{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:22:56Z","timestamp":1782231776492,"version":"3.54.5"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:00:00Z","timestamp":1622592000000},"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:p><jats:bold>Purpose:<\/jats:bold> To investigate the risk of recurrent corneal erosion (RCE) in patients with atopic keratoconjunctivitis (AKC).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> This national, retrospective, matched cohort study enrolled 184,166 newly-diagnosed AKC patients, selected from the Taiwan National Health Insurance Research Database and identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 372.05. The control group comprised 184,166 non-AKC patients matched by age, sex, and potential comorbidities and they were selected from the Taiwan Longitudinal Health Insurance Database, 2000. Information from patients was gathered from 1 January 2004 to 31 December 2011, and both groups were traced from the index date until December 2013. The incidence and risk of RCE (ICD-9-CM code 361.42) was compared between the groups. The adjusted hazard ratio (HR) for RCE was obtained by a Cox proportional hazard regression analysis. The Kaplan\u2013Meier analysis was performed to calculate the cumulative incidence of RCE.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In total, 564 AKC patients and 406 non-AKC controls developed RCE during the follow-up span. The incidence of RCE was 1.45 times higher in AKC patients than in controls (95% confidence interval [CI] = 1.27\u20131.64; <jats:italic>P<\/jats:italic> &amp;lt; 0.0001). After adjusting for potential confounders, including diabetes mellitus, keratoconjunctivitis sicca, corneal transplantation, ocular blunt trauma, corneal dystrophy, and band keratopathy, AKC patients were 1.36 times more likely to develop RCE than controls (adjusted HR, 1.36; 95% CI = 1.19\u20131.54; <jats:italic>p<\/jats:italic> &amp;lt; 0.05).<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> AKC Patients had an increased risk of developing RCE and should be informed of this risk.<\/jats:p>","DOI":"10.3389\/fmed.2021.688355","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T05:58:51Z","timestamp":1622613531000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Association Between Atopic Keratoconjunctivitis and the Risk of Recurrent Corneal Erosion"],"prefix":"10.3389","volume":"8","author":[{"given":"Ren-Long","family":"Jan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Feng","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhi-Joung","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Huei","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuh-Shin","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1097\/ACI.0b013e32833e16e4","article-title":"Atopic keratoconjunctivitis and atopic dermatitis","volume":"10","author":"Guglielmetti","year":"2010","journal-title":"Curr Opin Allergy Clin Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.jaad.2013.10.036","article-title":"Atopic keratoconjunctivitis: a review","volume":"70","author":"Chen","year":"2014","journal-title":"J Am Acad Dermatol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/S0161-6420(98)94017-9","article-title":"Long-term follow-up of patients with atopic keratoconjunctivitis","volume":"105","author":"Power","year":"1998","journal-title":"Ophthalmology."},{"key":"B4","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/j.1398-9995.2004.00570.x","article-title":"Atopic keratoconjunctivitis","volume":"59","author":"Bonini","year":"2004","journal-title":"Allergy."},{"key":"B5","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.survophthal.2007.10.011","article-title":"Recurrent corneal erosion syndrome","volume":"53","author":"Das","year":"2008","journal-title":"Surv Ophthalmol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/sj.eye.6702005","article-title":"Pathogenesis, clinical features and management of recurrent corneal erosions","volume":"20","author":"Ramamurthi","year":"2006","journal-title":"Eye (Lond)."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e14964","DOI":"10.1097\/MD.0000000000014964","article-title":"Clinical course and risk factors of recurrent corneal erosion: observational study","volume":"98","author":"Nanba","year":"2019","journal-title":"Medicine."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1097\/ICO.0000000000002422","article-title":"Galectin-3, il-1a, il-6, and egf levels in corneal epithelium of patients with recurrent corneal erosion syndrome","volume":"39","author":"Candar","year":"2020","journal-title":"Cornea."},{"key":"B9","doi-asserted-by":"publisher","first-page":"325","DOI":"10.2147\/OPTH.S157430","article-title":"Recurrent corneal erosion: a comprehensive review","volume":"13","author":"Miller","year":"2019","journal-title":"Clin Ophthalmol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1016\/S0091-6749(99)70206-X","article-title":"Presence of eotaxin in tears of patients with atopic keratoconjunctivitis with severe corneal damage","volume":"103","author":"Fukagawa","year":"1999","journal-title":"J Allergy Clin Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/S0002-9394(02)01726-9","article-title":"Toxic eosinophil granule protein deposition in corneal ulcerations and scars associated with atopic keratoconjunctivitis","volume":"134","author":"Messmer","year":"2002","journal-title":"Am J Ophthalmol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"6390","DOI":"10.1167\/iovs.13-12547","article-title":"The corneal epithelial basement membrane: structure, function, and disease","volume":"54","author":"Torricelli","year":"2013","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s10384-007-0455-0","article-title":"Upregulation of matrix metalloproteinase in tear fluid of patients with recurrent corneal erosion","volume":"51","author":"Sakimoto","year":"2007","journal-title":"J J Ophthalmol."},{"key":"B14","first-page":"1266","article-title":"Matrix metalloproteinases in epithelia from human recurrent corneal erosion","volume":"40","author":"Garrana","year":"1999","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B15","first-page":"593","article-title":"Effects of eosinophil granule proteins on human corneal epithelial cell viability and morphology","volume":"38","author":"Trocme","year":"1997","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1111\/j.1398-9995.1995.tb01209.x","article-title":"Eosinophil cationic protein in tears of normal subjects and patients affected by vernal keratoconjunctivitis","volume":"50","author":"Leonardi","year":"1995","journal-title":"Allergy."},{"key":"B17","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1136\/bjo.80.6.556","article-title":"Eosinophil cationic protein in tears in allergic conjunctivitis","volume":"80","author":"Montan","year":"1996","journal-title":"Br J Ophthalmol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1097\/00003226-199111000-00011","article-title":"Detection by brush cytology of mast cells and eosinophils in allergic and vernal conjunctivitis","volume":"10","author":"Tsubota","year":"1991","journal-title":"Cornea."},{"key":"B19","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1097\/ACI.0000000000000571","article-title":"Pathogenesis and complications of chronic eye rubbing in ocular allergy","volume":"19","author":"Ben-Eli","year":"2019","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"5372","DOI":"10.1167\/iovs.16-19677","article-title":"Differential molecular expression of extracellular matrix and inflammatory genes at the corneal cone apex drives focal weakening in keratoconus","volume":"57","author":"Pahuja","year":"2016","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1007\/s10384-007-0461-2","article-title":"Concentration of soluble interleukin-6 receptors in tears of allergic conjunctival disease patients","volume":"51","author":"Shoji","year":"2007","journal-title":"Japn J Ophthalmol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1111\/cxo.12038","article-title":"Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus","volume":"96","author":"Balasubramanian","year":"2013","journal-title":"Clin Exp Optom."},{"key":"B23","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1097\/00003226-199907000-00011","article-title":"Differential effects of epidermal growth factor and interleukin 6 on corneal epithelial cells and vascular endothelial cells","volume":"18","author":"Nakamura","year":"1999","journal-title":"Cornea."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1001\/archopht.1992.01080210110036","article-title":"Interleukin 6 facilitates corneal epithelial wound closure in vivo","volume":"110","author":"Nishida","year":"1992","journal-title":"Arch Ophthalmol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1006\/exer.1993.1127","article-title":"Effects of egf, il-1 and their combination on in vitro corneal epithelial wound closure and cell chemotaxis","volume":"57","author":"Boisjoly","year":"1993","journal-title":"Exp Eye Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1097\/ICO.0b013e31815c18d6","article-title":"Elevated expression and activation of matrix metalloproteinase 8 in tear fluid in atopic blepharoconjunctivitis","volume":"27","author":"Maatta","year":"2008","journal-title":"Cornea."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1167\/iovs.02-0766","article-title":"Tear levels and activity of matrix metalloproteinase (mmp)-1 and mmp-9 in vernal keratoconjunctivitis","volume":"44","author":"Leonardi","year":"2003","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B28","first-page":"850","article-title":"Recurrent erosion","volume":"82","author":"Wood","year":"1984","journal-title":"Trans Am Ophthalmol Soc."},{"key":"B29","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1097\/00003226-200011000-00001","article-title":"Recurrent erosions of the cornea: epidemiology and treatment","volume":"19","author":"Reidy","year":"2000","journal-title":"Cornea."},{"key":"B30","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/eye.1994.89","article-title":"Recurrent corneal erosion: clinical features","volume":"8","author":"Hope-Ross","year":"1994","journal-title":"Eye (Lond)."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e035933","DOI":"10.1136\/bmjopen-2019-035933","article-title":"Risk of recurrent corneal erosion in patients with diabetes mellitus in taiwan: a population-based cohort study","volume":"10","author":"Jan","year":"2020","journal-title":"BMJ Open."},{"key":"B32","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1167\/iovs.61.3.21","article-title":"Corneal sensitivity and tear function in recurrent corneal erosion syndrome","volume":"61","author":"Kang","year":"2020","journal-title":"Invest OphthalmolVis Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"9580292","DOI":"10.1155\/2018\/9580292","article-title":"Total penetrating keratoplasty: indications, therapeutic approach, and long-term follow-up","volume":"2018","author":"Krysik","year":"2018","journal-title":"J Ophthalmol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.ajo.2006.04.033","article-title":"Decreased density of corneal basal epithelium and subbasal corneal nerve bundle changes in patients with diabetic retinopathy","volume":"142","author":"Chang","year":"2006","journal-title":"Am J Ophthalmol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.jtos.2017.08.003","article-title":"Tfos dews ii report executive summary","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul Surf."},{"key":"B36","doi-asserted-by":"publisher","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."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.688355\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T22:25:39Z","timestamp":1622759139000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.688355\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,2]]},"references-count":36,"alternative-id":["10.3389\/fmed.2021.688355"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.688355","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,2]]},"article-number":"688355"}}