{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:03:46Z","timestamp":1784099026420,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) activate antitumor immunity by targeting immune checkpoint molecules such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death receptor 1 (PD-1), and programmed death-ligand 1 (PD-L1). They have emerged as a key therapeutic modality for multiple malignancies. Nevertheless, excessive immune activation may trigger a spectrum of immune-related adverse events (irAEs). Though uncommon, uveitis is a sight-threatening irAEs that can result in permanent visual loss. The risk and prognostic outcomes of ICIs-associated uveitis remain poorly defined to date. Therefore, we performed this meta-analysis to systematically assess the correlation of ICIs therapy with uveitis risk and prognosis, with the goal of providing evidence-based recommendations for clinical identification and management of this ocular complication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Embase and Web of Science for cohort studies investigating the association between ICIs therapy and uveitis risk as well as prognosis. The search period was from the database inception to March 2026. The risk of bias of the included studies was assessed with the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). The meta-analysis was conducted using RevMan software.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, five studies comprising 277,790 participants were finally included. The meta-analysis revealed that ICIs therapy was associated with a significantly higher risk of uveitis (HR\u00a0=\u00a02.26, 95% CI: 1.46 - 3.51, P\u00a0=\u00a00.0003). However, no statistically significant association was observed between ICIs-associated uveitis and overall survival in the pooled analysis of two studies (HR\u00a0=\u00a00.69, 95% CI: 0.35 - 1.39, P\u00a0=\u00a00.30);this finding is based on limited evidence and should be interpreted with caution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Current evidence indicates that ICIs therapy was associated with an increased risk of uveitis. However, existing evidence regarding the impact of ICIs-associated uveitis on overall survival is of very low certainty and associated with a high risk of bias, which precludes drawing reliable conclusions. Large-scale prospective multicenter real-world cohort studies are therefore warranted. Such studies should implement standardized ophthalmological assessments and uniform outcome definitions, systematically record anatomical subtypes and severity grades of uveitis, and clarify the relationships between these subtypes\/grades and oncologic prognosis as well as systemic immune-related toxicity. Study outcomes should be reported stratified according to cancer type, and further research is required to explore biomarker-based risk prediction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261341882<\/jats:ext-link>\n                      , identifier CRD420261341882.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1833351","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:03:26Z","timestamp":1784095406000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between immune checkpoint inhibitors and the risk and prognosis of uveitis: a meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Qin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of TCM Comprehensive Treatment Area, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Aesthetic Medicine, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of TCM Comprehensive Treatment Area, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlian","family":"Mou","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnaf037","article-title":"Immune checkpoint inhibitors in high-grade gastroenteropancreatic neuroendocrine neoplasms","volume":"47","author":"Fazio","year":"2026","journal-title":"Endocr Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2026.104002","article-title":"Autoimmunity in the era of immune checkpoint inhibitors: The evolving epidemiology of autoimmune diseases and the possible impact of Covid-19","volume":"25","author":"Mahroum","year":"2026","journal-title":"Autoimmun Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1200\/jco-24-02776","article-title":"Long-term follow-up of real-world adjuvant anti-Pd-1 checkpoint inhibition and targeted therapy in patients with stage Iii melanoma","volume":"43","author":"Lodde","year":"2025","journal-title":"J Clin Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-013546","article-title":"Partitioned overall survival: Comprehensive analysis of survival states over 4 years in Checkmate 9er comparing first-line nivolumab plus cabozantinib versus sunitinib in advanced renal cell carcinoma","volume":"14","author":"Viray","year":"2026","journal-title":"J Immunother Cancer"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-2025-185","article-title":"A systematic review and network meta-analysis of immune checkpoint inhibitors in operable Nsclc: Neoadjuvant, adjuvant, or perioperative","volume":"14","author":"Petrelli","year":"2025","journal-title":"Transl Lung Cancer Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1111\/apt.70427","article-title":"Meta-analysis: Immune-related adverse events are\u00a0associated with improved effectiveness of immune checkpoint inhibitors in hepatocellular carcinoma","volume":"63","author":"Liu","year":"2026","journal-title":"Alimentary Pharmacol Ther"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-024-03212-z","article-title":"Impact of immune checkpoint inhibitors on vision and eye health","volume":"38","author":"Masalkhi","year":"2024","journal-title":"Eye (London England)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s12348-025-00484-8","article-title":"Immune checkpoint inhibitor-associated Vogt-Koyanagi-Harada-like syndrome: A descriptive systematic review","volume":"15","author":"Zhang","year":"2025","journal-title":"J Ophthalmic Inflammation Infection"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.18240\/ijo.2022.04.19","article-title":"Immune checkpoint inhibitor-associated ophthalmic adverse events: Current understanding of its mechanisms, diagnosis, and management","volume":"15","author":"Zhou","year":"2022","journal-title":"Int J Ophthalmol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12112547","article-title":"Emerging ocular side effects of immune checkpoint inhibitors: A comprehensive review","volume":"12","author":"Wu","year":"2024","journal-title":"Biomedicines"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2024.03.017","article-title":"Incident noninfectious uveitis risk after immune checkpoint inhibitor treatment","volume":"131","author":"Chang","year":"2024","journal-title":"Ophthalmology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ajo.2024.12.028","article-title":"Pathogenic mechanisms of immune checkpoint inhibitor (Ici)-associated retinal and choroidal adverse reactions","volume":"272","author":"Haliyur","year":"2025","journal-title":"Am J Ophthalmol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2024.08.044","article-title":"Ophthalmic immune-related adverse events and association with survival: Results from a real-world database","volume":"268","author":"Quiruz","year":"2024","journal-title":"Am J Ophthalmol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcjo.2025.02.010","article-title":"Association between immune checkpoint inhibitors and uveitis in patients with lung cancer, renal cell carcinoma, or Malignant melanoma","volume":"60","author":"Iwai","year":"2025","journal-title":"Can J Ophthalmol J Canadien d'Ophtalmologie"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1190001","article-title":"Association between immune-related adverse events and immunotherapy efficacy in non-small-cell lung cancer: A meta-analysis","volume":"14","author":"Lin","year":"2023","journal-title":"Front Pharmacol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1200\/jco.24.00191","article-title":"Corticosteroids for immune-related adverse events and checkpoint inhibitor efficacy: Analysis of six clinical trials","volume":"42","author":"Verheijden","year":"2024","journal-title":"J Clin Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2018.79.0006","article-title":"Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non-small-cell lung cancer","volume":"36","author":"Arbour","year":"2018","journal-title":"J Clin Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2021.02.003","article-title":"Updating guidance for reporting systematic reviews: Development of the Prisma 2020 statement","volume":"134","author":"Page","year":"2021","journal-title":"J Clin Epidemiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6215-8-16","article-title":"Practical methods for incorporating summary time-to-event data into meta-analysis","volume":"8","author":"Tierney","year":"2007","journal-title":"Trials"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/hm9.0000000000000093","article-title":"Efficacy and safety of acupuncture in treating low back and pelvic girdle pain during pregnancy: A systematic review and meta-analysis of randomized controlled trials","volume":"4","author":"Zhang","year":"2024","journal-title":"Acupuncture Herbal Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/HM9.0000000000000172","article-title":"Effectiveness of acupuncture in managing aromatase inhibitor-related arthralgia in breast cancer: A systematic review and meta-analysis","volume":"5","author":"Zhu","year":"2025","journal-title":"Acupuncture Herbal Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2025.11.001","article-title":"Immune checkpoint inhibitor-associated uveitis: Predictors and survival impact","volume":"10","author":"Chew","year":"2026","journal-title":"Ophthalmol Retina"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1302293","article-title":"Association between immune checkpoint inhibitor medication and uveitis: A population-based cohort study utilizing Trinetx database","volume":"14","author":"Kuo","year":"2023","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.584382","article-title":"Co-inhibitory receptor signaling in T-cell-mediated autoimmune glomerulonephritis","volume":"7","author":"Nagai","year":"2020","journal-title":"Front Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms262311619","article-title":"Beyond tumor immunity: The disruption of endocrine and infectious homeostasis by immune checkpoint inhibitors","volume":"26","author":"Sch\u00f6nberger","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.104808","article-title":"T cell-mediated mechanisms of immune-related adverse events induced by immune checkpoint inhibitors","volume":"213","author":"Li","year":"2025","journal-title":"Crit Rev Oncology\/Hematology"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2020.1773867","article-title":"Ocular\u00a0adverse events induced by immune checkpoint inhibitors: A comprehensive pharmacovigilance analysis","volume":"30","author":"Bomze","year":"2022","journal-title":"Ocular Immunol Inflammation"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12348-022-00321-2","article-title":"Ocular adverse events associated with immune checkpoint inhibitors, a scoping review","volume":"13","author":"Martens","year":"2023","journal-title":"J Ophthalmic Inflammation Infection"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1177\/1758835921992989","article-title":"Ocular adverse events associated with immune checkpoint inhibitors: A novel multidisciplinary management algorithm","volume":"13","author":"Shahzad","year":"2021","journal-title":"Ther Adv Med Oncol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics14030336","article-title":"Diagnosing and managing uveitis associated with immune checkpoint inhibitors: A review","volume":"14","author":"Zhang","year":"2024","journal-title":"Diagnostics (Basel)"},{"key":"B31","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1186\/s12886-020-01519-5","article-title":"Vogt-Koyanagi-Harada disease-like uveitis following nivolumab administration treated with steroid pulse therapy: A case report","volume":"20","author":"Kikuchi","year":"2020","journal-title":"BMC Ophthalmol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"39","DOI":"10.4103\/equest.equest_2_24","article-title":"Immunosuppressives and beyond: Newer advances in the treatment of uveitis","volume":"48","author":"Kumar","year":"2023","journal-title":"EyeQuest"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1703382","article-title":"Breach and restoration of retinal immune privilege: Barrier failure, innate dysregulation, and adaptive autoimmunity","volume":"16","author":"Fan","year":"2025","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1186\/s13619-025-00228-y","article-title":"Preserving blood-retinal barrier integrity: A path to retinal ganglion cell protection in glaucoma and traumatic optic neuropathy","volume":"14","author":"Zhou","year":"2025","journal-title":"Cell Regeneration (London England)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.13389\/j.cnki.rao.2022.0205","article-title":"Research progress of drug-induced uveitis caused\u00a0by\u00a0anti-programmed cell death receptor-1\/programmed cell death ligand-1 monoclonal antibodies","volume":"42","author":"Zhu","year":"2022","journal-title":"Recent Adv Ophthalmol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1833351\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:03:28Z","timestamp":1784095408000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1833351\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2026.1833351"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1833351","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"article-number":"1833351"}}