{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:37:24Z","timestamp":1791005844058,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>BRAF and MEK inhibitors targeting the RAS\/MAPK pathway are increasingly used in pediatric oncology, particularly for gliomas and neurofibromatosis type 1\u2013associated plexiform neurofibromas (PN). While ocular adverse events (OAE), such as uveitis and MEK inhibitor\u2010associated retinopathy (MEKAR), are well documented in adults, pediatric data remain limited,\u00a0as are data\u00a0regarding\u00a0the effect on\u00a0visual acuity (VA) in optic pathway gliomas (OPG) and\u00a0orbital plexiform neurofibromas (OPN).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study reviewed pediatric patients treated with BRAF and\/or MEK inhibitors (years\u00a02015\u20132024). Ophthalmologic assessments, including VA and optical coherence tomography (OCT), were conducted at baseline and follow\u2010up. Patients were categorized based on optic pathway involvement (OPG\/OPN vs. non\u2010OPG\/OPN).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 62 patients (120 eyes), OAE occurred in 3 (4.8%): 1\/29 in the OPG\/OPN group and 2\/33 in the non\u2010OPG\/OPN group. All were reversible with dose adjustment or discontinuation. In the OPG\/OPN group, VA data were available for 35 eyes, with stability in 74% (26\/35), improvement in 17% (6\/35), and a decline in 9% (3\/35). In the non\u2010OPG\/OPN group (57 eyes), VA remained stable in 91% (52\/57). Optic disc appearance, retinal nerve fiber layer thickness, and macular thickness remained stable over a 22\u2010month median follow\u2010up\u00a0in both groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BRAF and MEK inhibitors demonstrate ocular safety in children, including those with OPG\/OPN, with rare, reversible OAE and stable VA. These findings support their use in\u00a0pediatric\u00a0patients\u00a0even\u00a0with optic pathway involvement. Regular ophthalmologic monitoring with OCT and VA assessments remains essential for safe, long\u2010term use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.31709","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:31:07Z","timestamp":1744158667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ocular Safety and Visual Acuity Stability in Pediatric Patients With Optic Pathway Gliomas and Orbital Plexiform Neurofibromas Treated With BRAF and MEK Inhibitors"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6694-1573","authenticated-orcid":false,"given":"Aviv","family":"Sever","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology Schneider Children's Medical Center  Petah Tikva Israel"},{"name":"Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gad","family":"Dotan","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"Schneider Children's Medical Center Ophthalmology Unit  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafna","family":"Brik","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology Schneider Children's Medical Center  Petah Tikva Israel"},{"name":"Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariela","family":"Zaikin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Schneider Children's Medical Center  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Toledano","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology Schneider Children's Medical Center  Petah Tikva Israel"},{"name":"Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201020\u20100916"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520\u2010024\u201008810\u2010x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(12)60868\u2010X"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2014.07.003"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(12)70270\u2010X"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.05.038"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab047"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA2303815\/SUPPL_FILE\/NEJMOA2303815_DATA\u2010SHARING.PDF"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2016.09.020"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3171\/FOC\u201007\/11\/E2"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol31050199"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27600"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523\u2010022\u201000888\u20109"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaapos.2016.01.012"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nop\/npae038"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/AOS.14659"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000002451"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00417\u2010018\u20104007\u20108"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(19)30277\u20103"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381\u2010021\u201005127\u20106"}],"container-title":["Pediatric Blood &amp; 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