{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:52:40Z","timestamp":1791985960215,"version":"4.4.0"},"reference-count":46,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"12","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2026,10,14]]},"DOI":"10.1167\/iovs.67.12.23","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:30:49Z","timestamp":1791984649000},"page":"23","source":"Crossref","is-referenced-by-count":0,"title":["Cross-Sectional Profiling of Aqueous Humor VEGF-A Reflects the Tumor and Ocular Microenvironment in Retinoblastoma"],"prefix":"10.1167","volume":"67","author":[{"given":"Michelle","family":"Lin","sequence":"first","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"},{"name":"USC Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Ching","family":"Peng","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"},{"name":"USC Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Reid","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Huang","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"},{"name":"USC Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Goni","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"},{"name":"USC Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Phung","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"},{"name":"USC Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Chen","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"},{"name":"USC Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drishti","family":"Pandya","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianne","family":"Brown","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibiana J.","family":"Reiser","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"},{"name":"USC Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachana","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, California, United States"},{"name":"University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse L.","family":"Berry","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"},{"name":"USC Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Xu","sequence":"additional","affiliation":[{"name":"The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, United States"},{"name":"USC Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"6","key":"bib1","doi-asserted-by":"publisher","first-page":"778","DOI":"10.4103\/IJO.IJO_2414_23","article-title":"Retinoblastoma - a comprehensive review, update and recent advances","volume":"72","author":"Nag","year":"2024","journal-title":"Indian J Ophthalmol"},{"issue":"12","key":"bib2","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1016\/S0161-6420(85)34105-2","article-title":"Tumor seeding in ocular fine needle aspiration biopsy","volume":"92","author":"Karcioglu","year":"1985","journal-title":"Ophthalmology"},{"issue":"6","key":"bib3","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1111\/j.1755-3768.2009.01637.x","article-title":"Fine-needle aspiration biopsy and other biopsies in suspected intraocular malignant disease: a review","volume":"87","author":"Eide","year":"2009","journal-title":"Acta Ophthalmol"},{"issue":"3","key":"bib4","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1097\/00004397-199303330-00012","article-title":"Fine-needle aspiration biopsy of suspected intraocular tumors","volume":"33","author":"Shields","year":"1993","journal-title":"Int Ophthalmol Clin"},{"issue":"1","key":"bib5","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/1097-0142(19840701)54:1<73::AID-CNCR2820540116>3.0.CO;2-2","article-title":"Effects of fine-needle aspiration and other biopsy procedures on tumor dissemination in mice","volume":"54","author":"Eriksson","year":"1984","journal-title":"Cancer"},{"issue":"8","key":"bib6","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1136\/bjophthalmol-2011-301016","article-title":"Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track","volume":"96","author":"Munier","year":"2012","journal-title":"Br J Ophthalmol"},{"issue":"12","key":"bib7","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1001\/jamaophthalmol.2017.4600","article-title":"Risk of extraocular extension in eyes with retinoblastoma receiving intravitreous chemotherapy","volume":"135","author":"Francis","year":"2017","journal-title":"JAMA Ophthalmol"},{"issue":"175","key":"bib8","first-page":"62939","article-title":"Aqueous humor as a liquid biopsy for retinoblastoma: clear corneal paracentesis and genomic analysis","author":"Kim","year":"2021","journal-title":"J Vis Exp"},{"issue":"11","key":"bib9","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1001\/jamaophthalmol.2017.4097","article-title":"Potential of aqueous humor as a surrogate tumor biopsy for retinoblastoma","volume":"135","author":"Berry","year":"2017","journal-title":"JAMA Ophthalmol"},{"issue":"6","key":"bib10","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.3390\/cancers13061282","article-title":"Establishing the clinical utility of ctDNA analysis for diagnosis, prognosis, and treatment monitoring of retinoblastoma: the aqueous humor liquid biopsy","volume":"13","author":"Xu","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"8","key":"bib11","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1158\/1541-7786.MCR-19-1262","article-title":"Chromosome 6p amplification in aqueous humor cell-free DNA is a prognostic biomarker for retinoblastoma ocular survival","volume":"18","author":"Xu","year":"2020","journal-title":"Mol Cancer Res"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.ajo.2023.11.020","article-title":"Aqueous humor liquid biopsy as a companion diagnostic for retinoblastoma: implications for diagnosis, prognosis, and therapeutic options: five years of progress","volume":"263","author":"Berry","year":"2024","journal-title":"Am J Ophthalmol"},{"issue":"2","key":"bib13","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1167\/tvst.8.2.13","article-title":"Aqueous humor markers in retinoblastoma, a review","volume":"8","author":"Ghiam","year":"2019","journal-title":"Transl Vis Sci Technol"},{"issue":"5","key":"bib14","doi-asserted-by":"publisher","first-page":"e0177337","DOI":"10.1371\/journal.pone.0177337","article-title":"Analysis of aqueous humor concentrations of cytokines in retinoblastoma","volume":"12","author":"Cheng","year":"2017","journal-title":"PLoS One"},{"issue":"3","key":"bib15","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1080\/08820530500350787","article-title":"Anti-angiogenic therapy: prospects for treatment of ocular tumors","volume":"21","author":"Rosenblatt","year":"2006","journal-title":"Semin Ophthalmol"},{"issue":"3","key":"bib16","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/S0092-8674(00)80108-7","article-title":"Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis","volume":"86","author":"Hanahan","year":"1996","journal-title":"Cell"},{"issue":"6","key":"bib17","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/s41573-023-00671-z","article-title":"Targeting angiogenesis in oncology, ophthalmology and beyond","volume":"22","author":"Cao","year":"2023","journal-title":"Nat Rev Drug Discov"},{"issue":"5","key":"bib18","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1136\/jcp.2003.012963","article-title":"Expression of vascular endothelial growth factor, hypoxia inducible factor 1alpha, and carbonic anhydrase IX in human tumours","volume":"57","author":"Jubb","year":"2004","journal-title":"J Clin Pathol"},{"issue":"23","key":"bib19","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1056\/NEJMoa032691","article-title":"Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer","volume":"350","author":"Hurwitz","year":"2004","journal-title":"N Engl J Med"},{"issue":"2","key":"bib20","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.bbrc.2005.05.132","article-title":"Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy","volume":"333","author":"Ferrara","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"issue":"24","key":"bib21","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1056\/NEJMoa061884","article-title":"Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer","volume":"355","author":"Sandler","year":"2006","journal-title":"N Engl J Med"},{"issue":"9605","key":"bib22","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1016\/S0140-6736(07)61904-7","article-title":"Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial","volume":"370","author":"Escudier","year":"2007","journal-title":"Lancet"},{"issue":"13","key":"bib23","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1200\/JCO.2009.26.7849","article-title":"Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival","volume":"28","author":"Escudier","year":"2010","journal-title":"J Clin Oncol"},{"issue":"7","key":"bib24","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1158\/1078-0432.CCR-20-3407","article-title":"FDA approval summary: atezolizumab plus bevacizumab for the treatment of patients with advanced unresectable or metastatic hepatocellular carcinoma","volume":"27","author":"Casak","year":"2021","journal-title":"Clin Cancer Res"},{"issue":"32","key":"bib25","doi-asserted-by":"publisher","first-page":"4945","DOI":"10.1200\/JCO.22.02772","article-title":"Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma","volume":"41","author":"Friedman","year":"2023","journal-title":"J Clin Oncol"},{"issue":"26","key":"bib26","doi-asserted-by":"publisher","first-page":"2484","DOI":"10.1056\/NEJMoa1103799","article-title":"A phase 3 trial of bevacizumab in ovarian cancer","volume":"365","author":"Perren","year":"2011","journal-title":"N Engl J Med"},{"issue":"26","key":"bib27","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1056\/NEJMoa1104390","article-title":"Incorporation of bevacizumab in the primary treatment of ovarian cancer","volume":"365","author":"Burger","year":"2011","journal-title":"N Engl J Med"},{"issue":"10103","key":"bib28","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1016\/S0140-6736(17)31607-0","article-title":"Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240)","volume":"390","author":"Tewari","year":"2017","journal-title":"Lancet"},{"issue":"10S","key":"bib29","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1016\/j.ophtha.2016.04.056","article-title":"Anti-vascular endothelial growth factor agents in the treatment of retinal disease: from bench to bedside","volume":"123","author":"Campochiaro","year":"2016","journal-title":"Ophthalmology"},{"issue":"5","key":"bib30","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1006\/exer.1996.0141","article-title":"Expression of vascular endothelial growth factor (VEGF) in retinoblastoma but not in posterior uveal melanoma","volume":"63","author":"Kvanta","year":"1996","journal-title":"Exp Eye Res"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1186\/1471-2407-10-504","article-title":"Irresponsiveness of two retinoblastoma cases to conservative therapy correlates with up- regulation of hERG1 channels and of the VEGF-A pathway","volume":"10","author":"Fortunato","year":"2010","journal-title":"BMC Cancer"},{"issue":"2","key":"bib32","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S0002-9440(10)63129-X","article-title":"Higher vessel densities in retinoblastoma with local invasive growth and metastasis","volume":"164","author":"R\u00f6ssler","year":"2004","journal-title":"Am J Pathol"},{"issue":"10","key":"bib33","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1136\/bjo.87.10.1224","article-title":"Tumour angiogenesis as a prognostic factor for disease dissemination in retinoblastoma","volume":"87","author":"Marback","year":"2003","journal-title":"Br J Ophthalmol"},{"issue":"2","key":"bib34","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1021\/acs.jproteome.3c00756","article-title":"Liquid biopsy proteomics in ophthalmology","volume":"23","author":"Wolf","year":"2024","journal-title":"J Proteome Res"},{"issue":"1","key":"bib35","doi-asserted-by":"publisher","first-page":"e000073","DOI":"10.1136\/bmjonc-2023-000073","article-title":"Novel proteomics-based plasma test for early detection of multiple cancers in the general population","volume":"3","author":"Budnik","year":"2024","journal-title":"BMJ Oncol"},{"issue":"6","key":"bib36","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1167\/iovs.65.6.18","article-title":"Aqueous VEGF-A levels as a liquid biopsy biomarker of retinoblastoma vitreous seed response to therapy","volume":"65","author":"Daniels","year":"2024","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.ophtha.2025.03.018","article-title":"Safety assessment of aqueous humor liquid biopsy in retinoblastoma: a multicenter study of 1203 procedures","volume":"133","author":"Chigane","year":"2026","journal-title":"Ophthalmology"},{"issue":"4","key":"bib38","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1002\/pbc.24303","article-title":"Long-term outcomes of group D eyes in bilateral retinoblastoma patients treated with chemoreduction and low-dose IMRT salvage","volume":"60","author":"Berry","year":"2013","journal-title":"Pediatr Blood Cancer"},{"issue":"12","key":"bib39","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1016\/j.ophtha.2017.05.034","article-title":"Not all seeds are created equal: seed classification is predictive of outcomes in retinoblastoma","volume":"124","author":"Berry","year":"2017","journal-title":"Ophthalmology"},{"issue":"4","key":"bib40","doi-asserted-by":"publisher","first-page":"26270","DOI":"10.1002\/pbc.26270","article-title":"Risk of metastasis and orbital recurrence in advanced retinoblastoma eyes treated with systemic chemoreduction versus primary enucleation","volume":"64","author":"Berry","year":"2017","journal-title":"Pediatr Blood Cancer"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"889647","DOI":"10.3389\/fneur.2022.889647","article-title":"Technical performance evaluation of Olink proximity extension assay for blood-based biomarker discovery in longitudinal studies of Alzheimer's disease","volume":"13","author":"Carlyle","year":"2022","journal-title":"Front Neurol"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"100168","DOI":"10.1016\/j.mcpro.2021.100168","article-title":"Proximity extension assay in combination with next-generation sequencing for high-throughput proteome-wide analysis","volume":"20","author":"Wik","year":"2021","journal-title":"Mol Cell Proteomics"},{"issue":"3","key":"bib43","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1136\/bjo.63.3.161","article-title":"Postinflammatory and malignant protein patterns in aqueous humour","volume":"63","author":"Dias","year":"1979","journal-title":"Br J Ophthalmol"},{"issue":"1","key":"bib44","doi-asserted-by":"publisher","first-page":"e8","DOI":"10.1111\/j.1442-9071.2011.02711.x","article-title":"Analysis of aqueous humour proteins in patients with retinoblastoma","volume":"40","author":"Hadjistilianou","year":"2012","journal-title":"Clin Exp Ophthalmol"},{"issue":"12","key":"bib45","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.5858\/arpa.2014-0262-OA","article-title":"Expression of angiogenic factors in invasive retinoblastoma tumors is associated with increase in tumor cells expressing stem cell marker Sox2","volume":"139","author":"Garcia","year":"2015","journal-title":"Arch Pathol Lab Med"},{"issue":"8","key":"bib46","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1016\/S0161-6420(97)30150-X","article-title":"Rubeosis iridis in retinoblastoma. Histologic findings and the possible role of vascular endothelial growth factor in its induction","volume":"104","author":"Pe'er","year":"1997","journal-title":"Ophthalmology"}],"container-title":["Investigative Ophthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.12.23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:30:50Z","timestamp":1791984650000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.12.23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":46,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.67.12.23","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10,14]]}}}