{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:25:36Z","timestamp":1777861536555,"version":"3.51.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study examined the association between vitreous cellular repressor of E1A-stimulated genes 1 (CREG1) levels and the therapeutic response to ranibizumab in patients with diabetic macular edema (DME).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this retrospective study, 189 DME patients receiving ranibizumab were categorized into responders (\n                      <jats:italic>n<\/jats:italic>\n                      = 158) and non-responders (\n                      <jats:italic>n<\/jats:italic>\n                      = 31) based on edema resolution. Clinical variables and vitreous CREG1 levels were analyzed. LASSO regression and multivariate logistic models identified factors influencing treatment response. Patients were followed for 12 months, with central macular thickness (CMT), retinal nerve fiber layer (RNFL) thickness, and best-corrected visual acuity (BCVA) compared between groups and correlated with CREG1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Non-responders had a higher prevalence of serous retinal detachment and elevated HbA1c, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), but lower CREG1 and estimated glomerular filtration rate (eGFR) (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). LASSO-selected factors (CREG1, OCT classification, HbA1c, NLR, PLR, eGFR) were analyzed by logistic regression: OCT class, HbA1c, NLR, and PLR were risk factors for non-response, whereas CREG1 and eGFR were protective factors (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). Throughout follow-up, non-responders exhibited worse BCVA, greater CMT, and thicker RNFL (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). Vitreous CREG1 was negatively correlated with CMT, RNFL, and BCVA at all timepoints (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Lower vitreous CREG1 is associated with poor response to ranibizumab in DME. CREG1, along with OCT features, HbA1c, NLR, PLR, and eGFR, significantly influences treatment outcomes and correlates with long-term anatomical and visual prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1804072","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:24:21Z","timestamp":1777523061000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of vitreous CREG1 with diabetic macular edema response and edema resolution following ranibizumab therapy"],"prefix":"10.3389","volume":"13","author":[{"given":"Linling","family":"Zhu","sequence":"first","affiliation":[{"name":"Lixiang Eye Hospital of Soochow University, Suzhou","place":["Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmei","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Huizhou Hospital of Traditional Chinese Medicine, Huizhou","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixiang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Lixiang Eye Hospital of Soochow University, Suzhou","place":["Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Cao","sequence":"additional","affiliation":[{"name":"Lixiang Eye Hospital of Soochow University, Suzhou","place":["Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danni","family":"Li","sequence":"additional","affiliation":[{"name":"Lixiang Eye Hospital of Soochow University, Suzhou","place":["Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Cao","sequence":"additional","affiliation":[{"name":"Lixiang Eye Hospital of Soochow University, Suzhou","place":["Jiangsu, 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