{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:02:31Z","timestamp":1791928951788,"version":"4.3.4"},"reference-count":40,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2026,7,27]]},"DOI":"10.1167\/iovs.67.8.55","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:30:37Z","timestamp":1785162637000},"page":"55","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Ocular Pharmacokinetics and Efficacy of Novel Tivozanib Eye Drops for Neovascular Age-Related Macular Degeneration"],"prefix":"10.1167","volume":"67","author":[{"given":"Kyosuke","family":"Satake","sequence":"first","affiliation":[{"name":"Research Division, Kyowa Kirin Co., Ltd. Sunto-gun, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Koshiba","sequence":"additional","affiliation":[{"name":"Research Division, Kyowa Kirin Co., Ltd. Sunto-gun, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Haniuda","sequence":"additional","affiliation":[{"name":"Manufacturing Division, Kyowa Kirin Co., Ltd. Sunto-gun, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Amano","sequence":"additional","affiliation":[{"name":"Research Division, Kyowa Kirin Co., Ltd. Sunto-gun, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Hiura","sequence":"additional","affiliation":[{"name":"Development Division, Kyowa Kirin Co., Ltd. Sunto-gun, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Ishii","sequence":"additional","affiliation":[{"name":"Research Division, Kyowa Kirin Co., Ltd. Sunto-gun, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Horita","sequence":"additional","affiliation":[{"name":"Development Division, Kyowa Kirin North America, Princeton, New Jersey, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"10386","key":"bib1","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1016\/S0140-6736(22)02609-5","article-title":"Age-related macular degeneration","volume":"401","author":"Guymer","year":"2023","journal-title":"Lancet"},{"issue":"2","key":"bib2","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1076\/opep.11.2.67.28158","article-title":"2002 Global update of available data on visual impairment: a compilation of population-based prevalence studies","volume":"11","author":"Pascolini","year":"2004","journal-title":"Ophthalmic Epidemiol"},{"issue":"15","key":"bib3","doi-asserted-by":"publisher","first-page":"3297","DOI":"10.3390\/jcm10153297","article-title":"Prevention of the onset of age-related macular degeneration","volume":"10","author":"Di Carlo","year":"2021","journal-title":"J Clin Med"},{"issue":"2","key":"bib4","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob Health"},{"issue":"1","key":"bib5","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S0002-9440(10)64525-7","article-title":"Overexpression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelium leads to the development of choroidal neovascularization","volume":"157","author":"Spilsbury","year":"2000","journal-title":"Am J Pathol"},{"issue":"9583","key":"bib6","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/S0140-6736(07)61104-0","article-title":"Clinical update: new treatments for age-related macular degeneration","volume":"370","author":"Wong","year":"2007","journal-title":"Lancet"},{"issue":"14","key":"bib7","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1056\/NEJMoa062655","article-title":"Ranibizumab versus verteporfin for neovascular age-related macular degeneration","volume":"355","author":"Brown","year":"2006","journal-title":"N Engl J Med"},{"issue":"14","key":"bib8","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1056\/NEJMoa054481","article-title":"Ranibizumab for neovascular age-related macular degeneration","volume":"355","author":"Rosenfeld","year":"2006","journal-title":"N Engl J Med"},{"issue":"20","key":"bib9","first-page":"1897","article-title":"Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results","volume":"364","author":"Martin","year":"2011","journal-title":"Ophthalmology"},{"issue":"7","key":"bib10","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.ophtha.2012.03.053","article-title":"Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results","volume":"119","author":"Martin","year":"2012","journal-title":"Ophthalmology"},{"issue":"12","key":"bib11","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1016\/j.ophtha.2012.09.006","article-title":"Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration","volume":"119","author":"Heier","year":"2012","journal-title":"Ophthalmology"},{"issue":"1","key":"bib12","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.ophtha.2019.04.017","article-title":"HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration","volume":"127","author":"Dugel","year":"2020","journal-title":"Ophthalmology"},{"issue":"3","key":"bib13","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.3390\/ijms22031170","article-title":"Neovascular macular degeneration: a review of etiology, risk factors, and recent advances in research and therapy","volume":"22","author":"Pugazhendhi","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"10326","key":"bib14","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/S0140-6736(22)00010-1","article-title":"Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials","volume":"399","author":"Heier","year":"2022","journal-title":"Lancet"},{"issue":"1","key":"bib15","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1517\/14728214.2014.884559","article-title":"Emerging treatments for wet age-related macular degeneration","volume":"19","author":"Smith","year":"2014","journal-title":"Expert Opin Emerg Drugs"},{"issue":"1","key":"bib16","doi-asserted-by":"publisher","first-page":"134","DOI":"10.3390\/pharmaceutics14010134","article-title":"Topical drug delivery to the posterior segment of the eye","volume":"14","author":"L\u00f6scher","year":"2022","journal-title":"Pharmaceutics"},{"issue":"10","key":"bib17","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1080\/17425247.2017.1272569","article-title":"How are we improving the delivery to back of the eye? Advances and challenges of novel therapeutic approaches","volume":"14","author":"Agrahari","year":"2017","journal-title":"Expert Opin Drug Deliv"},{"issue":"9","key":"bib18","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1097\/IAE.0000000000000179","article-title":"Clinical evaluation of pazopanib eye drops in healthy subjects and in subjects with neovascular age-related macular degeneration","volume":"34","author":"Singh","year":"2014","journal-title":"Retina"},{"issue":"3","key":"bib19","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.ophtha.2014.09.036","article-title":"Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration","volume":"122","author":"Csaky","year":"2015","journal-title":"Ophthalmology"},{"issue":"2","key":"bib20","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1111\/bcp.13794","article-title":"The developing regorafenib eye drops for neovascular age-related macular degeneration (DREAM) study: an open-label phase II trial","volume":"85","author":"Joussen","year":"2019","journal-title":"Br J Clin Pharmacol"},{"issue":"4","key":"bib21","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1021\/acs.jmedchem.7b01731","article-title":"The discovery of N-(1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6-((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide (Acrizanib), a VEGFR-2 inhibitor specifically designed for topical ocular delivery, as a therapy for neovascular age-related macular degeneration","volume":"61","author":"Adams","year":"2018","journal-title":"J Med Chem"},{"issue":"15","key":"bib22","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1080\/14656566.2019.1636031","article-title":"Innovative therapies for neovascular age-related macular degeneration","volume":"20","author":"Al-Khersan","year":"2019","journal-title":"Expert Opin Pharmacother"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.2147\/DDDT.S295223","article-title":"Vascular endothelial growth factor antagonists: promising players in the treatment of neovascular age-related macular degeneration","volume":"15","author":"Hussain","year":"2021","journal-title":"Drug Des Devel Ther"},{"issue":"14","key":"bib24","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1016\/j.addr.2005.09.004","article-title":"Topical and systemic drug delivery to the posterior segments","volume":"57","author":"Hughes","year":"2005","journal-title":"Adv Drug Deliv Rev"},{"issue":"6","key":"bib25","doi-asserted-by":"publisher","first-page":"e00545","DOI":"10.1002\/prp2.545","article-title":"Species differences in ocular pharmacokinetics and pharmacological activities of regorafenib and pazopanib eye-drops among rats, rabbits and monkeys","volume":"7","author":"Horita","year":"2019","journal-title":"Pharmacol Res Perspect"},{"issue":"18","key":"bib26","doi-asserted-by":"publisher","first-page":"9134","DOI":"10.1158\/0008-5472.CAN-05-4290","article-title":"KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affects functional vascular properties","volume":"66","author":"Nakamura","year":"2006","journal-title":"Cancer Res"},{"issue":"3","key":"bib27","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1158\/1078-0432.CCR-21-2334","article-title":"FDA Approval Summary: tivozanib for relapsed or refractory renal cell carcinoma","volume":"28","author":"Chang","year":"2022","journal-title":"Clin Cancer Res"},{"issue":"1","key":"bib30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejpb.2011.01.007","article-title":"State of the art of nanocrystals\u2013special features, production, nanotoxicology aspects and intracellular delivery","volume":"78","author":"M\u00fcller","year":"2011","journal-title":"Eur J Pharm Biopharm"},{"issue":"12","key":"bib32","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s11095-018-2519-x","article-title":"Topical drug delivery to the posterior segment of the eye: addressing the challenge of preclinical to clinical translation","volume":"35","author":"Rodrigues","year":"2018","journal-title":"Pharm Res"},{"issue":"3","key":"bib33","first-page":"264","article-title":"Determination of tear volume and tear flow","volume":"5","author":"Mishima","year":"1966","journal-title":"Invest Ophthalmol"},{"issue":"4","key":"bib34","first-page":"504","article-title":"Clinical pharmacokinetics of the eye. Proctor lecture","volume":"21","author":"Mishima","year":"1981","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s11912-007-0007-2","article-title":"Pazopanib: a novel multitargeted tyrosine kinase inhibitor","volume":"9","author":"Sonpavde","year":"2007","journal-title":"Curr Oncol Rep"},{"key":"bib36","first-page":"3","article-title":"Scientific viewpoints in ocular toxicity assessment: departure from conventional practice","volume":"32","author":"Onodera","year":"2013","journal-title":"Anim. Eye Res."},{"key":"bib37","first-page":"35","article-title":"Comparative study on ocular anatomical features among rabbits, beagle dogs and cynomolgus monkeys","volume":"32","author":"Atsumi","year":"2013","journal-title":"Anim. Eye Res."},{"issue":"1","key":"bib38","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.exer.2012.03.004","article-title":"Intraocular distribution of melanin in human, monkey, rabbit, minipig and dog eyes","volume":"98","author":"Durairaj","year":"2012","journal-title":"Exp Eye Res"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.addr.2017.12.008","article-title":"Implications of melanin binding in ocular drug delivery","volume":"126","author":"Rimpel\u00e4","year":"2018","journal-title":"Adv Drug Deliv Rev"},{"issue":"12","key":"bib40","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1167\/iovs.65.12.14","article-title":"Comprehensive pharmacokinetic evaluation of high melanin binder levofloxacin in rabbits shows potential of topical eye drops for posterior segment treatment","volume":"65","author":"Bahrpeyma","year":"2024","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib28","article-title":"EMA assessment report: Fotivda (tivozanib)","author":"European Medicines Agency"},{"key":"bib29","first-page":"641","article-title":"Eye irritation, in dermatotoxicology","author":"McDonald","year":"1987"},{"key":"bib31","volume-title":"FOTIVDA (tivozanib) capsules [package insert]","author":"AVEO Pharmaceuticals, Inc","year":"2021"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.8.55","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:22Z","timestamp":1791927142000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.8.55"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.67.8.55","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}