{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T13:26:40Z","timestamp":1775136400634,"version":"3.50.1"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ophthalmol Ther"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1007\/s40123-026-01358-5","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T07:59:18Z","timestamp":1773388758000},"page":"1195-1204","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ocular Half-Life: What it Does and Does Not Mean for Intravitreal Anti-angiogenic Drug Durability"],"prefix":"10.1007","volume":"15","author":[{"given":"Robert","family":"Avery","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheikh","family":"Diack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Holekamp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustapha","family":"Lhor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florie","family":"Mar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0493-2863","authenticated-orcid":false,"given":"Katie","family":"Maass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"issue":"12","key":"1358_CR1","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1038\/s41433-022-02149-5","volume":"36","author":"R Gale","year":"2022","unstructured":"Gale R, Cox O, Keenan C, Chakravarthy U. Health technology assessment of new retinal treatments; the need to capture healthcare capacity issues. Eye (Lond). 2022;36(12):2236\u20138. https:\/\/doi.org\/10.1038\/s41433-022-02149-5.","journal-title":"Eye (Lond)"},{"key":"1358_CR2","doi-asserted-by":"publisher","first-page":"905","DOI":"10.2147\/JEP.S259298","volume":"13","author":"SM Kaiser","year":"2021","unstructured":"Kaiser SM, Arepalli S, Ehlers JP. Current and future anti-VEGF agents for neovascular age-related macular degeneration. J Exp Pharmacol. 2021;13:905\u201312. https:\/\/doi.org\/10.2147\/JEP.S259298.","journal-title":"J Exp Pharmacol"},{"issue":"10","key":"1358_CR3","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1080\/17425255.2024.2401600","volume":"20","author":"MW Stewart","year":"2024","unstructured":"Stewart MW. Intraocular drugs: pharmacokinetic strategies and the influence on efficacy and durability. Expert Opin Drug Metab Toxicol. 2024;20(10):977\u201387. https:\/\/doi.org\/10.1080\/17425255.2024.2401600.","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"1358_CR4","volume-title":"Physiology, zero and first order kinetics. StatPearls","author":"CS Borowy","year":"2025","unstructured":"Borowy CS, Ashurst JV. Physiology, zero and first order kinetics. StatPearls. Treasure Island: StatPearls Publishing; 2025."},{"key":"1358_CR5","volume-title":"Elimination half-life of drugs. StatPearls","author":"J Hallare","year":"2025","unstructured":"Hallare J, Gerriets V. Elimination half-life of drugs. StatPearls. Treasure Island: StatPearls Publishing; 2025."},{"issue":"11","key":"1358_CR6","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.13.11.14","volume":"13","author":"C Diack","year":"2024","unstructured":"Diack C, Gibiansky L, Jaminion F, et al. Ocular pharmacokinetics of faricimab following intravitreal administration in patients with retinal disease. Transl Vis Sci Technol. 2024;13(11):14. https:\/\/doi.org\/10.1167\/tvst.13.11.14.","journal-title":"Transl Vis Sci Technol"},{"issue":"9","key":"1358_CR7","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.1021\/acs.molpharmaceut.5b00849","volume":"13","author":"LA Hutton-Smith","year":"2016","unstructured":"Hutton-Smith LA, Gaffney EA, Byrne HM, Maini PK, Schwab D, Mazer NA. A mechanistic model of the intravitreal pharmacokinetics of large molecules and the pharmacodynamic suppression of ocular vascular endothelial growth factor levels by ranibizumab in patients with neovascular age-related macular degeneration. Mol Pharm. 2016;13(9):2941\u201350. https:\/\/doi.org\/10.1021\/acs.molpharmaceut.5b00849.","journal-title":"Mol Pharm"},{"issue":"11","key":"1358_CR8","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.15252\/emmm.201505889","volume":"8","author":"JT Regula","year":"2016","unstructured":"Regula JT, von Leithner PL, Foxton R, et al. Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. EMBO Mol Med. 2016;8(11):1265\u201388. https:\/\/doi.org\/10.15252\/emmm.201505889.","journal-title":"EMBO Mol Med"},{"issue":"4","key":"1358_CR9","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/s41433-019-0583-z","volume":"34","author":"A Sharma","year":"2020","unstructured":"Sharma A, Kumar N, Kuppermann BD, Bandello F. Brolucizimab-leading an era of structural revolution for long-term VEGF suppression. Eye (Lond). 2020;34(4):611\u20133. https:\/\/doi.org\/10.1038\/s41433-019-0583-z.","journal-title":"Eye (Lond)"},{"issue":"6","key":"1358_CR10","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.8.6.1","volume":"8","author":"SR Crowell","year":"2019","unstructured":"Crowell SR, Wang K, Famili A, et al. Influence of charge, hydrophobicity, and size on vitreous pharmacokinetics of large molecules. Transl Vis Sci Technol. 2019;8(6):1. https:\/\/doi.org\/10.1167\/tvst.8.6.1.","journal-title":"Transl Vis Sci Technol"},{"issue":"2","key":"1358_CR11","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1021\/acs.molpharmaceut.9b01191","volume":"17","author":"A Caruso","year":"2020","unstructured":"Caruso A, F\u00fcth M, Alvarez-Sanchez R, et al. Ocular half-life of intravitreal biologics in humans and other species: meta-analysis and model-based prediction. Mol Pharm. 2020;17(2):695\u2013709. https:\/\/doi.org\/10.1021\/acs.molpharmaceut.9b01191.","journal-title":"Mol Pharm"},{"issue":"6","key":"1358_CR12","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.1021\/acs.molpharmaceut.0c01218","volume":"18","author":"P Jakubiak","year":"2021","unstructured":"Jakubiak P, Alvarez-Sanchez R, Fueth M, et al. Ocular pharmacokinetics of intravitreally injected protein therapeutics: comparison among standard-of-care formats. Mol Pharm. 2021;18(6):2208\u201317. https:\/\/doi.org\/10.1021\/acs.molpharmaceut.0c01218.","journal-title":"Mol Pharm"},{"issue":"12","key":"1358_CR13","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.65.12.21","volume":"65","author":"P Lamirande","year":"2024","unstructured":"Lamirande P, Gaffney EA, Gertz M, Maini PK, Crawshaw JR, Caruso A. A first-passage model of intravitreal drug delivery and residence time-influence of ocular geometry, individual variability, and injection location. Invest Ophthalmol Vis Sci. 2024;65(12):21. https:\/\/doi.org\/10.1167\/iovs.65.12.21.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"2","key":"1358_CR14","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1080\/02713683.2022.2033271","volume":"48","author":"RH Luo","year":"2023","unstructured":"Luo RH, Tram NK, Parekh AM, Puri R, Reilly MA, Swindle-Reilly KE. The roles of vitreous biomechanics in ocular disease, biomolecule transport, and pharmacokinetics. Curr Eye Res. 2023;48(2):195\u2013207. https:\/\/doi.org\/10.1080\/02713683.2022.2033271.","journal-title":"Curr Eye Res"},{"issue":"12","key":"1358_CR15","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1080\/17425255.2017.1404987","volume":"13","author":"M Edington","year":"2017","unstructured":"Edington M, Connolly J, Chong NV. Pharmacokinetics of intravitreal anti-VEGF drugs in vitrectomized versus non-vitrectomized eyes. Expert Opin Drug Metab Toxicol. 2017;13(12):1217\u201324. https:\/\/doi.org\/10.1080\/17425255.2017.1404987.","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"1","key":"1358_CR16","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1021\/acschemneuro.7b00185","volume":"9","author":"PJ Tonge","year":"2018","unstructured":"Tonge PJ. Drug-target kinetics in drug discovery. ACS Chem Neurosci. 2018;9(1):29\u201339. https:\/\/doi.org\/10.1021\/acschemneuro.7b00185.","journal-title":"ACS Chem Neurosci"},{"issue":"10","key":"1358_CR17","doi-asserted-by":"publisher","first-page":"3421","DOI":"10.1021\/mp500160v","volume":"11","author":"J Yang","year":"2014","unstructured":"Yang J, Wang X, Fuh G, et al. Comparison of binding characteristics and in vitro activities of three inhibitors of vascular endothelial growth factor A. Mol Pharm. 2014;11(10):3421\u201330. https:\/\/doi.org\/10.1021\/mp500160v.","journal-title":"Mol Pharm"},{"issue":"11","key":"1358_CR18","doi-asserted-by":"publisher","first-page":"6027","DOI":"10.1021\/acs.analchem.4c06023","volume":"97","author":"JG Quinn","year":"2025","unstructured":"Quinn JG. Solution-phase kinetics of ranibizumab binding VEGF using solid-phase surface plasmon resonance. Anal Chem. 2025;97(11):6027\u201333. https:\/\/doi.org\/10.1021\/acs.analchem.4c06023.","journal-title":"Anal Chem"},{"issue":"7","key":"1358_CR19","first-page":"1501","volume":"56","author":"J Tietz","year":"2015","unstructured":"Tietz J, Spohn G, Schmid G, et al. Affinity and potency of RTH258 (ESBA1008), a novel inhibitor of vascular endothelial growth factor a for the treatment of retinal disorders. Invest Ophthalmol Vis Sci. 2015;56(7):1501.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"11","key":"1358_CR20","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.13.11.13","volume":"13","author":"C Diack","year":"2024","unstructured":"Diack C, Avery RL, Cheung CMG, et al. Ocular pharmacodynamics of intravitreal faricimab in patients with neovascular age-related macular degeneration or diabetic macular edema. Transl Vis Sci Technol. 2024;13(11):13. https:\/\/doi.org\/10.1167\/tvst.13.11.13.","journal-title":"Transl Vis Sci Technol"},{"issue":"11","key":"1358_CR21","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1136\/bjophthalmol-2015-308264","volume":"100","author":"S Fauser","year":"2016","unstructured":"Fauser S, Muether PS. Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times. Br J Ophthalmol. 2016;100(11):1494\u20138. https:\/\/doi.org\/10.1136\/bjophthalmol-2015-308264.","journal-title":"Br J Ophthalmol"},{"issue":"3","key":"1358_CR22","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.ajo.2014.05.025","volume":"158","author":"S Fauser","year":"2014","unstructured":"Fauser S, Schwabecker V, Muether PS. Suppression of intraocular vascular endothelial growth factor during aflibercept treatment of age-related macular degeneration. Am J Ophthalmol. 2014;158(3):532\u20136. https:\/\/doi.org\/10.1016\/j.ajo.2014.05.025.","journal-title":"Am J Ophthalmol"},{"issue":"10","key":"1358_CR23","doi-asserted-by":"publisher","first-page":"2082","DOI":"10.1016\/j.ophtha.2012.07.041","volume":"119","author":"PS Muether","year":"2012","unstructured":"Muether PS, Hermann MM, Viebahn U, Kirchhof B, Fauser S. Vascular endothelial growth factor in patients with exudative age-related macular degeneration treated with ranibizumab. Ophthalmology. 2012;119(10):2082\u20136. https:\/\/doi.org\/10.1016\/j.ophtha.2012.07.041.","journal-title":"Ophthalmology"},{"issue":"16","key":"1358_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241613004","volume":"24","author":"BH Moon","year":"2023","unstructured":"Moon BH, Kim Y, Kim SY. Twenty years of anti-vascular endothelial growth factor therapeutics in neovascular age-related macular degeneration treatment. Int J Mol Sci. 2023;24(16):13004. https:\/\/doi.org\/10.3390\/ijms241613004.","journal-title":"Int J Mol Sci"},{"key":"1358_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.109162","volume":"222","author":"M Lamminsalo","year":"2022","unstructured":"Lamminsalo M, Urtti A, Ranta VP. Quantitative pharmacokinetic analyses of anterior and posterior elimination routes of intravitreal anti-VEGF macromolecules using published human and rabbit data. Exp Eye Res. 2022;222:109162. https:\/\/doi.org\/10.1016\/j.exer.2022.109162.","journal-title":"Exp Eye Res"},{"issue":"5","key":"1358_CR26","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1007\/s00417-024-06695-4","volume":"263","author":"V Chaudhary","year":"2025","unstructured":"Chaudhary V, Mar F, Amador MJ, et al. Emerging clinical evidence of a dual role for Ang-2 and VEGF-A blockade with faricimab in retinal diseases. Graefes Arch Clin Exp Ophthalmol. 2025;263(5):1239\u201347. https:\/\/doi.org\/10.1007\/s00417-024-06695-4.","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"issue":"11","key":"1358_CR27","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1016\/j.ophtha.2014.05.009","volume":"121","author":"AC Ho","year":"2014","unstructured":"Ho AC, Busbee BG, Regillo CD, et al. Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2014;121(11):2181\u201392. https:\/\/doi.org\/10.1016\/j.ophtha.2014.05.009.","journal-title":"Ophthalmology"},{"issue":"8","key":"1358_CR28","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.oret.2020.11.004","volume":"5","author":"AM Khanani","year":"2021","unstructured":"Khanani AM, Callanan D, Dreyer R, et al. End-of-study results for the Ladder phase 2 trial of the Port Delivery System with ranibizumab for neovascular age-related macular degeneration. Ophthalmol Retina. 2021;5(8):775\u201387. https:\/\/doi.org\/10.1016\/j.oret.2020.11.004.","journal-title":"Ophthalmol Retina"},{"issue":"1","key":"1358_CR29","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41433-021-01625-8","volume":"36","author":"SJ Talks","year":"2022","unstructured":"Talks SJ, Stratton I, Peto T, et al. Aflibercept in clinical practice; visual acuity, injection numbers and adherence to treatment, for diabetic macular oedema in 21 UK hospitals over 3 years. Eye (Lond). 2022;36(1):72\u20137. https:\/\/doi.org\/10.1038\/s41433-021-01625-8.","journal-title":"Eye (Lond)"},{"issue":"2","key":"1358_CR30","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1136\/bjophthalmol-2020-315933","volume":"105","author":"TA Ciulla","year":"2021","unstructured":"Ciulla TA, Pollack JS, Williams DF. Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular oedema: a real-world analysis of 28,658 patient eyes. Br J Ophthalmol. 2021;105(2):216\u201321. https:\/\/doi.org\/10.1136\/bjophthalmol-2020-315933.","journal-title":"Br J Ophthalmol"},{"key":"1358_CR31","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.2147\/OPTH.S409103","volume":"17","author":"G Reitan","year":"2023","unstructured":"Reitan G, Kjellevold Haugen IB, Andersen K, Bragadottir R, Bindesboll C. Through the eyes of patients: understanding treatment burden of intravitreal anti-VEGF injections for nAMD patients in Norway. Clin Ophthalmol. 2023;17:1465\u201374. https:\/\/doi.org\/10.2147\/OPTH.S409103.","journal-title":"Clin Ophthalmol"},{"issue":"1","key":"1358_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.xops.2025.100947","volume":"6","author":"MS Steinkerchner","year":"2026","unstructured":"Steinkerchner MS, Lee LH, Manda AR, et al. Classification of diabetic retinopathy severity with aqueous VEGF levels: a prospective, observational study. Ophthalmol Sci. 2026;6(1):100947. https:\/\/doi.org\/10.1016\/j.xops.2025.100947.","journal-title":"Ophthalmol Sci"},{"key":"1358_CR33","unstructured":"Stewart MW. PopPK modeling and simulation of ocular clearance for aflibercept 8 mg vs. 2 mg and associated durability of effect (abstract). Presented at the American Academy of Ophthalmology Meeting. Chicago, IL, October 18\u201321, 2024."},{"issue":"11","key":"1358_CR34","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1038\/eye.2016.149","volume":"30","author":"G Liew","year":"2016","unstructured":"Liew G, Lee AY, Zarranz-Ventura J, et al. The UK neovascular AMD database report 3: inter-centre variation in visual acuity outcomes and establishing real-world measures of care. Eye (Lond). 2016;30(11):1462\u20138. https:\/\/doi.org\/10.1038\/eye.2016.149.","journal-title":"Eye (Lond)"},{"issue":"10","key":"1358_CR35","doi-asserted-by":"publisher","first-page":"3185","DOI":"10.1007\/s00417-022-05679-6","volume":"260","author":"M Nicolo","year":"2022","unstructured":"Nicolo M, Ciucci F, Nardi M, et al. PERSEUS-IT 24-month analysis: a prospective observational study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in Italy in patients with neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2022;260(10):3185\u201395. https:\/\/doi.org\/10.1007\/s00417-022-05679-6.","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"issue":"8","key":"1358_CR36","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081869","volume":"9","author":"M Khan","year":"2020","unstructured":"Khan M, Aziz AA, Shafi NA, Abbas T, Khanani AM. Targeting angiopoietin in retinal vascular diseases: a literature review and summary of clinical trials involving faricimab. Cells. 2020;9(8):1869. https:\/\/doi.org\/10.3390\/cells9081869.","journal-title":"Cells"},{"key":"1358_CR37","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5016916","volume":"2020","author":"RL Gurung","year":"2020","unstructured":"Gurung RL, FitzGerald LM, McComish BJ, Verma N, Burdon KP. Identifying genetic risk factors for diabetic macular edema and the response to treatment. J Diabetes Res. 2020;2020:5016916. https:\/\/doi.org\/10.1155\/2020\/5016916.","journal-title":"J Diabetes Res"},{"key":"1358_CR38","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1875860","volume":"2020","author":"WM Wong","year":"2020","unstructured":"Wong WM, Chee C, Bhargava M, et al. Systemic factors associated with treatment response in diabetic macular edema. J Ophthalmol. 2020;2020:1875860. https:\/\/doi.org\/10.1155\/2020\/1875860.","journal-title":"J Ophthalmol"},{"issue":"7","key":"1358_CR39","first-page":"3154","volume":"65","author":"PK Kaiser","year":"2024","unstructured":"Kaiser PK, Turner KC, Bihorel S, et al. Population pharmacokinetic modeling and simulation of ocular clearance for aflibercept 8 mg and 2 mg and association with durability of effect. Invest Ophthalmol Vis Sci. 2024;65(7):3154.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1358_CR40","unstructured":"US Food and Drug Administration: EYLEA\u00ae (aflibercept) injection, for intravitreal use. Prescribing Information. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/125387s087lbl.pdf. Accessed Oct 2025."},{"key":"1358_CR41","unstructured":"Office of Clinical Pharmacology Review: EYLEA\u00ae HD (aflibercept). https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2024\/761355Orig1s000ClinPharmR.pdf. Accessed Oct 2025."},{"issue":"4","key":"1358_CR42","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1097\/IAE.0000000000002566","volume":"40","author":"DV Do","year":"2020","unstructured":"Do DV, Rhoades W, Nguyen QD. Pharmacokinetic study of intravitreal aflibercept in humans with neovascular age-related macular degeneration. Retina. 2020;40(4):643\u20137. https:\/\/doi.org\/10.1097\/IAE.0000000000002566.","journal-title":"Retina"},{"issue":"4","key":"1358_CR43","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000002710","volume":"40","author":"A Caruso","year":"2020","unstructured":"Caruso A, Mazer NA. Correspondence. Retina. 2020;40(4):e13. https:\/\/doi.org\/10.1097\/IAE.0000000000002710.","journal-title":"Retina"},{"issue":"1","key":"1358_CR44","doi-asserted-by":"publisher","DOI":"10.16964\/er.v1i1.42","volume":"1","author":"MW Stewart","year":"2011","unstructured":"Stewart MW. What are the half-lives of ranibizumab and aflibercept (VEGF trap-eye) in human eyes? Calculations with a mathematical model. Eye Rep. 2011;1(1):e5. https:\/\/doi.org\/10.16964\/er.v1i1.42.","journal-title":"Eye Rep"},{"issue":"5","key":"1358_CR45","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/j.ophtha.2015.12.030","volume":"123","author":"FG Holz","year":"2016","unstructured":"Holz FG, Dugel PU, Weissgerber G, et al. Single-chain antibody fragment VEGF inhibitor RTH258 for neovascular age-related macular degeneration: a randomized controlled study. Ophthalmology. 2016;123(5):1080\u20139. https:\/\/doi.org\/10.1016\/j.ophtha.2015.12.030.","journal-title":"Ophthalmology"},{"issue":"11","key":"1358_CR46","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1002\/jcph.2290","volume":"63","author":"M Kagedal","year":"2023","unstructured":"Kagedal M, Alskar O, Petersson K, et al. Population pharmacokinetics of ranibizumab delivered via the Port Delivery System implanted in the eye in patients with neovascular age-related macular degeneration. J Clin Pharmacol. 2023;63(11):1210\u201320. https:\/\/doi.org\/10.1002\/jcph.2290.","journal-title":"J Clin Pharmacol"},{"issue":"10","key":"1358_CR47","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1097\/IAE.0000000000001493","volume":"37","author":"RL Avery","year":"2017","unstructured":"Avery RL, Castellarin AA, Steinle NC, et al. Systemic pharmacokinetics and pharmacodynamics of intravitreal aflibercept, bevacizumab, and ranibizumab. Retina. 2017;37(10):1847\u201358. https:\/\/doi.org\/10.1097\/IAE.0000000000001493.","journal-title":"Retina"},{"issue":"4","key":"1358_CR48","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.ajo.2012.03.047","volume":"154","author":"TU Krohne","year":"2012","unstructured":"Krohne TU, Liu Z, Holz FG, Meyer CH. Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans. Am J Ophthalmol. 2012;154(4):682-6.e2. https:\/\/doi.org\/10.1016\/j.ajo.2012.03.047.","journal-title":"Am J Ophthalmol"},{"issue":"3","key":"1358_CR49","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1167\/iovs.12-10260","volume":"54","author":"L Xu","year":"2013","unstructured":"Xu L, Lu T, Tuomi L, et al. Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: a population approach. Invest Ophthalmol Vis Sci. 2013;54(3):1616\u201324. https:\/\/doi.org\/10.1167\/iovs.12-10260.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"1358_CR50","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.ajo.2008.05.036","volume":"146","author":"TU Krohne","year":"2008","unstructured":"Krohne TU, Eter N, Holz FG, Meyer CH. Intraocular pharmacokinetics of bevacizumab after a single intravitreal injection in humans. Am J Ophthalmol. 2008;146(4):508\u201312. https:\/\/doi.org\/10.1016\/j.ajo.2008.05.036.","journal-title":"Am J Ophthalmol"},{"issue":"9","key":"1358_CR51","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1097\/IAE.0b013e318217373c","volume":"31","author":"CH Meyer","year":"2011","unstructured":"Meyer CH, Krohne TU, Holz FG. Intraocular pharmacokinetics after a single intravitreal injection of 1.5 mg versus 3.0 mg of bevacizumab in humans. Retina. 2011;31(9):1877\u201384. https:\/\/doi.org\/10.1097\/IAE.0b013e318217373c.","journal-title":"Retina"},{"issue":"13","key":"1358_CR52","first-page":"4936","volume":"48","author":"KG Csaky","year":"2007","unstructured":"Csaky KG, Gordiyenko N, Rabena MG, Avery RL. Pharmacokinetics of intravitreal bevacizumab in humans. Invest Ophthalmol Vis Sci. 2007;48(13):4936.","journal-title":"Invest Ophthalmol Vis Sci"}],"container-title":["Ophthalmology and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40123-026-01358-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40123-026-01358-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40123-026-01358-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T12:42:26Z","timestamp":1775133746000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40123-026-01358-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":52,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["1358"],"URL":"https:\/\/doi.org\/10.1007\/s40123-026-01358-5","relation":{},"ISSN":["2193-8245","2193-6528"],"issn-type":[{"value":"2193-8245","type":"print"},{"value":"2193-6528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]},"assertion":[{"value":"14 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Richard Avery has been a consultant for 4D Molecular Therapeutics, AbbVie, Alcon, Alimera, Allergan, Amgen, AsclepiX, Astellas, Aviceda, Bausch\u2009+\u2009Lomb, Cardinal Health, Clearside Biomedical, Coherus, EyePoint, ForwardVue, Genentech, Inc., Glaukos, Imprimis, InFocus Capital Partners, Ingenia, Kriya, KYS Vision, Merit, Novartis, NVasc, Ocular Therapeutix, Outlook, Pixium, Pr3vent AI, PulseMedica, Regenxbio, Replenish, Re-Vana, Santen, Tenpoint Therapeutics, Vial, and Visionary Ventures; holds stock in AbbVie, Adverum, Alcon, Aldeyra, Apellis, EyePoint, InFocus Capital Partners, Iveric Bio, Kodiak Sciences, Novartis, NVasc, Ocular Therapeutix, Outlook, Regeneron, Replenish, Re-Vana, Verana Health, and Visionary Ventures; holds stock options in Aviceda, ForwardVue, Ingenia, KYS Vision, and NVasc and has been on the speakers\u2019 bureau for Genentech, Inc. Cheikh Diack, Nancy Holekamp, and Mustapha Lhor are employees of F. Hoffmann-La Roche Ltd. Florie Mar and Katie Maass are employees of Genentech, Inc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}