{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:41:38Z","timestamp":1786545698335,"version":"build-2736575974"},"reference-count":49,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"unspecified","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2033906"],"award-info":[{"award-number":["2033906"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,7,27]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Anterior uveitis is an intraocular inflammatory condition that can lead to vision impairment without appropriate and timely treatment. Determining its aetiology can be difficult due to its heterogeneous clinical presentations, which challenges effective treatment. The primary aim of this systematic review is to comprehensively identify and synthesise evidence on the immunological features of anterior uveitis in the human cornea and tear film, as a foundation for considering the utility of such features as biomarkers for disease classification, prognosis and monitoring treatment responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Comprehensive electronic database searches will be performed in Ovid MEDLINE, Ovid Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) without date restrictions. Two independent review authors will screen retrieved titles and abstracts in Covidence relative to predefined study eligibility criteria. Studies judged eligible or potentially eligible for inclusion will undergo full-text review using a similar method. Disagreements will be resolved by consensus. For each included study, risk of bias will be assessed using validated tools appropriate to the study design. Where sufficient and appropriate data are available, meta-analyses will be performed. For outcomes where a meta-analysis is not possible, a narrative synthesis will be provided. This review will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethics approval is not applicable for this review as no original data will be collected. The results of this review are expected to be disseminated through a peer-reviewed publication and\/or scientific conference presentations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD420261339682.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-121276","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:45:18Z","timestamp":1786542318000},"page":"e121276","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Corneal and tear film immunology in anterior uveitis: protocol for a systematic review and meta-analysis"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2434-8055","authenticated-orcid":false,"given":"Jessie L","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8485-7575","authenticated-orcid":false,"given":"Ching Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2871-7764","authenticated-orcid":false,"given":"Alexander S","family":"Fraser","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Southend University Hospital, Westcliff-on-Sea, Essex, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5422-040X","authenticated-orcid":false,"given":"Myra B","family":"McGuinness","sequence":"additional","affiliation":[{"name":"Centre for Eye Research Australia Ltd, Melbourne, Victoria, Australia"},{"name":"Department of Surgery (Ophthalmology), Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2491-685X","authenticated-orcid":false,"given":"Lyndell L","family":"Lim","sequence":"additional","affiliation":[{"name":"Centre for Eye Research Australia Ltd, Melbourne, Victoria, Australia"},{"name":"Department of Surgery (Ophthalmology), Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1596-2259","authenticated-orcid":false,"given":"Laura E","family":"Downie","sequence":"additional","affiliation":[{"name":"Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2026081206450896000_16.8.e121276.1","doi-asserted-by":"publisher","DOI":"10.1080\/09286586.2021.1882506"},{"key":"2026081206450896000_16.8.e121276.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.07.007"},{"key":"2026081206450896000_16.8.e121276.3","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2003.037226"},{"key":"2026081206450896000_16.8.e121276.4","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.80.4.332"},{"key":"2026081206450896000_16.8.e121276.5","first-page":"1","article-title":"Epidemiology of uveitis","volume":"45","author":"Chang","year":"2005","journal-title":"Int Ophthalmol Clin"},{"key":"2026081206450896000_16.8.e121276.6","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jcjo.2024.07.013","article-title":"Anterior uveitis for the comprehensive ophthalmologist","volume":"60","author":"Xie","year":"2025","journal-title":"Canadian Journal of Ophthalmology"},{"key":"2026081206450896000_16.8.e121276.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2021.03.061"},{"key":"2026081206450896000_16.8.e121276.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2005.03.057"},{"key":"2026081206450896000_16.8.e121276.9","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2019.1640883"},{"key":"2026081206450896000_16.8.e121276.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2008.06.004"},{"key":"2026081206450896000_16.8.e121276.11","doi-asserted-by":"crossref","DOI":"10.1167\/iovs.17-21788","article-title":"Biomarkers and Surrogate Endpoints in Uveitis: The Impact of Quantitative Imaging","volume":"58","author":"Denniston","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2026081206450896000_16.8.e121276.12","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-89794-0","article-title":"Development of fully automated anterior chamber cell analysis based on image software","volume":"11","author":"Kang","year":"2021","journal-title":"Sci Rep"},{"key":"2026081206450896000_16.8.e121276.13","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1080\/09273948.2019.1709650","article-title":"Non-invasive Instrument-Based Tests for Quantifying Anterior Chamber Flare in Uveitis: A Systematic Review","volume":"29","author":"Liu","year":"2021","journal-title":"Ocul Immunol Inflamm"},{"key":"2026081206450896000_16.8.e121276.14","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11237034","article-title":"Tear and Plasma Levels of Cytokines in Patients with Uveitis: Search for Active Disease Biomarkers","volume":"11","author":"Garc\u00eda-Onrubia","year":"2022","journal-title":"J Clin Med"},{"key":"2026081206450896000_16.8.e121276.15","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1007\/s00417-020-04707-7","article-title":"Tear cytokines as potential biomarkers in non-infectious uveitis: post hoc analysis of a randomised clinical trial","volume":"258","author":"Shirinsky","year":"2020","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"2026081206450896000_16.8.e121276.16","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1080\/09273948.2020.1836236","article-title":"Keratic Precipitates: The Underutilized Diagnostic Clue","volume":"29","author":"Chan","year":"2021","journal-title":"Ocul Immunol Inflamm"},{"key":"2026081206450896000_16.8.e121276.17","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.122.12.1773"},{"key":"2026081206450896000_16.8.e121276.18","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1080\/09273948.2017.1298818","article-title":"In Vivo Laser Confocal Microscopy Using the HRT-Rostock Cornea Module: Diversity and Diagnostic Implications in Patients with Uveitis","volume":"26","author":"Lim","year":"2018","journal-title":"Ocul Immunol Inflamm"},{"key":"2026081206450896000_16.8.e121276.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2009.07.016"},{"key":"2026081206450896000_16.8.e121276.20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/ICO.0b013e3181acf674","article-title":"Confocal scan features of keratic precipitates in Fuchs heterochromic iridocyclitis","volume":"29","author":"Kanavi","year":"2010","journal-title":"Cornea"},{"key":"2026081206450896000_16.8.e121276.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2006.07.040"},{"key":"2026081206450896000_16.8.e121276.22","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2015-307429"},{"key":"2026081206450896000_16.8.e121276.23","doi-asserted-by":"crossref","DOI":"10.1186\/s12348-014-0031-y","article-title":"Frequency of dendritiform inflammatory cells in the cornea in herpetic anterior uveitis without clinical keratitis and Fuchs uveitis","volume":"4","author":"Knoll","year":"2014","journal-title":"J Ophthalmic Inflamm Infect"},{"key":"2026081206450896000_16.8.e121276.24","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2217795120","article-title":"Redefining the human corneal immune compartment using dynamic intravital imaging","volume":"120","author":"Downie","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026081206450896000_16.8.e121276.25","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1038\/s41433-023-02426-x","article-title":"Increased dendritic cell density and altered morphology in allergic conjunctivitis","volume":"37","author":"Tajbakhsh","year":"2023","journal-title":"Eye (Lond)"},{"key":"2026081206450896000_16.8.e121276.26","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1097\/ICO.0000000000001014","article-title":"Translational Immunoimaging and Neuroimaging Demonstrate Corneal Neuroimmune Crosstalk","volume":"35 Suppl 1","author":"Hamrah","year":"2016","journal-title":"Cornea"},{"key":"2026081206450896000_16.8.e121276.27","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/ceo.13972","article-title":"Corneal immune cell morphometry as an indicator of local and systemic pathology: A review","volume":"49","author":"Chinnery","year":"2021","journal-title":"Clinical Exper Ophthalmology"},{"key":"2026081206450896000_16.8.e121276.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2006.06.057"},{"key":"2026081206450896000_16.8.e121276.29","doi-asserted-by":"crossref","first-page":"7179","DOI":"10.1167\/iovs.15-17433","article-title":"Corneal Epithelial Immune Dendritic Cell Alterations in Subtypes of Dry Eye Disease: A Pilot In Vivo Confocal Microscopic Study","volume":"56","author":"Kheirkhah","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2026081206450896000_16.8.e121276.30","doi-asserted-by":"crossref","first-page":"6277","DOI":"10.1364\/BOE.536553","article-title":"Improved tracking of corneal immune cell dynamics using in vivo confocal microscopy","volume":"15","author":"Bedggood","year":"2024","journal-title":"Biomed Opt Express"},{"key":"2026081206450896000_16.8.e121276.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.03.006"},{"key":"2026081206450896000_16.8.e121276.32","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2020.1758731"},{"key":"2026081206450896000_16.8.e121276.33","doi-asserted-by":"crossref","first-page":"e405","DOI":"10.1111\/aos.13292","article-title":"Cytokine and chemokine tear levels in patients with uveitis","volume":"95","author":"Carre\u00f1o","year":"2017","journal-title":"Acta Ophthalmol"},{"key":"2026081206450896000_16.8.e121276.34","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1080\/09273948.2019.1704022","article-title":"Tear IL-6 and IL-10 levels in HLA-B27-Associated Uveitis and Its clinical Implications","volume":"29","author":"Kumar","year":"2021","journal-title":"Ocul Immunol Inflamm"},{"key":"2026081206450896000_16.8.e121276.35","doi-asserted-by":"crossref","DOI":"10.1186\/s12348-018-0156-5","article-title":"Discovery of tear biomarkers in children with chronic non-infectious anterior uveitis: a pilot study","volume":"8","author":"Angeles-Han","year":"2018","journal-title":"J Ophthalmic Inflamm Infect"},{"key":"2026081206450896000_16.8.e121276.36","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3390\/publications10030021","article-title":"Research Questions with PICO: A Universal Mnemonic","volume":"10","author":"Nishikawa-Pacher","year":"2022","journal-title":"Publications"},{"key":"2026081206450896000_16.8.e121276.37","doi-asserted-by":"crossref","DOI":"10.1167\/iovs.66.12.23","article-title":"Altered Corneal T-Cell Motility and Sensory Nerve Features in Older Adults With Human Immunodeficiency Virus Infection","volume":"66","author":"Karunaratne","year":"2025","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2026081206450896000_16.8.e121276.38","doi-asserted-by":"crossref","unstructured":"Higgins JP , Savovi\u0107 J , Page MJ , et al . Assessing risk of bias in a randomized trial. In: Cochrane Handbook for Systematic Reviews of Interventions. 2019: 205\u201328.","DOI":"10.1002\/9781119536604.ch8"},{"key":"2026081206450896000_16.8.e121276.39","unstructured":"Stearne J , Higgins J , ROBINS-I Development Group . Risk of bias in non-randomized studies\u2013of interventions, version 2 (ROBINS-I V2). 2025. Available: https:\/\/www.riskofbias.info\/welcome\/robins-i-v2"},{"key":"2026081206450896000_16.8.e121276.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2024.108602"},{"key":"2026081206450896000_16.8.e121276.41","unstructured":"Study quality assessment tools: National Institute of Health. 2021. Available: https:\/\/www.nhlbi.nih.gov\/health-topics\/study-quality-assessment-tools"},{"key":"2026081206450896000_16.8.e121276.42","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"2026081206450896000_16.8.e121276.43","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyn204"},{"key":"2026081206450896000_16.8.e121276.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.12.039"},{"key":"2026081206450896000_16.8.e121276.45","first-page":"S248","article-title":"Recurrent and chronic anterior uveitis: Long-term outcome and treatment strategies","volume":"72","author":"Sharon","year":"2024","journal-title":"Indian J Ophthalmol (Poona City)"},{"key":"2026081206450896000_16.8.e121276.46","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1016\/j.ophtha.2011.02.044","article-title":"Risk of relapse in primary acute anterior uveitis","volume":"118","author":"Grunwald","year":"2011","journal-title":"Ophthalmology"},{"key":"2026081206450896000_16.8.e121276.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2017.03.029"},{"key":"2026081206450896000_16.8.e121276.48","doi-asserted-by":"crossref","unstructured":"Khadamy J , Rani S . Diagnostic and therapeutic strategies in uveitis: a clinical approach. In: Khadamy J , ed. Uveitis in the Clinic - Current Approaches and Future Directions in Diagnosis, Treatment, and Patient Care. London: IntechOpen, 2025.","DOI":"10.5772\/intechopen.1006762"},{"key":"2026081206450896000_16.8.e121276.49","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1080\/09286586.2020.1856385","article-title":"The Impact of Adult Uveitis on Quality of Life: An Exploratory Study","volume":"28","author":"Prem Senthil","year":"2021","journal-title":"Ophthalmic Epidemiol"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2026-121276","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:45:23Z","timestamp":1786542323000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2026-121276"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":49,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,12]]},"published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1136\/bmjopen-2026-121276"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2026-121276","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]}}}