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Independently, AC enhancement predicted ON infiltration, a major risk factor for advanced retinoblastoma (RB), in a small RB patient cohort. We aimed to review the supposed imaging biomarker for ON infiltration in a large RB cohort and with respect to the recently described orbital GS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This IRB\u2013approved retrospective single-center study encompassed 539 orbital MRIs performed with an orbital coil and with the children under general anesthesia. Differences of signal intensity ratios (\u2206SIRs) of the AC to the lens were determined between non-contrast\u00a0and GBCA\u2013enhanced T1-weighted images and were correlated with histopathologic presence of ON infiltration.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>\u2206SIR of the RB eye was an independent, significant predictor for ON invasion in multivariate analysis with adjustment for tumor size (<jats:italic>p<\/jats:italic> &lt; 0.05) and increased with infiltration level.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>GBCA enhancement of the AC predicts ON infiltration. This might be caused by impairment of the orbital glymphatic system, which is supposed to clear toxic metabolites from the retina to the postlaminar ON. In RB with ON infiltration, this efflux path is likely to be inhibited, which is supposed to result in disturbed retinal homeostasis, release of vascular endothelial growth factor, and iris neovascularization, which increases penetration of GBCA into the AC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Key Points<\/jats:title>\n                <jats:p>\u2022 <jats:italic>Infiltration of the optic nerve can be predicted by anterior chamber enhancement after intravenous MRI contrast agent administration.<\/jats:italic><\/jats:p>\n                <jats:p>\u2022 <jats:italic>Increased anterior chamber enhancement in retinoblastoma with optic nerve infiltration might result from dysfunction of the orbital glymphatic system with disturbance of retinal homeostasis and consecutive iris neovascularization.<\/jats:italic><\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00330-022-08778-4","type":"journal-article","created":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T05:02:35Z","timestamp":1651899755000},"page":"7354-7364","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Anterior chamber enhancement predicts optic nerve infiltration in retinoblastoma"],"prefix":"10.1007","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-0428","authenticated-orcid":false,"given":"Katerina","family":"Deike-Hofmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"von Lampe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maija","family":"Eerikaeinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Ting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Schl\u00fcter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz-Peter","family":"Schlemmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos E.","family":"Bechrakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Forsting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Radbruch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,7]]},"reference":[{"issue":"3","key":"8778_CR1","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1002\/1097-0142(19940201)73:3<692::AID-CNCR2820730331>3.0.CO;2-8","volume":"73","author":"C Shields","year":"1993","unstructured":"Shields C, Shields JA, Baez K, Cater IR, De P (1993) Optic nerve invasion of retinoblastoma metastatic potential and clinical risk factors. 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Deike-Hofmann: lecture payment by GE, financial study support: Bayer AG, Guerbet; A. Radbruch: personal fees for consulting and talks (within the last 3 years): Bayer, Guerbet, Novartis; financial study support: Bayer, Guerbet.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"No complex statistical methods were necessary for this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statistics and biometry"}},{"value":"Written informed consent was waived by the Institutional Review Board.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Institutional review board approval was obtained.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Some study subjects or cohorts have been previously reported in Deike-Hofmann et al, The anterior eye chamber: entry of the natural excretion pathway of gadolinium contrast agents? Eur Radiol, 2020.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Study subjects or cohorts overlap"}},{"value":"\u2022 retrospective\u2022 diagnostic or prognostic study\u2022 performed at one institution","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Methodology"}}]}}