Clinical Characteristics and Mixed Infection Patterns of Ocular Surface Infection with Epstein-Barr Virus

Clinical Characteristics and Mixed Infection Patterns of Ocular Surface Infection with Epstein-Barr Virus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Characteristics and Mixed Infection Patterns of Ocular Surface Infection with Epstein-Barr Virus Zihan SHEN, Yiyun LIU, Yilin LIU, Pei ZHANG, Yingyu LI, Zekai LI, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8349333/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Mar, 2026 Read the published version in Journal of Ophthalmic Inflammation and Infection → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose To analyze the clinical features of ocular surface diseases caused by Epstein-Barr virus (EBV) infection. Methods A retrospective case series study was conducted. Data from 48 patients (54 eyes) with EBV infection who visited Peking University Third Hospital between January 2023 and October 2025 were collected. Patient demographics and baseline information were recorded. Ophthalmic slit-lamp examination, ocular surface (conjunctiva/cornea) scrapings, bacterial culture of ocular secretions, real-time fluorescence quantitative PCR detection, EBV-specific antibody testing, and metagenomic next-generation sequencing (mNGS) were performed. Results Among patients infected with EBV on the ocular surface, the majority were middle-aged individuals in the 31–40 age group. The primary risk factors for onset were keeping pets (10/48), followed by colds (6/48); among those keeping pets, parrots were the most common (5/9). The main clinical manifestations were foreign body sensation (37/54) and yellow discharge (34/54). Common signs included mixed conjunctival hyperemia (31/54), follicles on the lower eyelid conjunctiva (17/54), papillae on the upper eyelid conjunctiva (8/54), and punctate epithelial defects on the cornea (17/54). In most ocular surface scrapings, small round lymphocytes were observed alongside a small number of reactive lymphocytes (44/54), which could simultaneously present with a large number of neutrophils (34/54). There was a significant difference between the presence of yellow discharge and the type of conjunctival hyperemia ( \(\:{\text{χ}}^{\text{2}}\text{=}\text{9.}\text{818,P}\text{=0.007}\) ). However, no statistically significant correlation was found between the presence of yellow discharge and the presence of neutrophils in the scraping results ( \(\:{\text{χ}}^{\text{2}}\text{=0.}\text{64,P}\text{>0.05}\) ). Significant differences were found in EBV viral loads among different groups of combined symptoms ( \(\:\text{F=4.}\text{207,P}\text{=0.02}\) ) and among different follicle groups ( \(\:\text{F=4.}\text{466,P}\text{=0.007}\) ). No statistically significant correlation was found between the lymphocyte count in the scraping and the EBV viral load in the affected eye ( \(\:\text{F=0.}\text{49,P}\text{>0.05}\) ). Conclusion EBV infection of the ocular surface is prone to concurrent infections; therefore, a detailed medical history inquiry is crucial. Ocular surface tissue scraping examination can rapidly and effectively aid in diagnosis. Epstein-Barr virus Ocular surface infection Ocular surface scrapings Co-infection Retrospective study Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 31 Mar, 2026 Read the published version in Journal of Ophthalmic Inflammation and Infection → Version 1 posted Editorial decision: Revision requested 23 Feb, 2026 Reviews received at journal 12 Feb, 2026 Reviewers agreed at journal 02 Feb, 2026 Reviews received at journal 02 Feb, 2026 Reviewers agreed at journal 02 Feb, 2026 Reviewers invited by journal 22 Dec, 2025 Editor assigned by journal 15 Dec, 2025 Submission checks completed at journal 15 Dec, 2025 First submitted to journal 12 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8349333","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":564161014,"identity":"b24fa54b-997a-4da3-92fd-20e49f961a4b","order_by":0,"name":"Zihan SHEN","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zihan","middleName":"","lastName":"SHEN","suffix":""},{"id":564161016,"identity":"48b60a33-6209-4500-b9bf-0c6469b7612c","order_by":1,"name":"Yiyun LIU","email":"","orcid":"","institution":"Peking University Third 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Virus","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-ophthalmic-inflammation-and-infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joii","sideBox":"Learn more about [Journal of Ophthalmic Inflammation and Infection](http://joii-journal.springeropen.com)","snPcode":"12348","submissionUrl":"https://submission.nature.com/new-submission/12348/3","title":"Journal of Ophthalmic Inflammation and Infection","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Epstein-Barr virus, Ocular surface infection, Ocular surface scrapings, Co-infection, Retrospective study","lastPublishedDoi":"10.21203/rs.3.rs-8349333/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8349333/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTo analyze the clinical features of ocular surface diseases caused by Epstein-Barr virus (EBV) infection.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA retrospective case series study was conducted. Data from 48 patients (54 eyes) with EBV infection who visited Peking University Third Hospital between January 2023 and October 2025 were collected. Patient demographics and baseline information were recorded. Ophthalmic slit-lamp examination, ocular surface (conjunctiva/cornea) scrapings, bacterial culture of ocular secretions, real-time fluorescence quantitative PCR detection, EBV-specific antibody testing, and metagenomic next-generation sequencing (mNGS) were performed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAmong patients infected with EBV on the ocular surface, the majority were middle-aged individuals in the 31\u0026ndash;40 age group. The primary risk factors for onset were keeping pets (10/48), followed by colds (6/48); among those keeping pets, parrots were the most common (5/9). The main clinical manifestations were foreign body sensation (37/54) and yellow discharge (34/54). Common signs included mixed conjunctival hyperemia (31/54), follicles on the lower eyelid conjunctiva (17/54), papillae on the upper eyelid conjunctiva (8/54), and punctate epithelial defects on the cornea (17/54). In most ocular surface scrapings, small round lymphocytes were observed alongside a small number of reactive lymphocytes (44/54), which could simultaneously present with a large number of neutrophils (34/54). There was a significant difference between the presence of yellow discharge and the type of conjunctival hyperemia (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\text{\u0026chi;}}^{\\text{2}}\\text{=}\\text{9.}\\text{818,P}\\text{=0.007}\\)\u003c/span\u003e\u003c/span\u003e). However, no statistically significant correlation was found between the presence of yellow discharge and the presence of neutrophils in the scraping results (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\text{\u0026chi;}}^{\\text{2}}\\text{=0.}\\text{64,P}\\text{\u0026gt;0.05}\\)\u003c/span\u003e\u003c/span\u003e). Significant differences were found in EBV viral loads among different groups of combined symptoms (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\text{F=4.}\\text{207,P}\\text{=0.02}\\)\u003c/span\u003e\u003c/span\u003e) and among different follicle groups (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\text{F=4.}\\text{466,P}\\text{=0.007}\\)\u003c/span\u003e\u003c/span\u003e). No statistically significant correlation was found between the lymphocyte count in the scraping and the EBV viral load in the affected eye (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\text{F=0.}\\text{49,P}\\text{\u0026gt;0.05}\\)\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eEBV infection of the ocular surface is prone to concurrent infections; therefore, a detailed medical history inquiry is crucial. Ocular surface tissue scraping examination can rapidly and effectively aid in diagnosis.\u003c/p\u003e","manuscriptTitle":"Clinical Characteristics and Mixed Infection Patterns of Ocular Surface Infection with Epstein-Barr Virus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-24 12:35:39","doi":"10.21203/rs.3.rs-8349333/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-23T12:21:48+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-12T06:49:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"212326703532236927018627094323654467720","date":"2026-02-02T11:53:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-02T10:52:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"55450345591990817917034977712750056891","date":"2026-02-02T09:12:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-22T13:32:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-15T10:42:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-15T10:39:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Ophthalmic Inflammation and Infection","date":"2025-12-12T23:20:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ophthalmic-inflammation-and-infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joii","sideBox":"Learn more about [Journal of Ophthalmic Inflammation and Infection](http://joii-journal.springeropen.com)","snPcode":"12348","submissionUrl":"https://submission.nature.com/new-submission/12348/3","title":"Journal of Ophthalmic Inflammation and Infection","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ac3f836b-8c33-446c-b327-0933756edb96","owner":[],"postedDate":"December 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T16:00:22+00:00","versionOfRecord":{"articleIdentity":"rs-8349333","link":"https://doi.org/10.1186/s12348-026-00579-w","journal":{"identity":"journal-of-ophthalmic-inflammation-and-infection","isVorOnly":false,"title":"Journal of Ophthalmic Inflammation and Infection"},"publishedOn":"2026-03-31 15:57:29","publishedOnDateReadable":"March 31st, 2026"},"versionCreatedAt":"2025-12-24 12:35:39","video":"","vorDoi":"10.1186/s12348-026-00579-w","vorDoiUrl":"https://doi.org/10.1186/s12348-026-00579-w","workflowStages":[]},"version":"v1","identity":"rs-8349333","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8349333","identity":"rs-8349333","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}