructured":"Matsumoto, H., Hoshino, J., Nakamura, K., Nagashima, T. & Akiyama, H. Short-term outcomes of intravitreal faricimab for treatment-na\u00efve neovascular age-related macular degeneration. Graefe\u2019s Arch. Clin. Exp. Ophthalmol. 1\u20138. https:\/\/doi.org\/10.1007\/s00417-023-06116-y (2023).","DOI":"10.1007\/s00417-023-06116-y"},{"key":"83473_CR38","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.preteyeres.2018.10.006","volume":"69","author":"TV Bergen","year":"2019","unstructured":"Bergen, T. V. et al. The role of placental growth factor (PlGF) and its receptor system in retinal vascular diseases. Prog Retin Eye Res. 69, 116\u2013136 (2019).","journal-title":"Prog Retin Eye Res."},{"key":"83473_CR39","doi-asserted-by":"publisher","first-page":"100954","DOI":"10.1016\/j.preteyeres.2021.100954","volume":"84","author":"A Uemura","year":"2021","unstructured":"Uemura, A. et al. VEGFR1 signaling in retinal angiogenesis and microinflammation. Prog Retin Eye Res. 84, 100954 (2021).","journal-title":"Prog Retin Eye Res."},{"key":"83473_CR40","doi-asserted-by":"publisher","first-page":"4564","DOI":"10.1172\/JCI74527","volume":"124","author":"J Shen","year":"2014","unstructured":"Shen, J. et al. Targeting VE-PTP activates TIE2 and stabilizes the ocular vasculature. J. Clin. Investig. 124, 4564\u20134576 (2014).","journal-title":"J. Clin. Investig"},{"key":"83473_CR41","doi-asserted-by":"publisher","first-page":"e10204","DOI":"10.15252\/emmm.201810204","volume":"11","author":"RH Foxton","year":"2019","unstructured":"Foxton, R. H., Uhles, S., Gr\u00fcner, S., Revelant, F. & Ullmer, C. Efficacy of simultaneous VEGF-A\/ANG\u20102 neutralization in suppressing spontaneous choroidal neovascularization. EMBO Mol. Med. 11, e10204 (2019).","journal-title":"EMBO Mol. Med."},{"key":"83473_CR42","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/j.ajo.2014.01.019","volume":"157","author":"HM Kang","year":"2014","unstructured":"Kang, H. M., Kwon, H. J., Yi, J. H., Lee, C. S. & Lee, S. C. Subfoveal Choroidal Thickness as a potential predictor of visual outcome and treatment response after Intravitreal Ranibizumab injections for typical exudative age-related Macular Degeneration. Am. J. Ophthalmol. 157, 1013\u20131021e1 (2014).","journal-title":"Am. J. Ophthalmol."},{"key":"83473_CR43","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1136\/bjophthalmol-2018-312275","volume":"103","author":"C Hara","year":"2019","unstructured":"Hara, C. et al. Characteristics of patients with neovascular age-related macular degeneration who are non-responders to intravitreal aflibercept. Br. J. Ophthalmol. 103, 623 (2019).","journal-title":"Br. J. Ophthalmol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83473-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83473-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83473-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T15:41:14Z","timestamp":1735659674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83473-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,30]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["83473"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-83473-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,30]]},"assertion":[{"value":"21 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":".","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"31951"}}