{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T17:25:23Z","timestamp":1786296323162,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,1,27]],"date-time":"2019-01-27T00:00:00Z","timestamp":1548547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010318","name":"Landelijke Stichting voor Blinden en Slechtzienden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010318","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010372","name":"Rotterdamse Stichting Blindenbelangen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010372","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Primary vitreoretinal lymphoma [(P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content>]) is a rare malignancy of the eye localized in the retina, vitreous or choroid. Here, we aim to determine the value of the combination of innovative diagnostic methods for accurate differentiation between (P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content> and non\u2010(P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content> in patients with suspect uveitis or vitritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Multicolour flow cytometric immunophenotyping of cells in the vitreous samples was performed using the EuroFlow small sample tube. Additionally, cytokines\/chemokines and growth factors were measured in the vitreous specimens using a multiplex immunoassay. Data were evaluated in predefined clinical subgroups using <jats:sc>omniviz<\/jats:sc> unsupervised Pearson's correlation visualization and unsupervised heatmap analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 53 patients were prospectively included in the period 2012\u20132015. In the (P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content> subgroup (<jats:italic>n<\/jats:italic>\u00a0=\u00a010), nine cases showed aberrant surface membrane immunoglobulin (SmIg) light chain expression. In the non\u2010(P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content> group (<jats:italic>n<\/jats:italic>\u00a0=\u00a043) clearly skewed SmIg light chain expression was observed in two multiple sclerosis\u2010related uveitis cases, but not in other uveitis types. Soluble mediator measurement revealed high interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u201010\/<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 ratios, and high <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> levels in 9\/10 (P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content> cases, but not in any non\u2010(P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content> case. Further correlation and heatmap analysis revealed a minimal signature of cellular parameters (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19+ B cells, aberrant SmIg light chain expression) and cytokine parameters (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010\/<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 ratio &gt;1, high <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010, high <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101 <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>, high monocyte chemotactic protein\u20101, high macrophage inflammatory protein\u20101<jats:italic>\u03b2<\/jats:italic>) to reliably distinguish (P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content> from non\u2010(P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Here, we show the power of a combined cellular and proteomics strategy for detecting (P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content> in vitreous specimens, especially in cases with minor cellular (P)<jats:styled-content style=\"fixed-case\">VRL<\/jats:styled-content> infiltrates.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.14036","type":"journal-article","created":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T07:08:47Z","timestamp":1548659327000},"page":"626-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Combined cellular and soluble mediator analysis for improved diagnosis of vitreoretinal lymphoma"],"prefix":"10.1111","volume":"97","author":[{"given":"Joeri","family":"de Hoog","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem A.","family":"Dik","sequence":"additional","affiliation":[{"name":"Department of Immunology Laboratory Medical Immunology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim C.","family":"Heezen","sequence":"additional","affiliation":[{"name":"Department of Immunology Laboratory Medical Immunology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4610-4991","authenticated-orcid":false,"given":"Josianne C.","family":"ten Berge","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid M. 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