{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:01:14Z","timestamp":1790776874158,"version":"4.1.0"},"reference-count":47,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"unspecified","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,9,21]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the clinical severity of dry eye disease and its association with tear film inflammatory biomarkers among adults in Northern Ethiopia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Multicentre cross-sectional study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Ophthalmic centres in Northern Ethiopia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>A total of 618 adults were included in the analysis, with a response rate of 97.17%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sociodemographic and clinical data were collected using a pretested structured questionnaire. Dry eye disease was assessed using the Ocular Surface Disease Index, tear break-up time, Schirmer I test and ocular surface staining. Tear samples were collected and analysed for interleukin (IL)-1\u03b2, IL-6, tumour necrosis factor-alpha (TNF-\u03b1) and matrix metalloproteinase-9 (MMP-9) using standard laboratory procedures. Differences in biomarker concentrations across dry eye disease severity categories were assessed using one-way analysis of variance or appropriate non-parametric tests. Correlations between inflammatory biomarkers and clinical parameters were assessed using Pearson or Spearman correlation coefficients, as appropriate. Ordinal multivariable logistic regression was used to identify factors associated with increasing dry eye disease severity. Statistical significance was set at p&lt;0.05.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The prevalence of dry eye disease was 44.01% (95% CI 40.8% to 48.1%). Concentrations of IL-1\u03b2, IL-6, TNF-\u03b1 and MMP-9 increased significantly across dry eye disease severity categories. MMP-9 demonstrated the strongest correlations with clinical parameters of DED. Female sex (adjusted OR (AOR)=1.62, 95%\u2009CI 1.15 to 2.30), diabetes mellitus (AOR=2.18; 95%\u2009CI 1.34 to 3.55), screen exposure of \u22653\u2009hours\/day (AOR=2.12; 95%\u2009CI 1.48 to 3.04), bicycle or motorbike riding (AOR=1.69; 95%\u2009CI 1.16 to 2.46)\u2009and alcohol consumption (AOR=1.58; 95%\u2009CI 1.06 to 2.35) were independently associated with increasing dry eye disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dry eye disease was common among adults attending ophthalmic centres in Northern Ethiopia, with inflammatory biomarker concentrations increasing with greater clinical severity. MMP-9 showed the strongest observed association with clinical measures of dry eye disease. These findings suggest that tear film inflammatory biomarkers may have relevance for understanding the biological processes underlying dry eye disease severity, while attention to modifiable associated factors may contribute to improved prevention and management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-121775","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:35:42Z","timestamp":1790775342000},"page":"e121775","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical severity of dry eye disease and its association with tear film inflammatory biomarkers among adults in Northern Ethiopia: A multicentre cross-sectional study"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8504-182X","authenticated-orcid":false,"given":"Yitayal Abebe","family":"Gudayneh","sequence":"first","affiliation":[{"name":"Ophthalmology, Boru Meda General Hospital, Dessie, Amhara, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alemnew Taye","family":"Dires","sequence":"additional","affiliation":[{"name":"Internal Medicine, Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Amhara, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damtie Lankir","family":"Abebe","sequence":"additional","affiliation":[{"name":"Public Health Emergency Directorate, Amhara Public Health Institute, Bahir Dar, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2881-807X","authenticated-orcid":false,"given":"Abebech Tewabe","family":"Gelaye","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy, Bahir Dar University College of Medicine and Health Science, Bahir Dar, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahlet Gubena","family":"Hailu","sequence":"additional","affiliation":[{"name":"College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5596-3677","authenticated-orcid":false,"given":"Getachew Kassahun","family":"Desalegn","sequence":"additional","affiliation":[{"name":"Department of Optometry, University of Gondar College of Medicine and Health Sciences, Gondar, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simegnew Tilahun","family":"Amlaku","sequence":"additional","affiliation":[{"name":"School of Public Health, Debre Tabor University College of Health Sciences, Debre Tabor, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2539-3755","authenticated-orcid":false,"given":"Sisay Eshete","family":"Tadesse","sequence":"additional","affiliation":[{"name":"Nutrition and Dietetics, Wollo University, Dessie, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"2026093006350980000_16.9.e121775.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.008"},{"key":"2026093006350980000_16.9.e121775.2","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s00210-025-04454-8","article-title":"Which topical ophthalmic drugs work best for Keratoconjunctivitis Sicca? A systematic review and meta-analysis","volume":"399","author":"Chen","year":"2026","journal-title":"Naunyn-Schmiedeberg's Arch Pharmacol"},{"key":"2026093006350980000_16.9.e121775.3","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.jtos.2017.05.003","article-title":"TFOS DEWS II Epidemiology Report","volume":"15","author":"Stapleton","year":"2017","journal-title":"Ocul Surf"},{"key":"2026093006350980000_16.9.e121775.4","doi-asserted-by":"crossref","first-page":"102438","DOI":"10.1016\/j.clae.2025.102438","article-title":"How effective and safe are punctal plugs in treating dry eye disease? A systematic review and meta-analysis","volume":"48","author":"Chen","year":"2025","journal-title":"Cont Lens Anterior Eye"},{"key":"2026093006350980000_16.9.e121775.5","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.21608\/ejhc.2024.380825","article-title":"Dry Eyes Related Quality of Life in Elderly Patients with Meibomian Gland Dysfunction at Zagazig University Hospitals","volume":"15","author":"Abdelrahman Ahmed","year":"2024","journal-title":"Egyptian J Health Care"},{"key":"2026093006350980000_16.9.e121775.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.03.006"},{"key":"2026093006350980000_16.9.e121775.7","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul Surf"},{"key":"2026093006350980000_16.9.e121775.8","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1007\/s13273-025-00583-6","article-title":"Protective effects of XanMax\u00ae 2002 on ocular surface damage in dry eye disease: evidence from animal and cell models","volume":"21","author":"Kim","year":"2025","journal-title":"Mol Cell Toxicol"},{"key":"2026093006350980000_16.9.e121775.9","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.2147\/OPTH.S532001","article-title":"Oxidative Stress in Dry Eye Disease: A Bibliometric Analysis","volume":"19","author":"Lei","year":"2025","journal-title":"Clin Ophthalmol"},{"key":"2026093006350980000_16.9.e121775.10","doi-asserted-by":"publisher","DOI":"10.4103\/tjo.tjo_56_19"},{"key":"2026093006350980000_16.9.e121775.11","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/aos.13436","article-title":"Clinical impact of inflammation in dry eye disease: proceedings of the ODISSEY group meeting","volume":"96","author":"Baudouin","year":"2018","journal-title":"Acta Ophthalmol (Copenh)"},{"key":"2026093006350980000_16.9.e121775.12","doi-asserted-by":"crossref","first-page":"140","DOI":"10.33791\/2222-4408-2025-2-140-147","article-title":"Changes in tear fluid composition in dry eye disease: a literature review","volume":"27","author":"Chesnokova","year":"2025","journal-title":"The EYE GLAZ."},{"key":"2026093006350980000_16.9.e121775.13","doi-asserted-by":"publisher","DOI":"10.1111\/aos.13526"},{"key":"2026093006350980000_16.9.e121775.14","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.2147\/OPTH.S433679","article-title":"Symptomatic Dry Eye Disease and Associated Factors Among Adult Diabetic Patients in Adare General Hospital","volume":"17","author":"Bekele","year":"2023","journal-title":"Clin Ophthalmol"},{"key":"2026093006350980000_16.9.e121775.15","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.118.5.615"},{"key":"2026093006350980000_16.9.e121775.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.001"},{"key":"2026093006350980000_16.9.e121775.17","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1001\/jamaophthalmol.2013.561","article-title":"Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye","volume":"131","author":"Sambursky","year":"2013","journal-title":"JAMA Ophthalmol"},{"key":"2026093006350980000_16.9.e121775.18","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.118.5.615"},{"key":"2026093006350980000_16.9.e121775.19","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1016\/j.ophtha.2016.07.028","article-title":"Matrix Metalloproteinase 9 Testing in Dry Eye Disease Using a Commercially Available Point-of-Care Immunoassay","volume":"123","author":"Messmer","year":"2016","journal-title":"Ophthalmology"},{"key":"2026093006350980000_16.9.e121775.20","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/cxo.12918","article-title":"Tear film, contact lenses and tear biomarkers","volume":"102","author":"Willcox","year":"2019","journal-title":"Clin Exp Optom"},{"key":"2026093006350980000_16.9.e121775.21","doi-asserted-by":"crossref","first-page":"411","DOI":"10.2147\/OPTH.S125364","article-title":"Cytokine biomarkers in tear film for primary open-angle glaucoma","volume":"11","author":"Gupta","year":"2017","journal-title":"Clin Ophthalmol"},{"key":"2026093006350980000_16.9.e121775.22","doi-asserted-by":"publisher","DOI":"10.4103\/IJO.IJO_2981_22"},{"key":"2026093006350980000_16.9.e121775.23","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2024-090721","article-title":"Symptomatic dry eye disease and its associated factors among adult patients with diabetes attending comprehensive specialised hospitals in Amhara Region, Ethiopia: a multicentre institution-based cross-sectional study","volume":"15","author":"Shumye","year":"2025","journal-title":"BMJ Open"},{"key":"2026093006350980000_16.9.e121775.24","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.clae.2016.06.008","article-title":"Dry eye disease in an adult population in South-West Nigeria","volume":"39","author":"Olaniyan","year":"2016","journal-title":"Cont Lens Anterior Eye"},{"key":"2026093006350980000_16.9.e121775.25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1407936"},{"key":"2026093006350980000_16.9.e121775.26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.4103\/2090-0686.192749","article-title":"Prevalence of dry eye disease in southern Egypt: a hospital-based outpatient clinic study","volume":"109","author":"Mostafa","year":"2016","journal-title":"J Egypt Ophthalmol Soc"},{"key":"2026093006350980000_16.9.e121775.27","first-page":"626","article-title":"Dry eye disease and depression-anxiety-stress: A hospital-based case control study in Turkey","volume":"31","author":"Yilmaz","year":"2015","journal-title":"Pak J Med Sci"},{"key":"2026093006350980000_16.9.e121775.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2011.05.029"},{"key":"2026093006350980000_16.9.e121775.29","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2011.78"},{"key":"2026093006350980000_16.9.e121775.30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0272808","article-title":"Symptomatic dry eye disease and associated factors among postgraduate students in Ethiopia","volume":"17","author":"Zeleke","year":"2022","journal-title":"PLoS One"},{"key":"2026093006350980000_16.9.e121775.31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.4103\/ejos.ejos_29_20","article-title":"Prevalence of dry eye disease among healthy Egyptian population","volume":"113","author":"Aziz","year":"2020","journal-title":"J Egypt Ophthalmol Soc"},{"key":"2026093006350980000_16.9.e121775.32","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1046\/j.1442-9071.2003.00634.x","article-title":"Prevalence and associations of dry eye syndrome in an older population: the Blue Mountains Eye Study","volume":"31","author":"Chia","year":"2003","journal-title":"Clinical Exper Ophthalmol"},{"key":"2026093006350980000_16.9.e121775.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2026.01.010"},{"key":"2026093006350980000_16.9.e121775.34","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2476"},{"key":"2026093006350980000_16.9.e121775.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108115"},{"key":"2026093006350980000_16.9.e121775.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.04.001"},{"key":"2026093006350980000_16.9.e121775.37","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2415-8-10","article-title":"Prevalence of dry eye syndrome and diabetic retinopathy in type 2 diabetic patients","volume":"8","author":"Manaviat","year":"2008","journal-title":"BMC Ophthalmol"},{"key":"2026093006350980000_16.9.e121775.38","doi-asserted-by":"crossref","first-page":"109149","DOI":"10.1016\/j.jdiacomp.2025.109149","article-title":"Is there a link between dry eye disease and diabetes mellitus? A systematic review and meta-analysis","volume":"39","author":"Chen","year":"2025","journal-title":"J Diabetes Complications"},{"key":"2026093006350980000_16.9.e121775.39","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1517\/13543784.2013.838557","article-title":"Changing trends in the treatment of dry-eye disease","volume":"22","author":"Dogru","year":"2013","journal-title":"Expert Opin Investig Drugs"},{"key":"2026093006350980000_16.9.e121775.40","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.18240\/ijo.2025.10.05","article-title":"Predictive analysis of dry eye diagnosis and digital screen usage: a cross-sectional study","volume":"18","author":"Ghimire","year":"2025","journal-title":"Int J Ophthalmol"},{"key":"2026093006350980000_16.9.e121775.41","article-title":"The Association of Screen Time, Sleep Quality, and Dry Eye Among College Students in Saudi Arabia","volume":"15","author":"Albalawi","year":"2023","journal-title":"Cureus"},{"key":"2026093006350980000_16.9.e121775.42","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.4103\/IJO.IJO_2760_22","article-title":"Dry eye symptoms and digital eyestrain - Emerging epidemics among university students due to online curriculum amid the COVID-19 pandemic. A cross-sectional study","volume":"71","author":"Jakhar","year":"2023","journal-title":"Indian J Ophthalmol"},{"key":"2026093006350980000_16.9.e121775.43","doi-asserted-by":"crossref","first-page":"71","DOI":"10.18051\/JBiomedKes.2024.v7.71-81","article-title":"Pterigium berhubungan dengan Sindroma Mata Kering pada Pengemudi Ojek Online","volume":"7","author":"Kartadinata","year":"2024","journal-title":"J Biomedika dan Kesehat"},{"key":"2026093006350980000_16.9.e121775.44","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/ina.12322","article-title":"External eye symptoms in indoor environments","volume":"27","author":"Wolkoff","year":"2017","journal-title":"Indoor Air"},{"key":"2026093006350980000_16.9.e121775.45","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.10363"},{"key":"2026093006350980000_16.9.e121775.46","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000041019","article-title":"Association between potential factors and dry eye disease: A systematic review and meta-analysis","volume":"103","author":"Yang","year":"2024","journal-title":"Medicine (Baltimore)"},{"key":"2026093006350980000_16.9.e121775.47","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jtos.2021.05.005","article-title":"The relationship between alcohol consumption and dry eye","volume":"21","author":"Magno","year":"2021","journal-title":"Ocul Surf"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2026-121775","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:35:46Z","timestamp":1790775346000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2026-121775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,30]]},"published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1136\/bmjopen-2026-121775"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2026-121775","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]}}}