{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:45:50Z","timestamp":1782949550526,"version":"3.54.5"},"reference-count":40,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","ophthalmologyscience.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ophthalmology Science"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.xops.2026.101186","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:23:23Z","timestamp":1775197403000},"page":"101186","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and Biodistribution of Topical Laquinimod, an Immunomodulator Targeting Aryl Hydrocarbon Receptor: The LION Study"],"prefix":"10.1016","volume":"6","author":[{"given":"Dalia","family":"El Feky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Akhavanrezayat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azadeh","family":"Mobasserian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hareem","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2907-0050","authenticated-orcid":false,"given":"Osama","family":"Elaraby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9914-2935","authenticated-orcid":false,"given":"Negin","family":"Yavari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3208-7078","authenticated-orcid":false,"given":"Muhammad Sohail","family":"Halim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh Ngoc","family":"Tram Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0444-224X","authenticated-orcid":false,"given":"Anadi","family":"Khatri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunay Uludag","family":"Kirimli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6123-675X","authenticated-orcid":false,"given":"Ngoc Trong","family":"Tuong Than","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Vahtola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"T\u00f6rngren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Horung","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdy","family":"Moussa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1308-0583","authenticated-orcid":false,"given":"Charles","family":"DeBoer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prithvi","family":"Mruthyunjaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Or","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamdouh","family":"Kabeel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser","family":"Serag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana V.","family":"Do","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arto","family":"Urtti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6024-8441","authenticated-orcid":false,"given":"Quan Dong","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.xops.2026.101186_bib1","first-page":"11","article-title":"Regulation of the immune response by the aryl hydrocarbon receptor","volume":"49","author":"Guti\u00e9rrez-V\u00e1zquez","year":"2018","journal-title":"Immunity"},{"key":"10.1016\/j.xops.2026.101186_bib2","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.3389\/fimmu.2018.01713","article-title":"Aryl hydrocarbon receptor regulates apoptosis and inflammation in experimental autoimmune uveitis","volume":"9","author":"Huang","year":"2018","journal-title":"Front Immunol"},{"key":"10.1016\/j.xops.2026.101186_bib3","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3390\/ijms23010288","article-title":"Targeting AhR as a novel therapeutic modality against ocular inflammation","volume":"23","author":"Cannon","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.xops.2026.101186_bib4","doi-asserted-by":"crossref","first-page":"6777","DOI":"10.3390\/ijms21186777","article-title":"The aryl hydrocarbon receptor: a mediator and potential therapeutic target for ocular and non-ocular neurodegenerative diseases","volume":"21","author":"Choudhary","year":"2020","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.xops.2026.101186_bib5","doi-asserted-by":"crossref","first-page":"E6145","DOI":"10.1073\/pnas.1607843113","article-title":"Laquinimod arrests experimental autoimmune encephalomyelitis by activating the aryl hydrocarbon receptor","volume":"113","author":"Kaye","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.xops.2026.101186_bib6","series-title":"Topical ocular laquinimod in development for inflammatory eye disorders","author":"Garh\u00f6fer","year":"2023"},{"key":"10.1016\/j.xops.2026.101186_bib7","article-title":"Laquinimod effectively inhibits development of EAU and its associated immune effector responses","volume":"60","author":"Xu","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.xops.2026.101186_bib8","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.204.Supp.150.18","article-title":"Laquinimod arrests development of experimental autoimmune uveitis (EAU) and inhibits related immune processes, in the context of altered gut microbiota","volume":"204","author":"Xu","year":"2020","journal-title":"J Immunol"},{"key":"10.1016\/j.xops.2026.101186_bib9","article-title":"Laquinimod inhibits inflammation-induced angiogenesis in the cornea","volume":"7","author":"Li","year":"2020","journal-title":"Front Med (Lausanne)"},{"key":"10.1016\/j.xops.2026.101186_bib10","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1586\/ecp.12.12","article-title":"A once-daily oral drug in development for the treatment of relapsing-remitting multiple sclerosis","volume":"5","author":"Br\u00fcck","year":"2012","journal-title":"Expert Rev Clin Pharmacol"},{"key":"10.1016\/j.xops.2026.101186_bib11","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1177\/1756285613499424","article-title":"Efficacy and safety of laquinimod in multiple sclerosis: current status","volume":"6","author":"Haggiag","year":"2013","journal-title":"Ther Adv Neurol Disord"},{"key":"10.1016\/j.xops.2026.101186_bib12","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1056\/NEJMoa1104318","article-title":"Placebo-controlled trial of oral laquinimod for multiple sclerosis","volume":"366","author":"Comi","year":"2012","journal-title":"N Engl J Med"},{"key":"10.1016\/j.xops.2026.101186_bib13","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.2147\/DDDT.S55308","article-title":"Laquinimod in the treatment of multiple sclerosis: a review of the data so far","volume":"10","author":"Th\u00f6ne","year":"2016","journal-title":"Drug Des Devel Ther"},{"key":"10.1016\/j.xops.2026.101186_bib14","first-page":"87","article-title":"Impact of ocular complications on visual outcomes in adult patients with uveitis","volume":"30","author":"Barry","year":"2022","journal-title":"Ocul Immunol Inflamm"},{"key":"10.1016\/j.xops.2026.101186_bib15","series-title":"What is uveitis?","year":"2023"},{"key":"10.1016\/j.xops.2026.101186_bib16","series-title":"Preventable blindness: avoiding cumulative damage in uveitis","year":"2024"},{"key":"10.1016\/j.xops.2026.101186_bib17","first-page":"44","article-title":"Immunomodulatory therapy in non-infectious uveitis: current landscape, gaps, and future directions","volume":"31","author":"Rathinam","year":"2023","journal-title":"Ocul Immunol Inflamm"},{"key":"10.1016\/j.xops.2026.101186_bib18","doi-asserted-by":"crossref","first-page":"276","DOI":"10.18502\/jovr.v17i2.10804","article-title":"A review of systemic biologics and local immunosuppressive medications in uveitis","volume":"17","author":"Mehta","year":"2022","journal-title":"J Ophthalmic Vis Res"},{"key":"10.1016\/j.xops.2026.101186_bib19","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41433-023-02714-6","article-title":"Topical ciclosporin A for severe ocular surface inflammation: a real-world series of 1221 cases","volume":"38","author":"ElFadaly","year":"2024","journal-title":"Eye"},{"key":"10.1016\/j.xops.2026.101186_bib20","first-page":"18","article-title":"Current and emerging therapies for noninfectious uveitis: an update","volume":"15","author":"Miserocchi","year":"2025","journal-title":"J Ophthalmic Inflamm Infect"},{"key":"10.1016\/j.xops.2026.101186_bib21","first-page":"112","article-title":"A review of local therapy for the management of uveitic macular edema","volume":"10","author":"Taylor","year":"2021","journal-title":"Asia Pac J Ophthalmol (Phila)"},{"key":"10.1016\/j.xops.2026.101186_bib22","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1177\/1120672119885050","article-title":"Risk of intraocular pressure elevation after topical steroids in children and adults: a systematic review","volume":"30","author":"Musleh","year":"2020","journal-title":"Eur J Ophthalmol"},{"key":"10.1016\/j.xops.2026.101186_bib23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1167\/tvst.4.3.11","article-title":"Topical ocular drug delivery to the back of the eye by mucus-penetrating particles","volume":"4","author":"Schopf","year":"2015","journal-title":"Transl Vis Sci Technol"},{"key":"10.1016\/j.xops.2026.101186_bib24","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1208\/s12248-010-9183-3","article-title":"Ocular drug delivery","volume":"12","author":"Gaudana","year":"2010","journal-title":"AAPS J"},{"key":"10.1016\/j.xops.2026.101186_bib25","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejps.2018.03.034","article-title":"Corneal and conjunctival drug permeability: systematic comparison and pharmacokinetic impact in the eye","volume":"119","author":"Ramsay","year":"2018","journal-title":"Eur J Pharm Sci"},{"key":"10.1016\/j.xops.2026.101186_bib26","first-page":"1","article-title":"Nanocarrier-based ocular drug delivery: challenges and opportunities","volume":"19","author":"Al Yabhouni","year":"2024","journal-title":"Nanomedicine"},{"key":"10.1016\/j.xops.2026.101186_bib28","doi-asserted-by":"crossref","first-page":"819","DOI":"10.4155\/cli.12.66","article-title":"Laquinimod\u2014A promising oral drug for the treatment of relapsing-remitting multiple sclerosis","volume":"2","author":"Lee","year":"2012","journal-title":"Clin Invest"},{"key":"10.1016\/j.xops.2026.101186_bib29","first-page":"227","article-title":"Licaminlimab, a topical anti-TNF\u03b1 antibody fragment, in noninfectious anterior uveitis: results of a randomized phase II trial","volume":"237","author":"Dick","year":"2022","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.xops.2026.101186_bib30","series-title":"Tarsier pharma announces initiation of its phase 3 TRS4VISION trial of TRS01 in non-infectious anterior uveitis [Internet]. Tel Aviv (Israel): Tarsier Pharma","author":"Tarsier","year":"2024"},{"key":"10.1016\/j.xops.2026.101186_bib31","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/eye.2012.68","article-title":"Safety, tolerability, and bioavailability of topical SAR 1118, a novel antagonist of lymphocyte function-associated antigen-1: a phase 1b study","volume":"26","author":"Paskowitz","year":"2012","journal-title":"Eye (Lond)"},{"key":"10.1016\/j.xops.2026.101186_bib32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.survophthal.2009.07.005","article-title":"Nonsteroidal anti-inflammatory drugs in ophthalmology","volume":"55","author":"Kim","year":"2010","journal-title":"Surv Ophthalmol"},{"key":"10.1016\/j.xops.2026.101186_bib33","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/IAE.0b013e3181b094e6","article-title":"Vitreous nonsteroidal anti-inflammatory drug concentrations and prostaglandin E2 levels in vitrectomy patients treated with ketorolac 0.4%, bromfenac 0.09%, and nepafenac 0.1%","volume":"29","author":"Heier","year":"2009","journal-title":"Retina"},{"key":"10.1016\/j.xops.2026.101186_bib34","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1001\/jamaophthalmol.2013.5692","article-title":"Reduction of vitreous prostaglandin E2 levels after topical administration of ketorolac 0.45","volume":"132","author":"Schoenberger","year":"2014","journal-title":"JAMA Ophthalmol"},{"key":"10.1016\/j.xops.2026.101186_bib35","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.expneurol.2014.04.002","article-title":"Laquinimod, an up-and-coming immunomodulatory agent for treatment of multiple sclerosis","volume":"262","author":"Varrin-Doyer","year":"2014","journal-title":"Exp Neurol"},{"key":"10.1016\/j.xops.2026.101186_bib36","first-page":"P7","article-title":"Pharmacokinetics of laquinimod, an oral immunomodulatory agent in development for the treatment of relapsing-remitting multiple sclerosis","volume":"82","author":"Tumani","year":"2014","journal-title":"Neurology"},{"key":"10.1016\/j.xops.2026.101186_bib37","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jns.2011.02.019","article-title":"Insight into the mechanism of laquinimod action","volume":"306","author":"Br\u00fcck","year":"2011","journal-title":"J Neurol Sci"},{"key":"10.1016\/j.xops.2026.101186_bib38","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1021\/acs.molpharmaceut.5b00729","article-title":"Prediction of ocular drug distribution from systemic blood circulation","volume":"13","author":"Vellonen","year":"2016","journal-title":"Mol Pharm"},{"key":"10.1016\/j.xops.2026.101186_bib39","article-title":"Author correction: statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous","volume":"11","author":"Mysore","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.xops.2026.101186_bib40","first-page":"588","article-title":"Ocular intracameral pharmacokinetics for a cocktail of timolol, betaxolol and atenolol in rabbits","volume":"17","author":"Fayyaz","year":"2020","journal-title":"Mol Pharmaceut"},{"key":"10.1016\/j.xops.2026.101186_bib41","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.preteyeres.2016.12.001","article-title":"Pharmacokinetic aspects of retinal drug delivery","volume":"57","author":"del Amo","year":"2017","journal-title":"Prog Retin Eye Res"}],"container-title":["Ophthalmology Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666914526001247?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666914526001247?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:33:53Z","timestamp":1782948833000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666914526001247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["S2666914526001247"],"URL":"https:\/\/doi.org\/10.1016\/j.xops.2026.101186","relation":{},"ISSN":["2666-9145"],"issn-type":[{"value":"2666-9145","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Safety and Biodistribution of Topical Laquinimod, an Immunomodulator Targeting Aryl Hydrocarbon Receptor: The LION Study","name":"articletitle","label":"Article Title"},{"value":"Ophthalmology Science","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xops.2026.101186","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier Inc. on behalf of American Academy of Ophthalmology, Inc.","name":"copyright","label":"Copyright"}],"article-number":"101186"}}