{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:01:13Z","timestamp":1785124873251,"version":"3.55.0"},"reference-count":40,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"unspecified","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81371043"],"award-info":[{"award-number":["81371043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017661","name":"China Health Promotion Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Research Program of Chongqing Municipal Education Commission","award":["KJZD-K202400402"],"award-info":[{"award-number":["KJZD-K202400402"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,6,18]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Retinal vein occlusion (RVO), a common retinal vascular disease, is frequently treated with anti-vascular endothelial growth factor (anti-VEGF) agents as first-line therapy. However, anti-VEGF monotherapy lacks neuroprotective effects, primarily targets vascular leakage and neovascularisation, and requires frequent long-term injections that impose substantial economic burdens. Therefore, combined therapeutic strategies that address both vascular pathology and neural damage are being explored. This article describes the protocol for evaluating mecobalamin (a widely used neuroprotective drug) in combination with anti-VEGF for the treatment of macular edema (ME).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The study is a randomised, double-blind, placebo-controlled clinical trial that will enrol 120 patients with RVO from the First Affiliated Hospital of Chongqing Medical University. Participants will be randomly assigned (1:1) to an experimental group and a control group. The experimental group will receive intravitreal injections of conbercept plus oral mecobalamin for 6 months, while the control group will receive the same conbercept regimen plus a placebo for 6 months. All patients will undergo 1 year of follow-up after initial treatment, with visits at 1, 3, 6, 9 and 12 months. The primary outcome is the change in central subfield thickness from baseline to 1 year post initial treatment. Secondary outcomes consist of change in the best-corrected visual acuity from baseline over time, capillary density, cone photoreceptor distribution characteristics, mean light sensitivity and fixation stability, serum vitamin B12 levels, the number of treatments, frequency of injection (times per year), interval time, incidence and severity of adverse events (AEs) and serious AEs. Statistical analyses will use appropriate parametric and non-parametric tests for group comparisons, correlation analyses, and multivariate modelling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study has been approved by the Research Ethics Committee of The First Affiliated Hospital of Chongqing Medical University (No. 2025\u2013387-01). The results will be disseminated through conference presentations and publication in peer-reviewed international journals.<\/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=\"NCT07133438\">NCT07133438<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-111209","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T03:23:18Z","timestamp":1785122598000},"page":"e111209","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Adjuvant mecobalamin for anti-VEGF therapy in retinal vein occlusion: protocol of a single-centre, randomised, double-blinded controlled trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct07133438","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct07133438","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct07133438","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct07133438","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ke-Yu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China"},{"name":"Chongqing Key Laboratory of Prevention and Treatment of Major Blinding Diseases, Chongqing, People's Republic of China"},{"name":"Chongqing Eye Institute, Chongqing, People's Republic of China"},{"name":"Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, People's Republic of 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