{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:30:08Z","timestamp":1792153808843,"version":"4.4.0"},"reference-count":35,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01-EY031315"],"award-info":[{"award-number":["R01-EY031315"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Unrestricted Department Grant"],"award-info":[{"award-number":["Unrestricted Department Grant"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Br J Ophthalmol"],"accepted":{"date-parts":[[2025,7,6]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background\/Aims<\/jats:title>\n                    <jats:p>To assess 24 pro-inflammatory cytokines in the aqueous and serum of normal patients without diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>94 consecutive eyes of 94 patients undergoing elective vitrectomy surgery were prospectively enrolled. Blood and aqueous sampling were done in the operating room. A microparticle bead-based multiplex assay was used to measure aqueous and serum levels of: fibroblast growth factor-2, eotaxin, granulocyte colony stimulating factor (G-CSF), FMS-like tyrosine kinase 3 ligand (FLT-3L), growth-regulated alpha protein (GROa), interleukin (IL)-10, monocyte chemotactic protein (MCP)-3, macrophage-derived chemokine (MDC), soluble CD40L (sCD40L), IL-17A, interleukin-1 receptor antagonist (IL-1RA), IL-1\u03b2, IL-2, IL-4, IL-6, IL-8, interferon gamma-induced protein 10 (IP-10), MCP-1, macrophage inflammatory protein-1\u03b2, tumour necrosis factor-\u03b1, vascular endothelial growth factor (VEGF), regulated on activation normal T expressed and secreted (RANTES), platelet-derived growth factor (PDGF)-AA and PDGF-AB\/BB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A significant positive correlation between aqueous and serum levels was observed for FLT-3L (r=0.45; p&lt;0.001) and positive trends were observed for eotaxin (r=0.27; p=0.04), MDC (r=0.34; p&lt;0.01) and RANTES (r=0.33; p=0.007). There were no significant differences observed based on age or gender. In contrast, aqueous cytokine levels for G-CSF, GROa and MCP-1 were significantly higher in pseudophakic eyes compared with phakic eyes: G-CSF (16.52\u2009pg\/mL\u00b122.39\u2009vs 2.77\u2009pg\/mL\u00b16.80, p\n                      <jats:italic>&lt;<\/jats:italic>\n                      0.0001), GROa (12.45\u2009pg\/mL\u00b16.54\u2009vs 8.26\u2009pg\/mL\u00b15.48, p\n                      <jats:italic>=<\/jats:italic>\n                      0.001) and MCP-1 (1340.51\u2009pg\/mL\u00b1565.21\u2009vs 830.44\u2009pg\/mL\u00b1454.36, p&lt;0.0001), respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We report the first characterisation of 24 different pro-inflammatory cytokines in 94 patients without diabetes. The absence of the crystalline lens was associated with significantly higher aqueous levels of G-CSF, GROa and MCP-1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04505566\">NCT04505566<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bjo-2025-327421","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T17:20:29Z","timestamp":1753204829000},"page":"1357-1362","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of 24 pro-inflammatory cytokines in aqueous and serum of 94 patients without diabetes"],"prefix":"10.1136","volume":"109","clinical-trial-number":[{"clinical-trial-number":"nct04505566","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7861-1563","authenticated-orcid":false,"given":"Stephen Jae","family":"Kim","sequence":"first","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5461-8568","authenticated-orcid":false,"given":"Sapna","family":"Gangaputra","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Sheng","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shriji","family":"Patel","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana A","family":"Nair","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA"},{"name":"Greater Dallas Retina, McKinney, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Al Hussein Al Awamlh","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Fitzpatrick","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA"},{"name":"Austin Retina Associates, Austin, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Cherney","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Veach","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"2025112002101388000_109.12.1357.1","doi-asserted-by":"publisher","DOI":"10.1007\/s13167-023-00314-8"},{"key":"2025112002101388000_109.12.1357.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(95)30973-6"},{"key":"2025112002101388000_109.12.1357.3","first-page":"707","article-title":"Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid","volume":"151","author":"Lutty","year":"1997","journal-title":"Am J Pathol"},{"key":"2025112002101388000_109.12.1357.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2011.05.002"},{"key":"2025112002101388000_109.12.1357.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2006.09.016"},{"key":"2025112002101388000_109.12.1357.6","article-title":"Nonsteroidal anti-inflammatory drugs for retinal disease","volume":"2013","author":"Schoenberger","year":"2013","journal-title":"Int J Inflam"},{"key":"2025112002101388000_109.12.1357.7","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1476fje"},{"key":"2025112002101388000_109.12.1357.8","first-page":"81","article-title":"Activated monocytes and granulocytes, capillary nonperfusion, and neovascularization in diabetic retinopathy","volume":"139","author":"Schr\u00f6der","year":"1991","journal-title":"Am J Pathol"},{"key":"2025112002101388000_109.12.1357.9","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.5.1534"},{"key":"2025112002101388000_109.12.1357.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63952-1"},{"key":"2025112002101388000_109.12.1357.11","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00117-0"},{"key":"2025112002101388000_109.12.1357.12","doi-asserted-by":"crossref","DOI":"10.1016\/j.ophtha.2009.02.030","article-title":"Diabetic Macular Edema","volume":"116","author":"Kim","year":"2009","journal-title":"Ophthalmology"},{"key":"2025112002101388000_109.12.1357.13","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-10410"},{"key":"2025112002101388000_109.12.1357.14","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0b013e3181e095c0"},{"key":"2025112002101388000_109.12.1357.15","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2012.661114"},{"key":"2025112002101388000_109.12.1357.16","first-page":"1005","article-title":"Increased levels of IL-6, sIL-6R, and sgp130 in the aqueous humor and serum of patients with diabetic retinopathy","volume":"22","author":"Chen","year":"2016","journal-title":"Mol Vis"},{"key":"2025112002101388000_109.12.1357.17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2007.02217.x"},{"key":"2025112002101388000_109.12.1357.18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1001\/jamaophthalmol.2013.5692","article-title":"Reduction of vitreous prostaglandin E2 levels after topical administration of ketorolac 0.45%","volume":"132","author":"Schoenberger","year":"2014","journal-title":"JAMA Ophthalmol"},{"key":"2025112002101388000_109.12.1357.19","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2013.6203"},{"key":"2025112002101388000_109.12.1357.20","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0154411","article-title":"The Accuracy of Diagnostic Methods for Diabetic Retinopathy: A Systematic Review and Meta-Analysis","volume":"11","author":"Mart\u00ednez-Vizca\u00edno","year":"2016","journal-title":"PLoS One"},{"key":"2025112002101388000_109.12.1357.21","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1618"},{"key":"2025112002101388000_109.12.1357.22","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6319"},{"key":"2025112002101388000_109.12.1357.23","first-page":"751","article-title":"Critical appraisal of ophthalmic ketorolac in treatment of pain and inflammation following cataract surgery","volume":"5","author":"Reddy","year":"2011","journal-title":"Clin Ophthalmol"},{"key":"2025112002101388000_109.12.1357.24","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.126.9.1203"},{"key":"2025112002101388000_109.12.1357.25","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241713083","article-title":"Macrophage-Derived Chemokine MDC\/CCL22: An Ambiguous Finding in COVID-19","volume":"24","author":"Korobova","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2025112002101388000_109.12.1357.26","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2015.0323"},{"key":"2025112002101388000_109.12.1357.27","doi-asserted-by":"crossref","DOI":"10.1186\/ar4403","article-title":"FMS-related tyrosine kinase 3 ligand (Flt3L)\/CD135 axis in rheumatoid arthritis","volume":"15","author":"Ramos","year":"2013","journal-title":"Arthritis Res Ther"},{"key":"2025112002101388000_109.12.1357.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.07.011"},{"key":"2025112002101388000_109.12.1357.29","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1475"},{"key":"2025112002101388000_109.12.1357.30","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5666"},{"key":"2025112002101388000_109.12.1357.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2006.02.014"},{"key":"2025112002101388000_109.12.1357.32","doi-asserted-by":"crossref","first-page":"371","DOI":"10.3928\/23258160-20190605-05","article-title":"Three-Year Findings on Intraocular Pressure Changes in The Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) Study","volume":"50","author":"Patel","year":"2019","journal-title":"Ophthalmic Surg Lasers Imaging Retina"},{"key":"2025112002101388000_109.12.1357.33","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23208"},{"key":"2025112002101388000_109.12.1357.34","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/imm.13564","article-title":"The immune response as a double-edged sword: The lesson learnt during the COVID-19 pandemic","volume":"167","author":"Agrati","year":"2022","journal-title":"Immunology"},{"key":"2025112002101388000_109.12.1357.35","doi-asserted-by":"crossref","DOI":"10.1186\/s12348-019-0170-2","article-title":"Evaluation of the etiology of persistent iritis after cataract surgery","volume":"9","author":"Neatrour","year":"2019","journal-title":"J Ophthalmic Inflamm Infect"}],"container-title":["British Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bjo-2025-327421","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T09:23:54Z","timestamp":1765704234000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjo.bmj.com\/lookup\/doi\/10.1136\/bjo-2025-327421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,11,20]]},"published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1136\/bjo-2025-327421"],"URL":"https:\/\/doi.org\/10.1136\/bjo-2025-327421","relation":{},"ISSN":["0007-1161","1468-2079"],"issn-type":[{"value":"0007-1161","type":"print"},{"value":"1468-2079","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,22]]}}}