{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:06:02Z","timestamp":1790186762121,"version":"4.1.0"},"reference-count":19,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the anatomical and functional outcomes of faricimab in the treatment of na\u00efve and refractory diabetic macular edema (DME) and to investigate OCT biomarkers associated with visual outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective real-world study included eyes with DME treated with faricimab. All eyes received three loading injections followed by a treat-and-extend regimen. The primary outcomes were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT). Secondary outcomes included changes in OCT biomarkers, including intraretinal cysts (IRCs), subretinal fluid (SRF), hyperreflective foci (HRFs), disorganization of the retinal inner layers (DRIL), and external limiting membrane\/ellipsoid zone (ELM\/EZ) disruption. Changes in BCVA, CMT, and OCT biomarkers were analyzed using generalized estimating equations (GEEs). A multivariable GEE model was used to identify factors independently associated with 12-month BCVA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 110 eyes from 104 patients were included. At 12 months, the CMT significantly decreased in both the na\u00efve and refractory groups (both P\u2009&lt;\u20090.001). BCVA significantly improved in na\u00efve eyes (P\u2009=\u20090.003), whereas visual improvement was limited in refractory eyes (P\u2009=\u20090.390). Both groups showed significant reductions in the proportions of eyes with IRCs, SRF, and HRFs (all P\u2009&lt;\u20090.001). Refractory eyes had higher proportions of baseline DRIL and ELM\/EZ disruption (both P\u2009&lt;\u20090.001). In the multivariable GEE model, baseline DRIL (B\u2009=\u20090.044; 95% CI: 0.004 to 0.084; P\u2009=\u20090.031) and ELM\/EZ disruption (B\u2009=\u20090.147; 95% CI: 0.069 to 0.225; P\u2009&lt;\u20090.001) remained independently associated with poor 12-month BCVA, whereas the treatment group was not independently associated with 12-month BCVA (P\u2009=\u20090.969).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Faricimab achieved effective retinal fluid control in both na\u00efve and refractory DME. However, visual recovery was associated with baseline retinal microstructural integrity, with DRIL and ELM\/EZ disruption independently associated with poorer 12-month visual outcomes beyond conventional anatomical parameters. In eyes with refractory DME and limited visual improvement, sustained fluid control and reduced treatment burden may remain clinically meaningful outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0358993","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:38:37Z","timestamp":1790185117000},"page":"e0358993","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Use of faricimab for refractory diabetic macular edema in real-world clinical practice: When anatomical success meets functional limits"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1964-7325","authenticated-orcid":true,"given":"Zheyao","family":"Gu","sequence":"first","affiliation":[{"name":"The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital","place":["Suzhou, China"],"department":["Department of Ophthalmology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xi","sequence":"additional","affiliation":[{"name":"The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital","place":["Suzhou, China"],"department":["Department of Ophthalmology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangying","family":"Luo","sequence":"additional","affiliation":[{"name":"The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital","place":["Suzhou, China"],"department":["Department of Ophthalmology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"issue":"4","key":"pone.0358993.ref001","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000458539","article-title":"Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA)","volume":"237","author":"U Schmidt-Erfurth","year":"2017","journal-title":"Ophthalmologica"},{"key":"pone.0358993.ref002","doi-asserted-by":"crossref","first-page":"1699271","DOI":"10.3389\/fcell.2025.1699271","article-title":"Microglia response and function in a chronic model of photoreceptor damage","volume":"13","author":"D Raghavan","year":"2025","journal-title":"Front Cell Dev Biol"},{"issue":"10326","key":"pone.0358993.ref003","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0140-6736(22)00018-6","article-title":"Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): Two randomised, double-masked, phase 3 trials","volume":"399","author":"CC Wykoff","year":"2022","journal-title":"Lancet"},{"issue":"17","key":"pone.0358993.ref004","doi-asserted-by":"crossref","first-page":"8481","DOI":"10.3390\/ijms26178481","article-title":"Serum vitamin D levels as predictors of response to intravitreal anti-VEGF therapy in diabetic macular edema: A clinical correlation study","volume":"26","author":"N Dervis","year":"2025","journal-title":"Int J Mol Sci"},{"key":"pone.0358993.ref005","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1007\/s13300-022-01326-9","article-title":"The role of angiopoietins in neovascular diabetes-related retinal diseases","volume":"13","author":"JD Collazos-Alem\u00e1n","year":"2022","journal-title":"Diabetes Ther"},{"issue":"5","key":"pone.0358993.ref006","doi-asserted-by":"crossref","first-page":"896","DOI":"10.3390\/medicina59050896","article-title":"Pathological neurovascular unit mapping onto multimodal imaging in diabetic macular edema","volume":"59","author":"T Murakami","year":"2023","journal-title":"Medicina (Kaunas)"},{"key":"pone.0358993.ref007","doi-asserted-by":"crossref","first-page":"269","DOI":"10.2147\/OPTH.S502033","article-title":"Clinical evaluation of faricimab in real-world diabetic 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patients with diabetic macular edema following a therapy switch to faricimab","volume":"13","author":"P Wolfrum","year":"2024","journal-title":"J Clin Med"},{"issue":"5","key":"pone.0358993.ref011","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1167\/iovs.65.5.26","article-title":"Intraretinal hyper-reflective foci are almost universally present and co-localize with intraretinal fluid in diabetic macular edema","volume":"65","author":"EL von Schulthess","year":"2024","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"pone.0358993.ref012","doi-asserted-by":"crossref","DOI":"10.1136\/bmjophth-2025-002415","article-title":"6-month outcomes of intravitreal faricimab injection for neovascular age-related macular degeneration and their relationships with clinical findings: A multicentre cohort study from the J-CREST","volume":"10","author":"R Yanai","year":"2025","journal-title":"BMJ Open Ophthalmol"},{"key":"pone.0358993.ref013","first-page":"8164250","article-title":"Role of inflammation in classification of diabetic macular edema by optical coherence tomography","volume":"2019","author":"Y-R Chung","year":"2019","journal-title":"J Diabetes Res"},{"issue":"5","key":"pone.0358993.ref014","doi-asserted-by":"crossref","first-page":"100798","DOI":"10.1016\/j.xops.2025.100798","article-title":"Effect of faricimab versus aflibercept on hyperreflective foci in patients with diabetic macular edema from the YOSEMITE\/RHINE trials","volume":"5","author":"U Chakravarthy","year":"2025","journal-title":"Ophthalmol Sci"},{"issue":"6","key":"pone.0358993.ref015","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.3390\/medicina59061125","article-title":"Faricimab for diabetic macular edema in patients refractory to ranibizumab or aflibercept","volume":"59","author":"H Ohara","year":"2023","journal-title":"Medicina 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diabetic macular edema: A systematic review","volume":"71","author":"K Nanji","year":"2026","journal-title":"Surv Ophthalmol"},{"issue":"1","key":"pone.0358993.ref019","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ophtha.2025.07.038","article-title":"Baseline OCT biomarkers associated with visual acuity in diabetic macular edema: A systematic review and meta-analysis","volume":"133","author":"K Nanji","year":"2026","journal-title":"Ophthalmology"}],"container-title":["PLOS 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