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Aqueous humour (AqH) was collected immediately before intravitreal bevacizumab, ranibizumab or aflibercept injections from patients with RVO. We included an acute group (RVO onset within 3 months) and a recurrent group (patients with disease duration of \u2265\u20091 year). Using a multiplex cytokine assay, we measured the concentrations of nine cytokines and VEGF. The results were compared with controls after adjusting for sex, age, axial length, and posterior vitreous detachment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AqH samples from 30 acute branch RVO (BRVO), 31 recurrent BRVO, 25 acute central RVO (CRVO), 20 recurrent CRVO, and 81 cataract surgery eyes without retinal disease (as controls) were used. In recurrent BRVO, MCP-1, CXCL13, and CCL11 levels were significantly lower than those in control eyes (all,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). Similarly, in recurrent CRVO, MCP-1, CXCL12, CXCL13, CCL11, and CXCL1 levels were significantly reduced compared with controls (all,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05), whereas IL-6 levels were significantly elevated (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05).\u3000In acute RVO, cytokine alterations compared with controls were limited. Acute BRVO showed decreased MCP-1, CXCL13, and CCL11 levels (all,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05), while acute CRVO exhibited increased IL-6 and IP-10 levels (all,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Inflammatory cytokine profiles in recurrent RVO differ between BRVO and CRVO and are characterized by reduced levels of multiple inflammatory cytokines compared with controls. These findings highlight distinct inflammatory features of recurrent RVO and provide a basis for future studies investigating disease progression and treatment resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      UMIN000020718\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/center6.umin.ac.jp\/cgi-open-bin\/icdr_e\/ctr_his_list.cgi?recptno=R000023907\" ext-link-type=\"uri\">https:\/\/center6.umin.ac.jp\/cgi-open-bin\/icdr_e\/ctr_his_list.cgi?recptno=R000023907<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key messages<\/jats:title>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>What is known<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>While anti- endothelial growth factor (VEGF) therapy is effective for treating cystic macular oedema (CME) secondary to retinal vein occlusion (RVO), the condition is not confined to the acute phase. The frequent chronicity and recurrence of CME imply that other pathological factors, beyond VEGF, are involved. Furthermore, preceding research on acute RVO has documented increased levels of inflammatory cytokines, including IL-6, IL-8, and MCP-1.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>What is new<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Inflammatory cytokine profiles differ between branch RVO and central RVO in both acute and recurrent cases when each is explained relative to controls using multivariable-adjusted analyses. In particular, recurrent RVO is characterized by reduced levels of several inflammatory cytokines compared with controls, indicating a distinct inflammatory profile in the recurrent phase and providing insights into disease progression.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00417-026-07152-0","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:10:45Z","timestamp":1771654245000},"page":"1833-1842","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aqueous humour cytokine profiles in retinal vein occlusion: a comparative study of acute, chronic recurrent, and control eyes"],"prefix":"10.1007","volume":"264","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-8169","authenticated-orcid":false,"given":"Satoru","family":"Inoda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5331-4730","authenticated-orcid":false,"given":"Hidenori","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4138-3568","authenticated-orcid":false,"given":"Chihiro","family":"Mayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiro","family":"Fujino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Kawashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1132-6148","authenticated-orcid":false,"given":"Toshikatsu","family":"Kaburaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9159-7329","authenticated-orcid":false,"given":"Yasuo","family":"Yanagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"key":"7152_CR1","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/mt.2008.10","volume":"16","author":"PA Campochiaro","year":"2008","unstructured":"Campochiaro PA, Hafiz G, Shah SM et al (2008) Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. 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Satoru Inoda declares lecturer\u2019s fees from Kowa, Novartis, Bayer, Santen, Chugai, and DeepEyeVision, Inc., and grants from Novartis outside this work. Hidenori Takahashi was a founder of DeepEyeVision, Inc., and declares patents outside this work, lecturer\u2019s fees from Santen, Kowa, Senju, Novartis, and Bayer outside this work, and grants from Senju, Novartis and Bayer outside this work. Shinichi Sakamoto declares lecturer\u2019s fees from Chugai, outside this work. Hidetoshi Kawashima declares lecturer\u2019s fees from Otsuka, Senju, Mitsubishi-Tanabe, Kowa, Santen, Novartis and Zeiss outside this work and grants from Senju, Linical, DeepEyeVision, HOYA, Santen, Heiwa-Iyou, and Bayer outside this work. Yasuo Yanagi declares grants from Santen and Novartis outside this work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}