{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:32:08Z","timestamp":1784381528696,"version":"3.55.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T00:00:00Z","timestamp":1709337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T00:00:00Z","timestamp":1709337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100015993","name":"Kowa Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Graefes Arch Clin Exp Ophthalmol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>To evaluate the long-term efficacy and safety of ripasudil-brimonidine fixed-dose combination (RBFC), a new intraocular pressure (IOP)-lowering medication for glaucoma and ocular hypertension (OHT).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This prospective, multicentre (23 sites in Japan), open-label study enrolled patients with primary open-angle glaucoma (POAG), OHT or exfoliative glaucoma and assigned them to one of four combination therapy cohorts, based on previous treatment(s) received: prostaglandin (PG) analogue (Cohort 1); PG analogue and beta-adrenoceptor blocker (\u03b2-blocker) (Cohort 2); PG analogue, \u03b2-blocker and carbonic anhydrase inhibitor (Cohort 3); or other\/no treatment (Cohort 4). After a \u2265 4-week screening period, eligible patients received twice-daily RBFC for 52\u00a0weeks in addition to the treatments they were already receiving. Efficacy was assessed by change in IOP from baseline through week 52. Adverse events and adverse drug reactions (ADRs) were monitored throughout.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In total, 179 patients from Cohort 1 (<jats:italic>n<\/jats:italic> = 48), Cohort 2 (<jats:italic>n<\/jats:italic> = 44), Cohort 3 (<jats:italic>n<\/jats:italic> = 41) and Cohort 4 (<jats:italic>n<\/jats:italic> = 46) entered the RBFC treatment period. For all cohorts, mean IOP was significantly reduced at 11:00 (2\u00a0h after instillation of RBFC) through week 52 with the changes from baseline at week 52 of \u2212 2.7 to \u2212 4.1\u00a0mmHg across cohorts; all <jats:italic>p<\/jats:italic> &lt; 0.001. Common ADRs were conjunctival hyperaemia (58%), allergic conjunctivitis (18%) and blepharitis (17%), most of which were mild in severity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>These data demonstrated the long-term efficacy and safety of RBFC, both alone and in combination with other anti-glaucoma agents. RBFC may offer a new treatment option for the long-term management of glaucoma and OHT.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>Japan Registry of Clinical Trials Identifier: jRCT2080225063.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Date of registration<\/jats:title>\n                <jats:p>17 February 2020.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00417-024-06388-y","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T09:02:08Z","timestamp":1709370128000},"page":"2579-2591","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Long-term intraocular pressure-lowering efficacy and safety of ripasudil-brimonidine fixed-dose combination for glaucoma and ocular hypertension: a multicentre, open-label, phase 3 study"],"prefix":"10.1007","volume":"262","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0356-7411","authenticated-orcid":false,"given":"Hidenobu","family":"Tanihara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6683-0144","authenticated-orcid":false,"given":"Tetsuya","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6810-0583","authenticated-orcid":false,"given":"Makoto","family":"Aihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6940-1334","authenticated-orcid":false,"given":"Noriko","family":"Koizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6350-2599","authenticated-orcid":false,"given":"Atsuki","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kawakita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toka","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9130-0137","authenticated-orcid":false,"given":"Hideki","family":"Suganami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"K-232 Clinical Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitsugu","family":"Tagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakae","family":"Matsuzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Okayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Setsuko","family":"Hashida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachi Amaki","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Kiyosawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Asai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzuru","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoji","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehito","family":"Kawabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Muramatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikki","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Migita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,2]]},"reference":[{"key":"6388_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/bjophthalmol-2021-egsguidelines","volume":"105","author":"European Glaucoma Society","year":"2021","unstructured":"European Glaucoma Society (2021) European Glaucoma Society terminology and guidelines for glaucoma, 5th edition. Br J Ophthalmol 105:1\u2013169. https:\/\/doi.org\/10.1136\/bjophthalmol-2021-egsguidelines","journal-title":"Br J Ophthalmol"},{"key":"6388_CR2","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.ophtha.2020.10.022","volume":"128","author":"SJ Gedde","year":"2021","unstructured":"Gedde SJ, Vinod K, Wright MM, Muir KW, Lind JT, Chen PP, Li T, Mansberger SL (2021) Primary open-angle glaucoma preferred practice pattern\u00ae.\u00a0Ophthalmology\u00a0128:71\u2013150. https:\/\/doi.org\/10.1016\/j.ophtha.2020.10.022","journal-title":"Ophthalmol"},{"key":"6388_CR3","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s10384-022-00970-9","volume":"67","author":"Y Kiuchi","year":"2023","unstructured":"Kiuchi Y, Inoue T, Shoji N, Nakamura M, Tanito M, Glaucoma Guideline Preparation Committee, Japan Glaucoma Society (2023) The Japan Glaucoma Society guidelines for glaucoma 5th edition. Jpn J Ophthalmol 67:189\u2013254. https:\/\/doi.org\/10.1007\/s10384-022-00970-9","journal-title":"Jpn J Ophthalmol"},{"key":"6388_CR4","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/S0161-6420(02)01974-7","volume":"110","author":"PP Chen","year":"2003","unstructured":"Chen PP (2003) Blindness in patients with treated open-angle glaucoma.\u00a0Ophthalmology\u00a0110:726\u2013733. https:\/\/doi.org\/10.1016\/S0161-6420(02)01974-7","journal-title":"Ophthalmol"},{"key":"6388_CR5","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.ophtha.2019.10.022","volume":"127","author":"PA Newman-Casey","year":"2020","unstructured":"Newman-Casey PA, Niziol LM, Gillespie BW, Janz NK, Lichter PR, Musch DC (2020) The association between medication adherence and visual field progression in the collaborative initial glaucoma treatment study. Ophthalmology 127:477\u2013483. https:\/\/doi.org\/10.1016\/j.ophtha.2019.10.022","journal-title":"Ophthalmology"},{"key":"6388_CR6","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.ophtha.2004.12.026","volume":"112","author":"AL Robin","year":"2005","unstructured":"Robin AL, Covert D (2005) Does adjunctive glaucoma therapy affect adherence to the initial primary therapy? Ophthalmology 112:863\u2013868. https:\/\/doi.org\/10.1016\/j.ophtha.2004.12.026","journal-title":"Ophthalmology"},{"key":"6388_CR7","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.ajo.2007.06.012","volume":"144","author":"AL Robin","year":"2007","unstructured":"Robin AL, Novack GD, Covert DW, Crockett RS, Marcic TS (2007) Adherence in glaucoma: objective measurements of once-daily and adjunctive medication use. Am J Ophthalmol 144:533\u2013540. https:\/\/doi.org\/10.1016\/j.ajo.2007.06.012","journal-title":"Am J Ophthalmol"},{"key":"6388_CR8","doi-asserted-by":"publisher","first-page":"S30","DOI":"10.1016\/j.ophtha.2009.06.024","volume":"116","author":"JC Tsai","year":"2009","unstructured":"Tsai JC (2009) A comprehensive perspective on patient adherence to topical glaucoma therapy.\u00a0Ophthalmology\u00a0116:S30\u2013S36. https:\/\/doi.org\/10.1016\/j.ophtha.2009.06.024","journal-title":"Ophthalmol"},{"key":"6388_CR9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.ajo.2016.12.002","volume":"176","author":"HS Barnebey","year":"2017","unstructured":"Barnebey HS, Robin AL (2017) Adherence to fixed-combination versus unfixed travoprost 0.004%\/timolol 0.5% for glaucoma or ocular hypertension: a randomized trial. Am J Ophthalmol 176:61\u201369. https:\/\/doi.org\/10.1016\/j.ajo.2016.12.002","journal-title":"Am J Ophthalmol"},{"key":"6388_CR10","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s12886-021-01813-w","volume":"21","author":"C Shirai","year":"2021","unstructured":"Shirai C, Matsuoka N, Nakazawa T (2021) Comparison of adherence between fixed and unfixed topical combination glaucoma therapies using Japanese healthcare\/pharmacy claims database: a retrospective non-interventional cohort study. BMC Ophthalmol 21:52. https:\/\/doi.org\/10.1186\/s12886-021-01813-w","journal-title":"BMC Ophthalmol"},{"key":"6388_CR11","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ajo.2022.11.017","volume":"248","author":"H Tanihara","year":"2023","unstructured":"Tanihara H, Yamamoto T, Aihara M, Kawakita K, Kojima S, Kanazawa M, Nojima T, Suganami H, K-232 Clinical Study Group (2023) Ripasudil-brimonidine fixed-dose combination vs ripasudil or brimonidine: two phase 3 randomized clinical trials. Am J Ophthalmol 248:35\u201344. https:\/\/doi.org\/10.1016\/j.ajo.2022.11.017","journal-title":"Am J Ophthalmol"},{"key":"6388_CR12","first-page":"679","volume":"29","author":"M Araie","year":"2012","unstructured":"Araie M, Yamazaki Y, Sugiyama K, Kuwayama Y, Tanihara H (2012) Long-term safety and efficacy of brimonidine ophthalmic solution in patients with primary open angle glaucoma or ocular hypertension [in Japanese]. Atarashii Ganka (J Eye) 29:679\u2013686","journal-title":"Atarashii Ganka (J Eye)"},{"key":"6388_CR13","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/s0002-9394(98)00286-4","volume":"127","author":"LJ Katz","year":"1999","unstructured":"Katz LJ (1999) Brimonidine tartrate 0.2% twice daily vs timolol 0.5% twice daily: 1-year results in glaucoma patients. Am J Ophthalmol 127:20\u201326. https:\/\/doi.org\/10.1016\/s0002-9394(98)00286-4","journal-title":"Am J Ophthalmol"},{"key":"6388_CR14","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1016\/s0161-6420(98)91048-x","volume":"105","author":"RP LeBlanc","year":"1998","unstructured":"LeBlanc RP (1998) Twelve-month results of an ongoing randomized trial comparing brimonidine tartrate 0.2% and timolol 0.5% given twice daily in patients with glaucoma or ocular hypertension. Ophthalmology 105:1960\u20131967. https:\/\/doi.org\/10.1016\/s0161-6420(98)91048-x","journal-title":"Ophthalmology"},{"key":"6388_CR15","doi-asserted-by":"publisher","first-page":"e26","DOI":"10.1111\/aos.12829","volume":"94","author":"H Tanihara","year":"2016","unstructured":"Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Fukushima A, Suganami H, Araie M (2016) One-year clinical evaluation of 0.4% ripasudil (K-115) in patients with open-angle glaucoma and ocular hypertension. Acta Ophthalmol 94:e26\u2013e34. https:\/\/doi.org\/10.1111\/aos.12829","journal-title":"Acta Ophthalmol"},{"key":"6388_CR16","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1007\/s12325-021-02023-y","volume":"39","author":"H Tanihara","year":"2022","unstructured":"Tanihara H, Kakuda T, Sano T, Kanno T, Kurihara Y (2022) Long-term intraocular pressure-lowering effects and adverse events of ripasudil in patients with glaucoma or ocular hypertension over 24 months. Adv Ther 39:1659\u20131677. https:\/\/doi.org\/10.1007\/s12325-021-02023-y","journal-title":"Adv Ther"},{"key":"6388_CR17","doi-asserted-by":"publisher","first-page":"3559","DOI":"10.1007\/s12325-023-02534-w","volume":"40","author":"H Tanihara","year":"2023","unstructured":"Tanihara H, Yamamoto T, Aihara M, Koizumi N, Minami H, Kojima S, Isobe T, Kanazawa M, Suganami H (2023) Crossover randomized study of pharmacologic effects of ripasudil-brimonidine fixed-dose combination versus ripasudil or brimonidine. Adv Ther 40:3559\u20133573. https:\/\/doi.org\/10.1007\/s12325-023-02534-w","journal-title":"Adv Ther"},{"key":"6388_CR18","doi-asserted-by":"publisher","first-page":"10308","DOI":"10.1038\/s41598-020-66928-4","volume":"10","author":"A Futakuchi","year":"2020","unstructured":"Futakuchi A, Morimoto T, Ikeda Y, Tanihara H, Inoue T, ROCK-S Study Group Collaborators (2020) Intraocular pressure-lowering effects of ripasudil in uveitic glaucoma, exfoliation glaucoma, and steroid-induced glaucoma patients: ROCK-S, a multicentre historical cohort study. Sci Rep 10:10308. https:\/\/doi.org\/10.1038\/s41598-020-66928-4","journal-title":"Sci Rep"},{"key":"6388_CR19","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1097\/IJG.0000000000001203","volume":"28","author":"H Saito","year":"2019","unstructured":"Saito H, Kagami S, Mishima K, Mataki N, Fukushima A, Araie M (2019) Long-term side effects including blepharitis leading to discontinuation of ripasudil. J Glaucoma 28:289\u2013293. https:\/\/doi.org\/10.1097\/IJG.0000000000001203","journal-title":"J Glaucoma"},{"key":"6388_CR20","doi-asserted-by":"publisher","first-page":"e0136802","DOI":"10.1371\/journal.pone.0136802","volume":"10","author":"H Nakagawa","year":"2015","unstructured":"Nakagawa H, Koizumi N, Okumura N, Suganami H, Kinoshita S (2015) Morphological changes of human corneal endothelial cells after rho-associated kinase inhibitor eye drop (ripasudil) administration: a prospective open-label clinical study. PLoS ONE 10:e0136802. https:\/\/doi.org\/10.1371\/journal.pone.0136802","journal-title":"PLoS ONE"},{"key":"6388_CR21","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1136\/bjophthalmol-2019-315776","volume":"105","author":"Y Maruyama","year":"2021","unstructured":"Maruyama Y, Ikeda Y, Mori K, Yoshii K, Ueno M, Yoshikawa H, Sotozono C, Kinoshita S (2021) Morphological change and recovery of corneal endothelial cells after rho-associated protein kinase inhibitor eye-drop (ripasudil 0.4%) instillation. Br J Ophthalmol 105:169\u2013173. https:\/\/doi.org\/10.1136\/bjophthalmol-2019-315776","journal-title":"Br J Ophthalmol"},{"key":"6388_CR22","doi-asserted-by":"publisher","first-page":"39","DOI":"10.2131\/fts.1.39","volume":"1","author":"E Wato","year":"2014","unstructured":"Wato E, Omichi K, Yoneyama S, Tanaka M, Kagawa M, Amano Y (2014) Safety evaluation of morphological changes in corneal endothelial cells induced by K-115 in cynomolgus monkeys. Fund Toxicol Sci 1:39\u201347. https:\/\/doi.org\/10.2131\/fts.1.39","journal-title":"Fund Toxicol Sci"},{"key":"6388_CR23","doi-asserted-by":"publisher","first-page":"7560","DOI":"10.1167\/iovs.15-17887","volume":"56","author":"N Okumura","year":"2015","unstructured":"Okumura N, Okazaki Y, Inoue R, Nakano S, Fullwood NJ, Kinoshita S, Koizumi N (2015) Rho-associated kinase inhibitor eye drop (ripasudil) transiently alters the morphology of corneal endothelial cells. Investig Ophthalmol Vis Sci\u00a056:7560\u20137567. https:\/\/doi.org\/10.1167\/iovs.15-17887","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"6388_CR24","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1097\/IJG.0b013e3182952213","volume":"24","author":"RF Wang","year":"2015","unstructured":"Wang RF, Williamson JE, Kopczynski C, Serle JB (2015) Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma 24:51\u201354. https:\/\/doi.org\/10.1097\/IJG.0b013e3182952213","journal-title":"J Glaucoma"},{"key":"6388_CR25","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1016\/j.bmcl.2016.03.104","volume":"26","author":"JM Sturdivant","year":"2016","unstructured":"Sturdivant JM, Royalty SM, Lin CW, Moore LA, Yingling JD, Laethem CL, Sherman B, Heintzelman GR, Kopczynski CC, deLong MA (2016) Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma. Bioorg Med Chem Lett 26:2475\u20132480. https:\/\/doi.org\/10.1016\/j.bmcl.2016.03.104","journal-title":"Bioorg Med Chem Lett"},{"key":"6388_CR26","doi-asserted-by":"publisher","first-page":"4639","DOI":"10.1007\/s12325-023-02550-w","volume":"40","author":"M Araie","year":"2023","unstructured":"Araie M, Sugiyama K, Aso K, Kanemoto K, Iwata R, Hollander DA, Senchyna M, Kopczynski CC (2023) Phase 3 clinical trial comparing the safety and efficacy of netarsudil to ripasudil in patients with primary open-angle glaucoma or ocular hypertension: Japan Rho kinase elevated intraocular pressure treatment trial (J-ROCKET). Adv Ther 40:4639\u20134656. https:\/\/doi.org\/10.1007\/s12325-023-02550-w","journal-title":"Adv Ther"},{"key":"6388_CR27","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.ajo.2019.01.003","volume":"200","author":"MY Kahook","year":"2019","unstructured":"Kahook MY, Serle JB, Mah FS, Kim T, Raizman MB, Heah T, Ramirez-Davis N, Kopczynski CC, Usner DW, Novack GD (2019) Long-term safety and ocular hypotensive efficacy evaluation of netarsudil ophthalmic solution: Rho kinase elevated IOP treatment trial (ROCKET-2). Am J Ophthalmol 200:130\u2013137. https:\/\/doi.org\/10.1016\/j.ajo.2019.01.003","journal-title":"Am J Ophthalmol"},{"key":"6388_CR28","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3109\/09273948.2015.1037845","volume":"24","author":"J Beltz","year":"2016","unstructured":"Beltz J, Zamir E (2016) Brimonidine induced anterior uveitis. Ocul Immunol Inflamm 24:128\u2013133. https:\/\/doi.org\/10.3109\/09273948.2015.1037845","journal-title":"Ocul Immunol Inflamm"},{"key":"6388_CR29","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/s0002-9394(00)00491-8","volume":"130","author":"DB Byles","year":"2000","unstructured":"Byles DB, Frith P, Salmon JF (2000) Anterior uveitis as a side effect of topical brimonidine. Am J Ophthalmol 130:287\u2013291. https:\/\/doi.org\/10.1016\/s0002-9394(00)00491-8","journal-title":"Am J Ophthalmol"},{"key":"6388_CR30","doi-asserted-by":"publisher","first-page":"5584","DOI":"10.1167\/iovs.17-22679","volume":"58","author":"T Uchida","year":"2017","unstructured":"Uchida T, Honjo M, Yamagishi R, Aihara M (2017) The anti-inflammatory effect of ripasudil (K-115), a Rho kinase (ROCK) inhibitor, on endotoxin-induced uveitis in rats. Investig Ophthalmol Vis Sci 58:5584\u20135593. https:\/\/doi.org\/10.1167\/iovs.17-22679","journal-title":"Investig Ophthalmol Vis Sci"}],"container-title":["Graefe's Archive for Clinical and Experimental Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00417-024-06388-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00417-024-06388-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00417-024-06388-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T09:03:48Z","timestamp":1721379828000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00417-024-06388-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,2]]},"references-count":30,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["6388"],"URL":"https:\/\/doi.org\/10.1007\/s00417-024-06388-y","relation":{},"ISSN":["0721-832X","1435-702X"],"issn-type":[{"value":"0721-832X","type":"print"},{"value":"1435-702X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,2]]},"assertion":[{"value":"23 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in compliance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The protocol was approved by the Medical Corporation Heishinkai OPHAC Hospital IRB, Medical Corporation Cattleyakai Dr. Mano Medical Clinic IRB, Medical Corporation Shintokai Yokohama Minoru Clinic Institutional Review Board, Review Board of Human Rights and Ethics for Clinical Studies Institutional Review Board, and the ShinAkasaka Clinic Institutional Review Board (now known as the ShinAkasaka Clinic Aoyama Institutional Review Board). This study is registered with the Japan Registry of Clinical Trials (jRCT identifier: jRCT2080225063).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent for study participation was obtained from all subjects prior to study entry.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Subjects signed informed consent regarding the publication of their data.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"All named authors attest that they meet the four criteria of authorship, as defined by the International Committee of Medical Journal Editors (ICMJE). All authors have participated sufficiently in the work and accept public responsibility for the appropriate portions of the content, as well as accepting responsibility for the integrity of their co-authors.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authorship"}},{"value":"This manuscript is based on work that was previously presented as an abstract at the 127th Annual Meeting of the Japanese Ophthalmological Society (6\u20139 April 2023; Tokyo, Japan).","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Prior presentation"}},{"value":"Hidenobu Tanihara has received consulting fees, lecture fees, financial support and drugs from Kowa Company, Ltd. Tetsuya Yamamoto has received consulting fees from Alcon Japan, Allergan Japan, Kowa Company, Ltd. and Santen Pharmaceutical; board membership fees from Kowa Company, Ltd., Otsuka Pharmaceutical, Rohto Pharmaceutical and Santen Pharmaceutical; financial support from Pfizer Japan, Otsuka Pharmaceutical, Santen Pharmaceutical and Senju Pharmaceutical; and lecture fees from Johnson & Johnson, Kowa Company, Ltd., Pfizer Japan, Nitto Medic, Novartis, Otsuka Pharmaceutical, Santen Pharmaceutical, Senju Pharmaceutical and Viatris. Makoto Aihara has received consulting fees from Santen Pharmaceutical, Senju Pharmaceutical, Alcon Japan, Pfizer Japan, Kowa Company, Ltd., Otsuka Pharmaceutical, Wakamoto Pharmaceutical, HOYA, Glaukos, IRIDEX, CREWT Medical Systems, Inc. and Astellas Pharmaceutical; financial support from Santen Pharmaceutical, Senju Pharmaceutical, Alcon Japan, Novartis, Pfizer Japan, Kowa Company, Ltd., Otsuka Pharmaceutical, Wakamoto Pharmaceutical, Johnson & Johnson, Glaukos, TOMEY, Ono Pharmaceutical, CREWT Medical Systems, Inc. and Sato Pharmaceutical; and lecture and travel fees and drugs from Santen Pharmaceutical, Senju Pharmaceutical, Alcon Japan, Novartis, Pfizer Japan, Kowa Company, Ltd., Otsuka Pharmaceutical, Johnson & Johnson, HOYA, Glaukos, TOMEY, IRIDEX, CREWT Medical Systems, Inc., CANON, Carl Zeiss Meditec and Sato Pharmaceutical. Noriko Koizumi has received consulting fees from Kowa Company, Ltd. and M's Science Corporation; lecture fees from Kowa Company, Ltd., Senju Pharmaceutical and Santen Pharmaceutical; and financial support from ActualEyes Inc. Atsuki Fukushima received consulting fees from Johnson & Johnson, Kowa Company, Ltd. and Santen Pharmaceutical; and lecture fees from Santen Pharmaceutical, Senju Pharmaceutical, Novartis, Johnson & Johnson, Tanabe-Mitsubishi and Rohto-nitten. Koji Kawakita, Satoshi Kojima, Toka Nakamura and Hideki Suganami are employees of Kowa Company, Ltd.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}