{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T21:44:46Z","timestamp":1782251086043,"version":"3.54.5"},"reference-count":23,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010795","name":"Chugai Pharmaceutical","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100010795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Anti\u2013vascular endothelial growth factor (anti-VEGF) agents are generally considered to be the first line of therapy for macular edema due to retinal vein occlusion (RVO-ME). However, current anti-VEGF treatment regimens in Japan are unable to maintain long-term vision improvement, particularly in patients with central RVO-ME (CRVO-ME). Faricimab is a dual angiopoietin-2\/VEGF inhibitor approved for the treatment of RVO-ME in Japan. The RVOSTAR study is being conducted to evaluate the long-term maintenance of vision outcomes with faricimab using a modified treat-and-extend (T&amp;E) regimen in treatment-na\u00efve Japanese patients with CRVO-ME or hemi\u2013RVO-ME (HRVO-ME) and to assess the factors affecting visual acuity and treatment intervals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and design<\/jats:title>\n                    <jats:p>RVOSTAR (Japan Registry of Clinical Trials; jRCTs041250001) is an unmasked, single-arm, multicenter, prospective interventional study. Patients with CRVO-ME or HRVO-ME will 1) receive faricimab 6\u2009mg every 4 weeks (\u22646 injections) until ME is resolved; 2) be observed with no treatment until ME reoccurs, based on pre-specified central subfield thickness (CST) criteria; and then 3) be treated according to a T&amp;E regimen up to 72 weeks, with dosing intervals based on time to relapse and adjusted by 4-week increments (minimum interval: every 4 weeks; maximum interval: no limit). Vision outcomes include best-corrected visual acuity (BCVA) and CST. The primary endpoint is the change from baseline in BCVA at week 72. Safety outcomes include ocular and non-ocular adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>RVOSTAR will evaluate the long-term maintenance of vision outcomes with a modified faricimab T&amp;E regimen in patients with CRVO-ME or HRVO-ME while reducing the burden associated with frequent injections. The findings from this study may help to optimize dosing frequency in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0335015","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:42:09Z","timestamp":1761846129000},"page":"e0335015","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["A multicenter, single-arm study using a modified faricimab treat-and-extend regimen in patients with macular edema due to central retinal vein occlusion: RVOSTAR study design protocol"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4569-1792","authenticated-orcid":true,"given":"Mineo","family":"Kondo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Shimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0779-7799","authenticated-orcid":true,"given":"Akitaka","family":"Tsujikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Muraoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Akiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Hama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tsujimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Kamei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"issue":"1","key":"pone.0335015.ref001","first-page":"40","article-title":"Retinal vein occlusion review","volume":"7","author":"M Ip","year":"2018","journal-title":"Asia Pac J Ophthalmol (Phila)"},{"issue":"8","key":"pone.0335015.ref002","doi-asserted-by":"crossref","first-page":"5905","DOI":"10.1167\/iovs.11-7775","article-title":"Nine-year incidence and risk factors for retinal vein occlusion in a general Japanese population: the Hisayama Study","volume":"52","author":"S Arakawa","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"pone.0335015.ref003","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.ophtha.2011.12.005","article-title":"Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial","volume":"119","author":"JS Heier","year":"2012","journal-title":"Ophthalmology"},{"issue":"5","key":"pone.0335015.ref004","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.ajo.2014.07.027","article-title":"Intravitreal aflibercept for macular edema secondary to central retinal vein occlusion: 18-month results of the phase 3 GALILEO study","volume":"158","author":"Y Ogura","year":"2014","journal-title":"Am J Ophthalmol"},{"issue":"7","key":"pone.0335015.ref005","doi-asserted-by":"crossref","DOI":"10.1016\/j.ophtha.2014.01.027","article-title":"Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study","volume":"121","author":"JS Heier","year":"2014","journal-title":"Ophthalmology"},{"issue":"10","key":"pone.0335015.ref006","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1016\/j.ophtha.2011.02.038","article-title":"Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study","volume":"118","author":"PA Campochiaro","year":"2011","journal-title":"Ophthalmology"},{"issue":"1","key":"pone.0335015.ref007","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41433-022-02020-7","article-title":"Efficacy, safety, and treatment burden of treat-and-extend versus alternative anti-VEGF regimens for nAMD: a systematic review and meta-analysis","volume":"37","author":"D Rosenberg","year":"2023","journal-title":"Eye (Lond)"},{"key":"pone.0335015.ref008","unstructured":"Pharmaceuticals and Medical Devices Agency. 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