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It is classified as primary (PVR-LBCL) or secondary (SVR-LBCL) based on the initial site of manifestation. Owing to limited prospective data and absent standardized guidelines, treatment remains challenging. This dual-center retrospective study aimed to evaluate outcomes of methotrexate (MTX) intravitreal (itv.), Rituximab itv., or combinatorial itv. therapy (R-MTX) and assess the impact of additional systemic immunochemotherapy. Among 65 patients (median age 72 years) included, 55.4% (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200936) had PVR-LBCL. The median time to diagnosis was 31 days (1\u20132805). Over a median follow-up of 23.2 months, 35 patients relapsed. MTX itv. showed a trend toward better ocular relapse-free-survival than Rituximab itv. (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.07). Intriguingly, patients receiving R-MTX itv. experienced no relapses throughout follow-up. In general, addition of systemic therapy was associated with significantly longer relapse-free-survival compared to itv. monotherapy (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.05). Keratopathy and elevated intraocular pressure were common side effects with MTX itv. and Rituximab itv., respectively. Despite compelling findings and being one of the largest cohorts published to date, the heterogeneity of the patient population and small subgroups limit direct clinical translation. Nonetheless, this study provides a strong foundation for the design of future clinical trials.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-37804-4","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T10:06:35Z","timestamp":1771063595000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Real world outcomes of intravitreal and systemic therapy in primary and secondary vitreoretinal lymphoma"],"prefix":"10.1038","volume":"16","author":[{"given":"Sina A.","family":"Beer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Huber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Nasyrov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse","family":"Wolfram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Pietzsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen","family":"Schenk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wedrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Lengerke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deshka","family":"Doycheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Deuter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"S\u00fcsskind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Wirths","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Merle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"37804_CR1","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1182\/blood.2020008235","volume":"138","author":"C Soussain","year":"2021","unstructured":"Soussain, C., Malaise, D. & Cassoux, N. 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The Funding section now reads: \u201cOpen Access funding enabled and organized by Projekt DEAL. We acknowledge support from the Open Access Publication Fund of the University of T\u00fcbingen.\u201d The original Article has been corrected.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This retrospective study did not require patient consent and was conducted in accordance with the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}],"article-number":"6513"}}