{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T15:27:14Z","timestamp":1785598034796,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006041","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["41536"],"award-info":[{"award-number":["41536"]}],"id":[{"id":"10.13039\/501100006041","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Optceutics Ltd.","award":["41536"],"award-info":[{"award-number":["41536"]}]},{"name":"UK National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital","award":["41536"],"award-info":[{"award-number":["41536"]}]},{"name":"UCL Institute of Ophthalmology","award":["41536"],"award-info":[{"award-number":["41536"]}]},{"name":"Helen Hamlyn Trust","award":["41536"],"award-info":[{"award-number":["41536"]}]},{"name":"Michael and Ilse Katz Foundation","award":["41536"],"award-info":[{"award-number":["41536"]}]},{"name":"Moorfields Eye Charity","award":["41536"],"award-info":[{"award-number":["41536"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>New in vitro prototypes (PK-Eye\u2122) were tested with and without eye movement to understand diffusion and convection effects on intraocular clearance. Port placement in front ((i) ciliary inflow model) and behind the model lens ((ii) posterior inflow model) was used to study bevacizumab (1.25 mg\/50 \u00b5L) and dexamethasone (0.1 mg\/100 \u00b5L) in phosphate-buffered saline (PBS, pH 7.4) and simulated vitreal fluid (SVF). Dexamethasone was studied in a (iii) retinal-choroid-sclera (RCS) outflow model (with ciliary inflow and two outflow pathways). Ciliary vs. posterior inflow placement did not affect the half-life for dexamethasone at 2.0 \u00b5L\/min using PBS (4.7 days vs. 4.8 days) and SVF (4.9 days with ciliary inflow), but it did decrease the half-life for bevacizumab in PBS (20.4 days vs. 2.4 days) and SVF (19.2 days vs. 10.8 days). Eye movement only affected the half-life of dexamethasone in both media. Dexamethasone in the RCS model showed approximately 20% and 75% clearance from the RCS and anterior outflows, respectively. The half-life of the protein was comparable to human data in the posterior inflow model. Shorter half-life values for a protein in a ciliary inflow model can be achieved with other eye movements. The RCS flow model with eye movement was comparable to human half-life data for dexamethasone.<\/jats:p>","DOI":"10.3390\/pharmaceutics14061267","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T03:01:22Z","timestamp":1655348482000},"page":"1267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effects of Flow Hydrodynamics and Eye Movements on Intraocular Drug Clearance"],"prefix":"10.3390","volume":"14","author":[{"given":"Angeliki","family":"Velentza-Almpani","sequence":"first","affiliation":[{"name":"Optceutics Ltd., 28a Menelik Road, London NW2 3RP, UK"},{"name":"Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5105-025X","authenticated-orcid":false,"given":"Nkiruka","family":"Ibeanu","sequence":"additional","affiliation":[{"name":"Optceutics Ltd., 28a Menelik Road, London NW2 3RP, UK"},{"name":"Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK"},{"name":"National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Optceutics Ltd., 28a Menelik Road, London NW2 3RP, UK"},{"name":"Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Redhead","sequence":"additional","affiliation":[{"name":"Optceutics Ltd., 28a Menelik Road, London NW2 3RP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8087-2268","authenticated-orcid":false,"given":"Peng","family":"Tee Khaw","sequence":"additional","affiliation":[{"name":"Optceutics Ltd., 28a Menelik Road, London NW2 3RP, UK"},{"name":"National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Brocchini","sequence":"additional","affiliation":[{"name":"Optceutics Ltd., 28a Menelik Road, London NW2 3RP, UK"},{"name":"Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK"},{"name":"National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-2508","authenticated-orcid":false,"given":"Sahar","family":"Awwad","sequence":"additional","affiliation":[{"name":"Optceutics Ltd., 28a Menelik Road, London NW2 3RP, UK"},{"name":"Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK"},{"name":"National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1852-872X","authenticated-orcid":false,"given":"Yann","family":"Bouremel","sequence":"additional","affiliation":[{"name":"Optceutics Ltd., 28a Menelik Road, London NW2 3RP, UK"},{"name":"Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK"},{"name":"National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"683","DOI":"10.2217\/nnm-2016-0379","article-title":"Drug delivery to the eye: What benefits do nanocarriers offer?","volume":"12","author":"Joseph","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1097\/00006982-200410000-00002","article-title":"Risks of intravitreous injection: A comprehensive review","volume":"24","author":"Jager","year":"2004","journal-title":"Retina"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/s41433-022-01984-w","article-title":"Retina: A unique subspecialty in the biosimilar landscape","volume":"36","author":"Sharma","year":"2022","journal-title":"Eye"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.2147\/OPTH.S180393","article-title":"Biosimilars in ophthalmology: \u201cis there a big change on the horizon\u201d?","volume":"12","author":"Sharma","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ajo.2020.11.017","article-title":"Biosimilars for Retinal Diseases: An Update","volume":"224","author":"Sharma","year":"2021","journal-title":"Am. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s40259-015-0133-6","article-title":"Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters","volume":"29","author":"Strohl","year":"2015","journal-title":"BioDrugs"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ejpb.2020.05.005","article-title":"Preclinical challenges for developing long acting intravitreal medicines","volume":"153","author":"Awwad","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.preteyeres.2010.04.003","article-title":"Intravitreal therapy for neovascular age-related macular degeneration and inter-individual variations in vitreous pharmacokinetics","volume":"29","author":"Laude","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.tibtech.2006.04.001","article-title":"Scientific and regulatory considerations on the immunogenicity of biologics","volume":"24","author":"Shankar","year":"2006","journal-title":"Trends Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Adrianto, M.F., Annuryanti, F., Wilson, C.G., Sheshala, R., and Thakur, R.R.S. (2021). In vitro dissolution testing models of ocular implants for posterior segment drug delivery. Drug Deliv. Transl. Res.","DOI":"10.1007\/s13346-021-01043-z"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ejpb.2015.04.033","article-title":"Evaluation of protein drug stability with vitreous humor in a novel ex-vivo intraocular model","volume":"95","author":"Patel","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Auel, T., Gro\u00dfmann, L., Schulig, L., Weitschies, W., and Seidlitz, A. (2021). The EyeFlowCell: Development of a 3D-Printed Dissolution Test Setup for Intravitreal Dosage Forms. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091394"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1002\/jps.24480","article-title":"The PK-Eye: A Novel In Vitro Ocular Flow Model for Use in Preclinical Drug Development","volume":"104","author":"Awwad","year":"2015","journal-title":"J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ejpb.2020.01.008","article-title":"Validation of hyaluronic acid-agar-based hydrogels as vitreous humor mimetics for in vitro drug and particle migration evaluations","volume":"148","author":"Thakur","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10237-009-0159-0","article-title":"Mathematical model of flow in the vitreous humor induced by saccadic eye rotations: Effect of geometry","volume":"9","author":"Repetto","year":"2010","journal-title":"Biomech. Model Mechanobiol."},{"key":"ref_16","first-page":"281","article-title":"The Vitreous Model\u2014A new in vitro test method simulating the vitreous body Model characterization","volume":"57","author":"Loch","year":"2012","journal-title":"Biomed. Eng.\/Biomed. Tech."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/jps.23808","article-title":"Simulation of drug distribution in the vitreous body after local drug application into intact vitreous body and in progress of posterior vitreous detachment","volume":"103","author":"Loch","year":"2013","journal-title":"J. Pharm Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ejpb.2017.12.019","article-title":"Antibody loaded collapsible hyaluronic acid hydrogels for intraocular delivery","volume":"124","author":"Egbu","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1700255","DOI":"10.1002\/mabi.201700255","article-title":"Comparative Study of In Situ Loaded Antibody and PEG-Fab NIPAAM Gels","volume":"18","author":"Awwad","year":"2018","journal-title":"Macromol. Biosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104993","DOI":"10.1016\/j.ejps.2019.104993","article-title":"In situ antibody-loaded hydrogel for intravitreal delivery","volume":"137","author":"Awwad","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ijpharm.2017.02.047","article-title":"Sustained release ophthalmic dexamethasone: In vitro in vivo correlations derived from the PK-Eye","volume":"522","author":"Awwad","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10237-012-0398-3","article-title":"Saccade movements effect on the intravitreal drug delivery in vitreous substitutes: A numerical study","volume":"12","author":"Modareszadeh","year":"2013","journal-title":"Biomech. Model Mechanobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1023\/A:1022207026982","article-title":"Computer simulation of convective and diffusive transport of controlled-release drugs in the vitreous humor","volume":"20","author":"Stay","year":"2003","journal-title":"Pharm. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1007\/s10439-018-02110-2","article-title":"A Combined Approach for the Analysis of Ocular Fluid Dynamics in the Presence of Saccadic Movements","volume":"46","author":"Ferroni","year":"2018","journal-title":"Ann. Biomed. Eng."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.medengphy.2011.09.011","article-title":"Numerical simulation of the fluid dynamics in vitreous cavity due to saccadic eye movement","volume":"34","author":"Abouali","year":"2012","journal-title":"Med. Eng. Phys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1088\/0031-9155\/55\/2\/008","article-title":"Mixing processes in the vitreous chamber induced by eye rotations","volume":"55","author":"Stocchino","year":"2010","journal-title":"Phys. Med. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1088\/0031-9155\/52\/7\/016","article-title":"Eye rotation induced dynamics of a Newtonian fluid within the vitreous cavity: The effect of the chamber shape","volume":"52","author":"Stocchino","year":"2007","journal-title":"Phys. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103860","DOI":"10.1016\/j.jmbbm.2020.103860","article-title":"Flow dynamics of vitreous humour during saccadic eye movements","volume":"110","author":"Silva","year":"2020","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s11095-010-0356-7","article-title":"Contribution of Saccadic Motion to Intravitreal Drug Transport: Theoretical Analysis","volume":"28","author":"Balachandran","year":"2011","journal-title":"Pharm Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.medengphy.2020.06.005","article-title":"A drug delivery analysis of large molecules in ocular vitreous chamber: Dependency on saccadic movements after intravitreal injection","volume":"82","author":"Ferroni","year":"2020","journal-title":"Med. Eng. Phys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1089\/108076801753162807","article-title":"Review: Practical issues in intravitreal drug delivery","volume":"17","author":"Maurice","year":"2001","journal-title":"J. Ocul. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1146\/annurev-fluid-120710-101058","article-title":"Fluid Mechanics of the Eye","volume":"44","author":"Siggers","year":"2012","journal-title":"Annu. Rev. Fluid Mech."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0014-4835(66)80029-5","article-title":"Posterior Drainage of the Intraocular Fluid from the Vitreous","volume":"5","author":"Hayreh","year":"1966","journal-title":"Exp. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11095-012-0847-9","article-title":"Retina-choroid-sclera permeability for ophthalmic drugs in the vitreous to blood direction: Quantitative assessment","volume":"30","author":"Haghjou","year":"2013","journal-title":"Pharm Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1001\/archopht.1992.01080140115038","article-title":"Evaluation of the Retinal Toxicity and Pharmacokinetics of Dexamethasone after Intravitreal Injection","volume":"110","author":"Kwak","year":"1992","journal-title":"Arch Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1007\/s00417-009-1141-3","article-title":"Diffusion characteristics of vitreous humour and saline solution follow the Stokes Einstein equation","volume":"247","author":"Gisladottir","year":"2009","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1021\/acs.molpharmaceut.5b00849","article-title":"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","volume":"13","author":"Gaffney","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_38","first-page":"6103","article-title":"Bevacizumab diffusion coefficient in vivo measurment of rabbit vitreous humor with fluorescein labeling","volume":"60","author":"Penkova","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Henein, C., Awwad, S., Ibeanu, N., Vlatakis, S., Brocchini, S., Tee Khaw, P., and Bouremel, Y. (2019). Hydrodynamics of intravitreal injections into liquid vitreous substitutes. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11080371"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Castro-Balado, A., Mondelo-Garc\u00eda, C., Gonz\u00e1lez-Barcia, M., Zarra-Ferro, I., Otero-Espinar, F.J., Ruibal-Morell, \u00c1., Aguiar, P., and Fern\u00e1ndez-Ferreiro, A. (2019). Ocular Biodistribution Studies Using Molecular Imaging. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11050237"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Varela-Fern\u00e1ndez, R., D\u00edaz-Tom\u00e9, V., Luaces-Rodr\u00edguez, A., Conde-Penedo, A., Garc\u00eda-Otero, X., Luzardo-\u00c1lvarez, A., Fern\u00e1ndez-Ferreiro, A., and Otero-Espinar, F.J. (2020). Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12030269"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1089\/jop.2007.0111","article-title":"Effect of retinal permeability, diffusivity, and aqueous humor hydrodynamics on pharmacokinetics of drugs in the eye","volume":"24","author":"Krishnamoorthy","year":"2008","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.jconrel.2005.03.010","article-title":"Evaluation of coupled convective\u2013diffusive transport of drugs administered by intravitreal injection and controlled release implant","volume":"105","author":"Park","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wilson, C.G., and Tan, L.E. (2011). Principles of Retinal Drug Delivery from within the Vitreous. Drug Product Development for the Back of the Eye, Springer Science & Business Media.","DOI":"10.1007\/978-1-4419-9920-7_6"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1023\/A:1007517912927","article-title":"Permeability and diffusion in vitreous humor: Implications for drug delivery","volume":"17","author":"Xu","year":"2000","journal-title":"Pharm Res."},{"key":"ref_46","first-page":"391","article-title":"The flow of aqueous humor in the human eye","volume":"80","author":"Brubaker","year":"1982","journal-title":"Trans. Am. Ophthalmol Soc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/BF02569055","article-title":"The blood-ocular barriers: Past, present, and future","volume":"93","year":"1997","journal-title":"Doc. Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1167\/iovs.04-1051","article-title":"Permeability of Retinal Pigment Epithelium: Effects of Permeant Molecular Weight and Lipophilicity","volume":"46","author":"Pitkanen","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","first-page":"747","article-title":"Normal Range of Eye Movement and Its Relationship to Age","volume":"58","author":"Lim","year":"2017","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1037\/0033-2909.124.3.372","article-title":"Eye movements in reading and information processing: 20 years of research","volume":"124","author":"Rayner","year":"1998","journal-title":"Psychol. Bull."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1167\/8.14.21","article-title":"Saccades and microsaccades during visual fixation, exploration, and search: Foundations for a common saccadic generator","volume":"8","author":"Troncoso","year":"2008","journal-title":"J. Vis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/0042-6989(85)90160-9","article-title":"The upper limit of human smooth pursuit velocity","volume":"25","author":"Meyer","year":"1985","journal-title":"Vis. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.visres.2005.06.027","article-title":"Coordination of smooth pursuit and saccades","volume":"46","author":"Erkelens","year":"2006","journal-title":"Vis. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.visres.2008.05.018","article-title":"Turning the world around: Patterns in saccade direction vary with picture orientation","volume":"48","author":"Foulsham","year":"2008","journal-title":"Vis. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3389\/fpsyg.2014.00210","article-title":"Eye movements when viewing advertisements","volume":"5","author":"Higgins","year":"2014","journal-title":"Front. Psychol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3109\/00016488809119441","article-title":"The effect of stimulus predictability and age on human tracking eye movements","volume":"105","author":"Larsby","year":"1988","journal-title":"Acta Otolaryngol."},{"key":"ref_57","unstructured":"Awwad, S., Bouremel, Y., Ibeanu, N., Brocchini, S.J., and Khaw, P.T. (2022, June 11). Artificial Eye Assembly for Studying Ocular Pharmacokinetics. WO2021186191. Available online: https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=WO2021186191&tab=PCTBIBLIO&_cid=P20-KTWYO1-27725-1."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/6\/1267\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:31:50Z","timestamp":1760139110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/6\/1267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,15]]},"references-count":57,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["pharmaceutics14061267"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14061267","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,15]]}}}