{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:12:48Z","timestamp":1793747568133,"version":"4.6.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K16951"],"award-info":[{"award-number":["18K16951"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Senju"},{"name":"HOYA"},{"DOI":"10.13039\/501100011746","name":"NOVARTIS Foundation (Japan) for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011746","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010793","name":"Pfizer Japan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007816","name":"Alcon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007816","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004286","name":"Santen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004286","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004088","name":"Kowa Life Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004088","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIDEK"},{"DOI":"10.13039\/501100004419","name":"Wakamoto Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004419","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AMO"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intraocular surgery is associated with increased ocular inflammation. If maintained for a prolonged period after surgery, this inflammation can cause various complications, including subconjunctival fibrosis and bleb scarring. This clinical trial was a prospective, randomised, single-blind, interventional study comparing the efficacy and safety of 0.1% bromfenac sodium ophthalmic solution and 0.02% fluorometholone ophthalmic suspension in the inhibition of multiple inflammatory cytokines in the aqueous humour of 26 patients with pseudophakic eyes who had undergone phacoemulsification and intraocular lens implantation. The patients were randomly assigned to one of the trial drugs, and aqueous humour samples were collected before and after drug administration. Platelet-derived growth factor-AA levels significantly decreased in both drug groups, but they were significantly higher in the fluorometholone group than in the bromfenac group (<jats:italic>P<\/jats:italic>\u2009=\u20090.034). Bromfenac also significantly decreased vascular endothelial growth factor level (<jats:italic>P<\/jats:italic>\u2009=\u20090.0077), as well as monocyte chemoattractant protein-1 level (<jats:italic>P<\/jats:italic>\u2009=\u20090.013), which was elevated for a prolonged period after phacoemulsification. These data suggest that bromfenac is useful to alleviate prolonged microenvironmental alterations in the aqueous humour of pseudophakic eyes.<\/jats:p>","DOI":"10.1038\/s41598-021-85495-w","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T11:14:42Z","timestamp":1615893282000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Topical bromfenac reduces multiple inflammatory cytokines in the aqueous humour of pseudophakic patients"],"prefix":"10.1038","volume":"11","author":[{"given":"Takehiro","family":"Matsumura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Arimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Takamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Inatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"85495_CR1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1136\/bjo.78.2.91","volume":"78","author":"SM Shah","year":"1994","unstructured":"Shah, S. M. & Spalton, D. J. Changes in anterior chamber flare and cells following cataract surgery. Br. J. Ophthalmol. 78, 91\u201394 (1994).","journal-title":"Br. J. Ophthalmol."},{"key":"85495_CR2","first-page":"1410","volume":"39","author":"N Wallentin","year":"1998","unstructured":"Wallentin, N., Wickstr\u00f6m, K. & Lundberg, C. Effect of cataract surgery on aqueous TGF-\u03b2 and lens epithelial cell proliferation. Investig. Ophthalmol. Vis. Sci. 39, 1410\u20131418 (1998).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"85495_CR3","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1097\/ICU.0b013e32834cd60e","volume":"23","author":"P Taravati","year":"2012","unstructured":"Taravati, P., Lam, D. L., Leveque, T. & Van Gelder, R. N. Postcataract surgical inflammation. Curr. Opin. Ophthalmol. 23, 12\u201318 (2012).","journal-title":"Curr. Opin. Ophthalmol."},{"key":"85495_CR4","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1016\/S0886-3350(03)00411-5","volume":"29","author":"O Findl","year":"2003","unstructured":"Findl, O., Amon, M., Petternel, V. & Kruger, A. Early objective assessment of intraocular inflammation after phacoemulsification cataract surgery. J. Cataract Refract. Surg. 29, 2143\u20132147 (2003).","journal-title":"J. Cataract Refract. Surg."},{"key":"85495_CR5","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/S0886-3350(97)80256-8","volume":"23","author":"JL Alio","year":"1997","unstructured":"Alio, J. L., Sayans, J. A. & Chipont, E. Flare-cell meter measurement of inflammation after uneventful cataract surgery with intraocular lens implantation. J. Cataract Refract. Surg. 23, 935\u2013939 (1997).","journal-title":"J. Cataract Refract. Surg."},{"key":"85495_CR6","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/eye.2000.13","volume":"14","author":"J Schauersberger","year":"2000","unstructured":"Schauersberger, J. et al. Long-term disorders of the blood-aqueous barrier after small-incision cataract surgery. Eye (Lond) 14, 61\u201363 (2000).","journal-title":"Eye (Lond)"},{"key":"85495_CR7","doi-asserted-by":"publisher","first-page":"7951","DOI":"10.1167\/iovs.12-10231","volume":"53","author":"M Kawai","year":"2012","unstructured":"Kawai, M. et al. Elevated levels of monocyte chemoattractant protein-1 in the aqueous humor after phacoemulsification. Investig. Ophthalmol. Vis. Sci. 53, 7951\u20137960 (2012).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"85495_CR8","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/j.jcrs.2012.04.028","volume":"38","author":"T Inoue","year":"2012","unstructured":"Inoue, T. et al. Simultaneous increases in multiple proinflammatory cytokines in the aqueous humor in pseudophakic glaucomatous eyes. J. Cataract Refract. Surg. 38, 1389\u20131397 (2012).","journal-title":"J. Cataract Refract. Surg."},{"key":"85495_CR9","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1001\/archophthalmol.2010.348","volume":"129","author":"Y Takihara","year":"2011","unstructured":"Takihara, Y. et al. Trabeculectomy with mitomycin for open-angle glaucoma in phakic versus pseudophakic eyes after phacoemulsification. Arch. Ophthalmol. 129, 152\u2013157 (2011).","journal-title":"Arch. Ophthalmol."},{"key":"85495_CR10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1001\/jamaophthalmol.2013.5605","volume":"132","author":"Y Takihara","year":"2014","unstructured":"Takihara, Y. et al. Trabeculectomy for open-angle glaucoma in phakic eyes vs in pseudophakic eyes after phacoemulsification: A prospective clinical cohort study. JAMA Ophthalmol. 132, 69\u201376 (2014).","journal-title":"JAMA Ophthalmol."},{"key":"85495_CR11","doi-asserted-by":"publisher","first-page":"e96481","DOI":"10.1371\/journal.pone.0096481","volume":"9","author":"T Kida","year":"2014","unstructured":"Kida, T. et al. Pharmacokinetics and efficacy of topically applied nonsteroidal anti-inflammatory drugs in retinochoroidal tissues in rabbits. PLoS ONE 9, e96481 (2014).","journal-title":"PLoS ONE"},{"key":"85495_CR12","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1089\/jop.2007.0132","volume":"24","author":"K Miyake","year":"2008","unstructured":"Miyake, K., Ogawa, T., Tajika, T., Gow, J. A. & McNamara, T. R. Ocular pharmacokinetics of a single dose of bromfenac sodium ophthalmic solution 0.1% in human aqueous humor. J. Ocul. Pharmacol. Ther. 24, 573\u2013578 (2008).","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"85495_CR13","doi-asserted-by":"publisher","first-page":"3559","DOI":"10.1167\/iovs.15-16489","volume":"56","author":"T Matsumura","year":"2015","unstructured":"Matsumura, T. et al. Changes in matrix metalloproteinases in diabetes patients\u2019 tears after vitrectomy and the relationship with corneal epithelial disorder. Investig. Ophthalmol. Vis. Sci. 56, 3559\u20133564 (2015).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"85495_CR14","first-page":"221","volume":"21","author":"MA Lemp","year":"1995","unstructured":"Lemp, M. A. Report of the National Eye Institute\/Industry workshop on clinical trials in dry eyes. CLAO J. 21, 221\u2013232 (1995).","journal-title":"CLAO J."},{"key":"85495_CR15","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1001\/archopht.1989.01070010071030","volume":"107","author":"JP Joseph","year":"1989","unstructured":"Joseph, J. P., Grierson, I. & Hitchings, R. A. Chemotactic activity of aqueous humor: A cause of failure of trabeculectomies?. Arch. Ophthalmol. 107, 69\u201374 (1989).","journal-title":"Arch. Ophthalmol."},{"key":"85495_CR16","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/84205","volume":"2","author":"SA Luther","year":"2001","unstructured":"Luther, S. A. & Cyster, J. G. Chemokines as regulators of T cell differentiation. Nat. Immunol. 2, 102\u2013107 (2001).","journal-title":"Nat. Immunol."},{"key":"85495_CR17","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1172\/JCI1020","volume":"101","author":"LA DiPietro","year":"1998","unstructured":"DiPietro, L. A., Burdick, M., Low, Q. E., Kunkel, S. L. & Strieter, R. M. MIP-1alpha as a critical macrophage chemoattractant in murine wound repair. J. Clin. Investig. 101, 1693\u20131698 (1998).","journal-title":"J. Clin. Investig."},{"key":"85495_CR18","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1161\/01.ATV.19.9.2085","volume":"19","author":"KSC Weber","year":"1999","unstructured":"Weber, K. S. C., Nelson, P. J., Gro, H. & Weber, C. Expression of CCR2 by endothelial cells: Implications for MCP-1 mediated wound injury repair and In vivo inflammatory activation of endothelium. Arterioscler. Thromb. Vasc. Biol. 19, 2085\u20132093 (1999).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"85495_CR19","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/S0886-3350(98)80296-4","volume":"24","author":"A Kruger","year":"1998","unstructured":"Kruger, A. et al. Postoperative inflammation after clear corneal and sclerocorneal incisions. J. Cataract Refract. Surg. 24, 524\u2013528 (1998).","journal-title":"J. Cataract Refract. Surg."},{"key":"85495_CR20","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1517\/14656560903188425","volume":"10","author":"J Jones","year":"2009","unstructured":"Jones, J. & Francis, P. Ophthalmic utility of topical bromfenac, a twice-daily nonsteroidal anti-inflammatory agent. Expert Opin. Pharmacother. 10, 2379\u20132385 (2009).","journal-title":"Expert Opin. Pharmacother."},{"key":"85495_CR21","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1001\/jamaophthalmol.2013.6203","volume":"132","author":"SD Schoenberger","year":"2014","unstructured":"Schoenberger, S. D., Kim, S. J., Shah, R., Sheng, J. & Cherney, E. Reduction of interleukin 8 and platelet-derived growth factor levels by topical ketorolac, 0.45%, in patients with diabetic retinopathy. JAMA Ophthalmol. 132, 32\u201337 (2014).","journal-title":"JAMA Ophthalmol."},{"key":"85495_CR22","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1056\/NEJM199412013312203","volume":"331","author":"LP Aiello","year":"1994","unstructured":"Aiello, L. P. et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N. Engl. J. Med. 331, 1480\u20131487 (1994).","journal-title":"N. Engl. J. Med."},{"key":"85495_CR23","doi-asserted-by":"publisher","first-page":"16012","DOI":"10.1038\/nrdp.2016.12","volume":"2","author":"TY Wong","year":"2016","unstructured":"Wong, T. Y., Cheung, C. M. G., Larsen, M., Sharma, S. & Sim\u00f3, R. Diabetic retinopathy. Nat. Rev. Dis. Primers 2, 16012 (2016).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"85495_CR24","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.1167\/iovs.13-13587","volume":"55","author":"SH Jung","year":"2014","unstructured":"Jung, S. H., Kim, K. A., Sohn, S. W. & Yang, S. J. Association of aqueous humor cytokines with the development of retinal ischemia and recurrent macular edema in retinal vein occlusion. Investig. Ophthalmol. Vis. Sci. 55, 2290\u20132296 (2014).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"85495_CR25","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.preteyeres.2015.06.002","volume":"49","author":"PA Campochiaro","year":"2015","unstructured":"Campochiaro, P. A. Molecular pathogenesis of retinal and choroidal vascular diseases. Prog. Retin. Eye Res. 49, 67\u201381 (2015).","journal-title":"Prog. Retin. Eye Res."},{"key":"85495_CR26","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1007\/s00417-017-3595-z","volume":"255","author":"J Siedlecki","year":"2017","unstructured":"Siedlecki, J. et al. Combined VEGF and PDGF inhibition for neovascular AMD: Anti-angiogenic properties of axitinib on human endothelial cells and pericytes in vitro. Graefes Arch. Clin. Exp. Ophthalmol. 255, 963\u2013972 (2017).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"85495_CR27","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/s00417-017-3599-8","volume":"255","author":"P Duan","year":"2017","unstructured":"Duan, P., Liu, Y. & Li, J. The comparative efficacy and safety of topical non-steroidal anti-inflammatory drugs for the treatment of anterior chamber inflammation after cataract surgery: A systematic review and network meta-analysis. Graefes Arch. Clin. Exp. Ophthalmol. 255, 639\u2013649 (2017).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"85495_CR28","doi-asserted-by":"publisher","first-page":"233","DOI":"10.2165\/00002018-200225040-00002","volume":"25","author":"BI Gaynes","year":"2002","unstructured":"Gaynes, B. I. & Fiscella, R. Topical nonsteroidal anti-inflammatory drugs for ophthalmic use: A safety review. Drug Saf. 25, 233\u2013250 (2002).","journal-title":"Drug Saf."},{"key":"85495_CR29","doi-asserted-by":"publisher","first-page":"2712","DOI":"10.1007\/s12325-019-01076-4","volume":"36","author":"M Coassin","year":"2019","unstructured":"Coassin, M. et al. Anterior chamber inflammation after cataract surgery: A randomized clinical trial comparing bromfenac 0.09% to dexamethasone 0.1%. Adv. Ther. 36, 2712\u20132722 (2019).","journal-title":"Adv. Ther."},{"key":"85495_CR30","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1159\/000346847","volume":"229","author":"QW Wang","year":"2013","unstructured":"Wang, Q. W. et al. Bromfenac sodium 0.1%, fluorometholone 0.1% and dexamethasone 0.1% for control of ocular inflammation and prevention of cystoid macular edema after phacoemulsification. Ophthalmologica 229, 187\u2013194 (2013).","journal-title":"Ophthalmologica"},{"key":"85495_CR31","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1080\/02713683.2017.1396615","volume":"43","author":"C Campa","year":"2018","unstructured":"Campa, C., Salsini, G. & Perri, P. Comparison of the efficacy of dexamethasone, nepafenac, and bromfenac for preventing pseudophakic cystoid macular edema: An open-label, prospective, randomized controlled trial. Curr. Eye Res. 43, 362\u2013367 (2018).","journal-title":"Curr. Eye Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85495-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85495-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85495-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T05:13:00Z","timestamp":1670044380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85495-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,16]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["85495"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-85495-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,16]]},"assertion":[{"value":"2 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.I. is responsible for submitting a competing financial interest statement on behalf of all authors of the paper. M.I.\u2019s work has been partially funded by HOYA, Novartis, Pfizer, Alcon, Senju, Santen, Kowa, Otsuka, NIDEK, Wakamoto, and AMO. R.T.\u2019s work has been partially funded by Senju. The other authors declare no potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6018"}}