{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:32:55Z","timestamp":1793424775231,"version":"4.5.0"},"reference-count":71,"publisher":"S.C. JURNALUL PENTRU MEDICINA SI VIATA S.R.L","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.25122\/jml-2025-0180","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T14:13:18Z","timestamp":1771251198000},"page":"984-993","source":"Crossref","is-referenced-by-count":4,"title":["Ocular gene therapy as a sustained drug delivery system: pharmacokinetic and genokinetic perspectives"],"prefix":"10.25122","volume":"18","author":[{"given":"Carmen-Ecaterina","family":"Leferman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Pharmacology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alin Dumitru","family":"Ciubotaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Biochemistry, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10755","reference":[{"issue":"3","key":"ref1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3390\/pharmaceutics12030269","article-title":"Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations","volume":"12","author":"Varela-Fern\u00e1ndez R, D\u00edaz-Tom\u00e9 V, Luaces-Rodr\u00edguez A, Conde-Penedo A, Garc\u00eda-Otero X, Luzardo-\u00c1lvarez A","year":"2020","unstructured":"1. Varela-Fern\u00e1ndez R, D\u00edaz-Tom\u00e9 V, Luaces-Rodr\u00edguez A, Conde-Penedo A, Garc\u00eda-Otero X, Luzardo-\u00c1lvarez A, Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations, Pharmaceutics, 2020;12(3):269","journal-title":"Pharmaceutics"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.5301\/EJO.2010.6049","article-title":"Blood-retinal barrier","volume":"21","author":"Cunha-Vaz J, Bernardes R, Lobo C","year":"2011","unstructured":"2. Cunha-Vaz J, Bernardes R, Lobo C, Blood-retinal barrier, Eur J Ophthalmol, 2011;21(Suppl 6):S3-9","journal-title":"Eur J Ophthalmol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.preteyeres.2016.12.001","article-title":"Pharmacokinetic aspects of retinal drug delivery","volume":"57","author":"Del Amo EM, Rimpel\u00e4 AK, Heikkinen E, Kari OK, Ramsay E, Lajunen T","year":"2017","unstructured":"3. Del Amo EM, Rimpel\u00e4 AK, Heikkinen E, Kari OK, Ramsay E, Lajunen T, Pharmacokinetic aspects of retinal drug delivery, Prog Retin Eye Res, 2017;57134-185","journal-title":"Prog Retin Eye Res"},{"issue":"8","key":"ref4","doi-asserted-by":"publisher","first-page":"365","DOI":"10.3390\/pharmaceutics11080365","article-title":"Pharmacokinetics of Intravitreal Anti-VEGF Drugs in Age-Related Macular Degeneration","volume":"11","author":"Garc\u00eda-Quintanilla L, Luaces-Rodr\u00edguez A, Gil-Mart\u00ednez M, Mondelo-Garc\u00eda C, Maro\u00f1as O, Mangas-Sanjuan V","year":"2019","unstructured":"4. Garc\u00eda-Quintanilla L, Luaces-Rodr\u00edguez A, Gil-Mart\u00ednez M, Mondelo-Garc\u00eda C, Maro\u00f1as O, Mangas-Sanjuan V, Pharmacokinetics of Intravitreal Anti-VEGF Drugs in Age-Related Macular Degeneration, Pharmaceutics, 2019;11(8):365","journal-title":"Pharmaceutics"},{"issue":"7","key":"ref5","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.oret.2018.01.006","article-title":"Real-world Outcomes of Anti-Vascular Endothelial Growth Factor Therapy in Neovascular Age-Related Macular Degeneration in the United States","volume":"2","author":"Ciulla TA, Huang F, Westby K, Williams DF, Zaveri S, Patel SC","year":"2018","unstructured":"5. Ciulla TA, Huang F, Westby K, Williams DF, Zaveri S, Patel SC, Real-world Outcomes of Anti-Vascular Endothelial Growth Factor Therapy in Neovascular Age-Related Macular Degeneration in the United States, Ophthalmol Retina, 2018;2(7):645-653","journal-title":"Ophthalmol Retina"},{"key":"ref6","author":"U.S. Food and Drug Administration","unstructured":"6. U.S. Food and Drug Administration, Summary review for NDA 022315s000 [Internet], Silver Spring (MD):U.S. Food and Drug Administration, Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2009\/022315s000_sumr.pdf","journal-title":"Summary review for NDA 022315s000 [Internet]"},{"key":"ref7","article-title":"In: Clinical Review Report: Fluocinolone Acetonide Intravitreal Implant (Iluvien): (Knight Therapeutics Inc): Indication: For the treatment of diabetic macular edema (DME) in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure [Internet] [Internet]","author":"Executive Summary","year":"2019","unstructured":"7. Executive Summary, In: Clinical Review Report: Fluocinolone Acetonide Intravitreal Implant (Iluvien): (Knight Therapeutics Inc): Indication: For the treatment of diabetic macular edema (DME) in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure [Internet] [Internet], Canadian Agency for Drugs and Technologies in Health, 2019;Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK551989\/","journal-title":"Canadian Agency for Drugs and Technologies in Health"},{"issue":"8","key":"ref8","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1016\/j.ophtha.2019.03.036","article-title":"The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial","volume":"126","author":"Campochiaro PA, Marcus DM, Awh CC, Regillo C, Adamis AP, Bantseev V","year":"2019","unstructured":"8. Campochiaro PA, Marcus DM, Awh CC, Regillo C, Adamis AP, Bantseev V, The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial, Ophthalmology, 2019;126(8):1141-1154","journal-title":"Ophthalmology"},{"issue":"1","key":"ref9","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s40942-023-00446-z","article-title":"Port delivery system with ranibizumab (Susvimo) recall-What does it mean to the retina specialists","volume":"9","author":"Sharma A, Khanani AM, Parachuri N, Kumar N, Bandello F, Kuppermann BD","year":"2023","unstructured":"9. Sharma A, Khanani AM, Parachuri N, Kumar N, Bandello F, Kuppermann BD, Port delivery system with ranibizumab (Susvimo) recall-What does it mean to the retina specialists, Int J Retina Vitreous, 2023;9(1):6","journal-title":"Int J Retina Vitreous"},{"key":"ref10","author":"Roche to reintroduce Susvimo in the US for people with neovascular age-related macular degeneration (nAMD)","year":"2024","unstructured":"10. Roche to reintroduce Susvimo in the US for people with neovascular age-related macular degeneration (nAMD), [Internet], Basel:F Hoffmann-La Roche Ltd, 2024;[cited 2025 Dec 17] Available from: https:\/\/www.roche.com\/media\/releases\/med-cor-2024-07-08","journal-title":"[Internet]"},{"issue":"5","key":"ref11","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1056\/NEJMra1706910","article-title":"Gene Therapy","volume":"381","author":"High KA, Roncarolo MG","year":"2019","unstructured":"11. High KA, Roncarolo MG, Gene Therapy, N Engl J Med, 2019;381(5):455-464","journal-title":"N Engl J Med"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.omtm.2019.01.008","article-title":"Capsid Modifications for Targeting and Improving the Efficacy of AAV Vectors","volume":"12","author":"B\u00fcning H, Srivastava A","year":"2019","unstructured":"12. B\u00fcning H, Srivastava A, Capsid Modifications for Targeting and Improving the Efficacy of AAV Vectors, Mol Ther Methods Clin Dev, 2019;12248-265","journal-title":"Mol Ther Methods Clin Dev"},{"issue":"21","key":"ref13","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1056\/NEJMoa0802315","article-title":"Safety and efficacy of gene transfer for Leber's congenital amaurosis","volume":"358","author":"Maguire AM, Simonelli F, Pierce EA, Pugh EN, Mingozzi F, Bennicelli J","year":"2008","unstructured":"13. Maguire AM, Simonelli F, Pierce EA, Pugh EN, Mingozzi F, Bennicelli J, Safety and efficacy of gene transfer for Leber's congenital amaurosis, N Engl J Med, 2008;358(21):2240-8","journal-title":"N Engl J Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1146\/annurev-neuro-062012-170304","article-title":"Gene therapy for blindness","volume":"36","author":"Sahel JA, Roska B","year":"2013","unstructured":"14. Sahel JA, Roska B, Gene therapy for blindness, Annu Rev Neurosci, 2013;36467-88","journal-title":"Annu Rev Neurosci"},{"issue":"10097","key":"ref15","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/S0140-6736(17)31868-8","article-title":"Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial","volume":"390","author":"Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A","year":"2017","unstructured":"15. Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial, Lancet, 2017;390(10097):849-860","journal-title":"Lancet"},{"issue":"10045","key":"ref16","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/S0140-6736(16)30371-3","article-title":"Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial","volume":"388","author":"Bennett J, Wellman J, Marshall KA, McCague S, Ashtari M, DiStefano-Pappas J","year":"2016","unstructured":"16. Bennett J, Wellman J, Marshall KA, McCague S, Ashtari M, DiStefano-Pappas J, Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial, Lancet, 2016;388(10045):661-72","journal-title":"Lancet"},{"issue":"5","key":"ref17","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1089\/hum.2011.050","article-title":"Gene transfer for neovascular age-related macular degeneration","volume":"22","author":"Campochiaro PA","year":"2011","unstructured":"17. Campochiaro PA, Gene transfer for neovascular age-related macular degeneration, Hum Gene Ther, 2011;22(5):523-9","journal-title":"Hum Gene Ther"},{"key":"ref18","article-title":"ABBV-RGX-314 therapeutic program","author":"REGENXBIO","unstructured":"18. REGENXBIO, ABBV-RGX-314 therapeutic program, [Internet], Available from: https:\/\/www.regenxbio.com\/therapeutic-programs\/rgx-314\/","journal-title":"[Internet]"},{"key":"ref19","article-title":"REGENXBIO Announces Presentation at the American Academy of Ophthalmology 2025 Annual Meeting","author":"Inc R","unstructured":"19. Inc R, REGENXBIO Announces Presentation at the American Academy of Ophthalmology 2025 Annual Meeting, [Internet], Available from: https:\/\/www.prnewswire.com\/news-releases\/regenxbio-announces-presentation-at-the-american-academy-of-ophthalmology-2025-annual-meeting-302579228.html","journal-title":"[Internet]"},{"key":"ref20","author":"Adverum Biotechnologies Initiates ARTEMIS Phase 3 Study Evaluating Ixo-vec for Wet AMD","unstructured":"20. Adverum Biotechnologies Initiates ARTEMIS Phase 3 Study Evaluating Ixo-vec for Wet AMD, [Internet]. Adverum Biotechnologies, Available from: https:\/\/adverum.com\/press-archive\/adverum-biotechnologies-initiates-artemis-phase-3-study-evaluating-ixo-vec-for-wet-amd\/","journal-title":"[Internet]. Adverum Biotechnologies"},{"key":"ref21","article-title":"A Multi-Center, Randomized, Double-Masked, Active-Comparator-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-Related Macular Degeneration (ARTEMIS) [Internet]","author":"Adverum Biotechnologies Inc","year":"2025","unstructured":"21. Adverum Biotechnologies Inc, A Multi-Center, Randomized, Double-Masked, Active-Comparator-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-Related Macular Degeneration (ARTEMIS) [Internet], clinicaltrials.gov, 2025;Report No.: NCT06856577. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06856577","journal-title":"clinicaltrials.gov"},{"issue":"6","key":"ref22","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1002\/cpt.3230","article-title":"Clinical Pharmacology Perspective on Development of Adeno-Associated Virus Vector-Based Retina Gene Therapy","volume":"115","author":"Ford JL, Karatza E, Mody H, Nagaraja Shastri P, Khajeh Pour S, Yang TY, Swanson M, Chao D, Devineni D","year":"2024","unstructured":"22. Ford JL, Karatza E, Mody H, Nagaraja Shastri P, Khajeh Pour S, Yang TY, Swanson M, Chao D, Devineni D, Clinical Pharmacology Perspective on Development of Adeno-Associated Virus Vector-Based Retina Gene Therapy, Clin Pharmacol Ther, 2024;115(6):1212-1232","journal-title":"Clin Pharmacol Ther"},{"issue":"11","key":"ref23","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1167\/iovs.65.11.28","article-title":"Mathematical Models of Ocular Drug Delivery","volume":"65","author":"Sadeghi A, Subrizi A, Del Amo EM, Urtti A","year":"2024","unstructured":"23. Sadeghi A, Subrizi A, Del Amo EM, Urtti A, Mathematical Models of Ocular Drug Delivery, Invest Ophthalmol Vis Sci, 2024;65(11):28","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.2147\/OPTH.S364200","article-title":"Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses","volume":"16","author":"Ghoraba HH, Akhavanrezayat A, Karaca I, Yavari N, Lajevardi S, Hwang J, Regenold J, Matsumiya W, Pham B, Zaidi M, Mobasserian A, DongChau AT, Or C, Yasar C, Mishra K, Do D, Nguyen QD","year":"2022","unstructured":"24. Ghoraba HH, Akhavanrezayat A, Karaca I, Yavari N, Lajevardi S, Hwang J, Regenold J, Matsumiya W, Pham B, Zaidi M, Mobasserian A, DongChau AT, Or C, Yasar C, Mishra K, Do D, Nguyen QD, Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses, Clin Ophthalmol, 2022;161753-1771","journal-title":"Clin Ophthalmol"},{"issue":"4","key":"ref25","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1111\/brv.12718","article-title":"Humoral immune responses to AAV gene therapy in the ocular compartment","volume":"96","author":"Whitehead M, Osborne A, Yu-Wai-Man P, Martin K","year":"2021","unstructured":"25. Whitehead M, Osborne A, Yu-Wai-Man P, Martin K, Humoral immune responses to AAV gene therapy in the ocular compartment, Biol Rev Camb Philos Soc, 2021;96(4):1616-1644","journal-title":"Biol Rev Camb Philos Soc"},{"issue":"8","key":"ref26","doi-asserted-by":"publisher","first-page":"4612","DOI":"10.1021\/acs.molpharmaceut.5c00155","article-title":"A Semimechanistic Ocular Pharmacokinetic Model for ADVM-022 Gene Therapy Describing the Dose-Exposure Relationship in Monkeys and the Scaling to Human","volume":"22","author":"Hugi F, Vollmer J, Renaud L, Machacek M","year":"2025","unstructured":"26. Hugi F, Vollmer J, Renaud L, Machacek M, A Semimechanistic Ocular Pharmacokinetic Model for ADVM-022 Gene Therapy Describing the Dose-Exposure Relationship in Monkeys and the Scaling to Human, Mol Pharm, 2025;22(8):4612-4623","journal-title":"Mol Pharm"},{"issue":"1","key":"ref27","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1097\/APO.0000000000000362","article-title":"Creating an ocular biofactory: surgical approaches in gene therapy for acquired retinal diseases","volume":"10","author":"Xu D, Khan MA, Ho AC","year":"2021","unstructured":"27. Xu D, Khan MA, Ho AC, Creating an ocular biofactory: surgical approaches in gene therapy for acquired retinal diseases, Asia Pac J Ophthalmol (Phila), 2021;10(1):5-11","journal-title":"Asia Pac J Ophthalmol (Phila)"},{"issue":"1","key":"ref28","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1167\/tvst.9.1.2","article-title":"In Vivo Measurement of the Human Vitreous Chamber Volume Using Computed Tomography Imaging of 100 Eyes","volume":"9","author":"Azhdam AM, Goldberg RA, Ugradar S","year":"2020","unstructured":"28. Azhdam AM, Goldberg RA, Ugradar S, In Vivo Measurement of the Human Vitreous Chamber Volume Using Computed Tomography Imaging of 100 Eyes, Transl Vis Sci Technol, 2020;9(1):2","journal-title":"Transl Vis Sci Technol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"101389","DOI":"10.1016\/j.preteyeres.2025.101389","article-title":"Replacing the vitreous body with hydrogels: Rationale and strategies","volume":"108","author":"Schulz A, Keskar M, Swindle-Reilly KE, Junge V, Parikh BH, Su X","year":"2025","unstructured":"29. Schulz A, Keskar M, Swindle-Reilly KE, Junge V, Parikh BH, Su X, Replacing the vitreous body with hydrogels: Rationale and strategies, Prog Retin Eye Res, 2025;108101389","journal-title":"Prog Retin Eye Res"},{"issue":"3","key":"ref30","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1208\/s12248-010-9183-3","article-title":"Ocular drug delivery","volume":"12","author":"Gaudana R, Ananthula HK, Parenky A, Mitra AK","year":"2010","unstructured":"30. Gaudana R, Ananthula HK, Parenky A, Mitra AK, Ocular drug delivery, AAPS J, 2010;12(3):348-60","journal-title":"AAPS J"},{"issue":"9","key":"ref31","doi-asserted-by":"publisher","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":"Hutton-Smith LA, Gaffney EA, Byrne HM, Maini PK, Schwab D, Mazer NA","year":"2016","unstructured":"31. 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):2941-50","journal-title":"Mol Pharm"},{"issue":"7","key":"ref32","doi-asserted-by":"publisher","first-page":"2770","DOI":"10.1021\/acs.molpharmaceut.8b00280","article-title":"Theoretical Insights into the Retinal Dynamics of Vascular Endothelial Growth Factor in Patients Treated with Ranibizumab, Based on an Ocular Pharmacokinetic\/Pharmacodynamic Model","volume":"15","author":"Hutton-Smith LA, Gaffney EA, Byrne HM, Caruso A, Maini PK, Mazer NA","year":"2018","unstructured":"32. Hutton-Smith LA, Gaffney EA, Byrne HM, Caruso A, Maini PK, Mazer NA, Theoretical Insights into the Retinal Dynamics of Vascular Endothelial Growth Factor in Patients Treated with Ranibizumab, Based on an Ocular Pharmacokinetic\/Pharmacodynamic Model, Mol Pharm, 2018;15(7):2770-2784","journal-title":"Mol Pharm"},{"issue":"9","key":"ref33","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.3390\/ph16091241","article-title":"Suprachoroidal Injection: A Novel Approach for Targeted Drug Delivery","volume":"16","author":"Wu KY, Fujioka JK, Gholamian T, Zaharia M, Tran SD","year":"2023","unstructured":"33. Wu KY, Fujioka JK, Gholamian T, Zaharia M, Tran SD, Suprachoroidal Injection: A Novel Approach for Targeted Drug Delivery, Pharmaceuticals (Basel), 2023;16(9):1241","journal-title":"Pharmaceuticals (Basel)"},{"issue":"8","key":"ref34","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1016\/j.drudis.2019.03.027","article-title":"Targeting drug delivery within the suprachoroidal space","volume":"24","author":"Jung JH, Chae JJ, Prausnitz MR","year":"2019","unstructured":"34. Jung JH, Chae JJ, Prausnitz MR, Targeting drug delivery within the suprachoroidal space, Drug Discov Today, 2019;24(8):1654-1659","journal-title":"Drug Discov Today"},{"issue":"12","key":"ref35","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1080\/17425247.2024.2435461","article-title":"Suprachoroidal drug delivery: a versatile therapeutic platform","volume":"21","author":"Ciulla TA, Cunningham ET","year":"2024","unstructured":"35. Ciulla TA, Cunningham ET, Suprachoroidal drug delivery: a versatile therapeutic platform, Expert Opin Drug Deliv, 2024;21(12):1705-1713","journal-title":"Expert Opin Drug Deliv"},{"key":"ref36","article-title":"European Medicines Agency","author":"Ozurdex: EPAR product information [Internet]","unstructured":"36. Ozurdex: EPAR product information [Internet], European Medicines Agency, Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/ozurdex-epar-product-information_en.pdf"},{"key":"ref37","author":"Drugs@FDA: FDA-Approved Drugs [Internet]","unstructured":"37. Drugs@FDA: FDA-Approved Drugs [Internet], Available from: https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm?event=BasicSearch.process"},{"issue":"1","key":"ref38","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12348-024-00402-4","article-title":"Fluocinolone acetonide 0.2 \u00b5g\/day intravitreal implant in non-infectious uveitis affecting the posterior segment: EU expert user panel consensus-based clinical recommendations","volume":"14","author":"Pleyer U, Pavesio C, Miserocchi E, Heinz C, Devonport H, Lloren\u00e7 V","year":"2024","unstructured":"38. Pleyer U, Pavesio C, Miserocchi E, Heinz C, Devonport H, Lloren\u00e7 V, Fluocinolone acetonide 0.2 \u00b5g\/day intravitreal implant in non-infectious uveitis affecting the posterior segment: EU expert user panel consensus-based clinical recommendations, J Ophthalmic Inflamm Infect, 2024;14(1):22Erratum in: J Ophthalmic Inflamm Infect. 2025 Jan 8;15(1):1 doi: 10.1186\/s12348-024-00450-w","journal-title":"J Ophthalmic Inflamm Infect"},{"issue":"12","key":"ref39","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1167\/iovs.65.12.21","article-title":"A First-Passage Model of Intravitreal Drug Delivery and Residence Time-Influence of Ocular Geometry, Individual Variability, and Injection Location","volume":"65","author":"Lamirande P, Gaffney EA, Gertz M, Maini PK, Crawshaw JR, Caruso A","year":"2024","unstructured":"39. 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","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"ref40","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s40123-023-00838-2","article-title":"VIVEX: A Formula for Calculating Individual Vitreous Volume: A New Approach Towards Tailored Patient Dosing Regime in Intravitreal Therapy","volume":"13","author":"Borkenstein AF, Borkenstein EM, Langenbucher A","year":"2024","unstructured":"40. Borkenstein AF, Borkenstein EM, Langenbucher A, VIVEX: A Formula for Calculating Individual Vitreous Volume: A New Approach Towards Tailored Patient Dosing Regime in Intravitreal Therapy, Ophthalmol Ther, 2024;13(1):205-219","journal-title":"Ophthalmol Ther"},{"issue":"4","key":"ref41","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1167\/iovs.09-3582","article-title":"Vitreous VEGF clearance is increased after vitrectomy","volume":"51","author":"Lee SS, Ghosn C, Yu Z, Zacharias LC, Kao H, Lanni C","year":"2010","unstructured":"41. Lee SS, Ghosn C, Yu Z, Zacharias LC, Kao H, Lanni C, Vitreous VEGF clearance is increased after vitrectomy, Invest Ophthalmol Vis Sci, 2010;51(4):2135-8","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"6","key":"ref42","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1002\/cpt.3230","article-title":"Clinical Pharmacology Perspective on Development of Adeno-Associated Virus Vector-Based Retina Gene Therapy","volume":"115","author":"Ford JL, Karatza E, Mody H, Nagaraja Shastri P, Khajeh Pour S","year":"2024","unstructured":"42. Ford JL, Karatza E, Mody H, Nagaraja Shastri P, Khajeh Pour S, Clinical Pharmacology Perspective on Development of Adeno-Associated Virus Vector-Based Retina Gene Therapy, Clin Pharmacol Ther, 2024;115(6):1212-1232","journal-title":"Clin Pharmacol Ther"},{"issue":"4","key":"ref43","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.ajo.2012.03.047","article-title":"Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans","volume":"154","author":"Krohne TU, Liu Z, Holz FG, Meyer CH","year":"2012","unstructured":"43. 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):682-686.e2","journal-title":"Am J Ophthalmol"},{"issue":"3","key":"ref44","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1167\/iovs.12-10260","article-title":"Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: a population approach","volume":"54","author":"Xu L, Lu T, Tuomi L, Jumbe N, Lu J, Eppler S","year":"2013","unstructured":"44. Xu L, Lu T, Tuomi L, Jumbe N, Lu J, Eppler S, Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: a population approach, Invest Ophthalmol Vis Sci, 2013;54(3):1616-24","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"189","key":"ref45","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1126\/scitranslmed.3005708","article-title":"In vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous","volume":"5","author":"Dalkara D, Byrne LC, Klimczak RR, Visel M, Yin L, Merigan WH","year":"2013","unstructured":"45. Dalkara D, Byrne LC, Klimczak RR, Visel M, Yin L, Merigan WH, In vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous, Sci Transl Med, 2013;5(189):189-ra76","journal-title":"Sci Transl Med"},{"issue":"12","key":"ref46","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1038\/mt.2009.181","article-title":"Inner limiting membrane barriers to AAV-mediated retinal transduction from the vitreous","volume":"17","author":"Dalkara D, Kolstad KD, Caporale N, Visel M, Klimczak RR, Schaffer DV","year":"2009","unstructured":"46. Dalkara D, Kolstad KD, Caporale N, Visel M, Klimczak RR, Schaffer DV, Inner limiting membrane barriers to AAV-mediated retinal transduction from the vitreous, Mol Ther, 2009;17(12):2096-102","journal-title":"Mol Ther"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.addr.2018.03.001","article-title":"The suprachoroidal space as a route of administration to the posterior segment of the eye","volume":"126","author":"Chiang B, Jung JH, Prausnitz MR","year":"2018","unstructured":"47. Chiang B, Jung JH, Prausnitz MR, The suprachoroidal space as a route of administration to the posterior segment of the eye, Adv Drug Deliv Rev, 2018;12658-66","journal-title":"Adv Drug Deliv Rev"},{"issue":"8","key":"ref48","doi-asserted-by":"publisher","first-page":"4433","DOI":"10.1167\/iovs.12-9872","article-title":"Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye","volume":"53","author":"Patel SR, Berezovsky DE, McCarey BE, Zarnitsyn V, Edelhauser HF, Prausnitz MR","year":"2012","unstructured":"48. Patel SR, Berezovsky DE, McCarey BE, Zarnitsyn V, Edelhauser HF, Prausnitz MR, Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye, Invest Ophthalmol Vis Sci, 2012;53(8):4433-41","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"6","key":"ref49","doi-asserted-by":"publisher","first-page":"E517","DOI":"10.1073\/pnas.1218933110","article-title":"Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement","volume":"110","author":"Cideciyan AV, Jacobson SG, Beltran WA, Sumaroka A, Swider M, Iwabe S","year":"2013","unstructured":"49. Cideciyan AV, Jacobson SG, Beltran WA, Sumaroka A, Swider M, Iwabe S, Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement, Proc Natl Acad Sci U S A, 2013;110(6):E517-25","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ref50","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1182\/blood-2013-01-306647","article-title":"Immune responses to AAV vectors: overcoming barriers to successful gene therapy","volume":"122","author":"Mingozzi F, High KA","year":"2013","unstructured":"50. Mingozzi F, High KA, Immune responses to AAV vectors: overcoming barriers to successful gene therapy, Blood, 2013;122(1):23-36","journal-title":"Blood"},{"issue":"9","key":"ref51","doi-asserted-by":"publisher","first-page":"1973","DOI":"10.3390\/pharmaceutics14091973","article-title":"Immune Responses to Gene Editing by Viral and Non-Viral Delivery Vectors Used in Retinal Gene Therapy","volume":"14","author":"Ren D, Fisson S, Dalkara D, Ail D","year":"2022","unstructured":"51. Ren D, Fisson S, Dalkara D, Ail D, Immune Responses to Gene Editing by Viral and Non-Viral Delivery Vectors Used in Retinal Gene Therapy, Pharmaceutics, 2022;14(9):1973","journal-title":"Pharmaceutics"},{"issue":"9","key":"ref52","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1016\/j.ophtha.2019.06.017","article-title":"Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation-Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials","volume":"126","author":"Maguire AM, Russell S, Wellman JA, Chung DC, Yu ZF, Tillman A","year":"2019","unstructured":"52. Maguire AM, Russell S, Wellman JA, Chung DC, Yu ZF, Tillman A, Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation-Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials, Ophthalmology, 2019;126(9):1273-1285","journal-title":"Ophthalmology"},{"issue":"20","key":"ref53","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1056\/NEJMoa1412965","article-title":"Improvement and decline in vision with gene therapy in childhood blindness","volume":"372","author":"Jacobson SG, Cideciyan AV, Roman AJ, Sumaroka A, Schwartz SB, Heon E","year":"2015","unstructured":"53. Jacobson SG, Cideciyan AV, Roman AJ, Sumaroka A, Schwartz SB, Heon E, Improvement and decline in vision with gene therapy in childhood blindness, N Engl J Med, 2015;372(20):1920-6","journal-title":"N Engl J Med"},{"issue":"8","key":"ref54","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1089\/hum.2015.064","article-title":"Antiangiogenic Eye Gene Therapy","volume":"26","author":"Corydon TJ","year":"2015","unstructured":"54. Corydon TJ, Antiangiogenic Eye Gene Therapy, Hum Gene Ther, 2015;26(8):525-37Erratum in: Hum Gene Ther. 2015 Nov;26(11):777. doi: 10.1089\/hum.2015.064.cxn","journal-title":"Hum Gene Ther"},{"key":"ref55","article-title":"A Randomized, Partially Masked, Controlled, Phase 2b/3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD (ATMOSPHERE) [Internet]","author":"AbbVie","year":"2025","unstructured":"55. AbbVie, A Randomized, Partially Masked, Controlled, Phase 2b/3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD (ATMOSPHERE) [Internet], clinicaltrials.gov, 2025;Report No.: NCT04704921. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04704921","journal-title":"clinicaltrials.gov"},{"key":"ref56","article-title":"A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD [Internet]","author":"AbbVie","year":"2025","unstructured":"56. AbbVie, A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD [Internet], clinicaltrials.gov, 2025;Report No.: NCT05407636. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05407636","journal-title":"clinicaltrials.gov"},{"issue":"7","key":"ref57","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1167\/iovs.61.7.1154","article-title":"Phase 1 study of intravitreal gene therapy ADVM-022 for neovascular AMD (OPTIC Trial)","volume":"61","author":"Khanani AM, Kiss S, Turpcu A, Hoang C, Osborne A","year":"2020","unstructured":"57. Khanani AM, Kiss S, Turpcu A, Hoang C, Osborne A, Phase 1 study of intravitreal gene therapy ADVM-022 for neovascular AMD (OPTIC Trial), Invest Ophthalmol Vis Sci, 2020;61(7):1154","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"7","key":"ref58","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1097\/IAE.0000000000003796","article-title":"COMPLEMENT INHIBITION FOR GEOGRAPHIC ATROPHY: Review of Salient Functional Outcomes and Perspective","volume":"43","author":"Spaide RF, Vavvas DG","year":"2023","unstructured":"58. Spaide RF, Vavvas DG, COMPLEMENT INHIBITION FOR GEOGRAPHIC ATROPHY: Review of Salient Functional Outcomes and Perspective, Retina, 2023;43(7):1064-1069","journal-title":"Retina"},{"key":"ref59","article-title":"EXPLORE: A Phase II. Outcomes Assessor-masked, Multicentre, Randomised Study to Evaluate the Safety and Efficacy of Two Doses of GT005 Administered as a Single Subretinal Injection in Subjects With Geographic Atrophy Secondary to Age-related Macular Degeneration [Internet]","author":"Gyroscope Therapeutics Limited","year":"2025","unstructured":"59. Gyroscope Therapeutics Limited, EXPLORE: A Phase II. Outcomes Assessor-masked, Multicentre, Randomised Study to Evaluate the Safety and Efficacy of Two Doses of GT005 Administered as a Single Subretinal Injection in Subjects With Geographic Atrophy Secondary to Age-related Macular Degeneration [Internet], clinicaltrials.gov, 2025;[cited 2025 Dec 19]. Report No.: NCT04437368. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04437368","journal-title":"clinicaltrials.gov"},{"issue":"4","key":"ref60","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1002\/psp4.12597","article-title":"Opportunities and challenges for applying model-informed drug development approaches to gene therapies","volume":"10","author":"Belov A, Schultz K, Forshee R, Tegenge MA","year":"2021","unstructured":"60. Belov A, Schultz K, Forshee R, Tegenge MA, Opportunities and challenges for applying model-informed drug development approaches to gene therapies, CPT Pharmacometrics Syst Pharmacol, 2021;10(4):286-290","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"3","key":"ref61","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.ymthe.2020.01.001","article-title":"Immune Responses to Viral Gene Therapy Vectors","volume":"28","author":"Shirley JL, de Jong YP, Terhorst C, Herzog RW","year":"2020","unstructured":"61. Shirley JL, de Jong YP, Terhorst C, Herzog RW, Immune Responses to Viral Gene Therapy Vectors, Mol Ther, 2020;28(3):709-722","journal-title":"Mol Ther"},{"issue":"7573","key":"ref62","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/nature15818","article-title":"Gene therapy returns to centre stage","volume":"526","author":"Naldini L","year":"2015","unstructured":"62. Naldini L, Gene therapy returns to centre stage, Nature, 2015;526(7573):351-60","journal-title":"Nature"},{"key":"ref63","article-title":"Human Gene Therapy for Retinal Disorders: Guidance for Industry","author":"Food and Drug Administration","year":"2020","unstructured":"63. Food and Drug Administration, Human Gene Therapy for Retinal Disorders: Guidance for Industry, [Internet], Silver Spring (MD):U.S. Food and Drug Administration, 2020;[cited 2025 Dec 19]. Available from: https:\/\/www.fda.gov\/media\/124641\/download","journal-title":"[Internet]"},{"key":"ref64","article-title":"Clinical pharmacokinetics and pharmacodynamics: concepts and applications","author":"Rowland M, Tozer TN","year":"2011","unstructured":"64. Rowland M, Tozer TN, Clinical pharmacokinetics and pharmacodynamics: concepts and applications, Philadelphia:Wolters Kluwer Health\/Lippincott Williams & Wilkins, 2011;"},{"key":"ref65","first-page":"494","author":"Gibaldi M, Perrier D","year":"1982","unstructured":"65. Gibaldi M, Perrier D, Pharmacokinetics 2nd ed rev. and expanded, New York:M Dekker, 1982;494(Drugs and the pharmaceutical sciences)","journal-title":"Pharmacokinetics 2nd ed rev. and expanded"},{"key":"ref66","author":"Routledge & CRC Press [Internet]","unstructured":"66. Routledge & CRC Press [Internet], [cited 2025 Dec 19] Pharmacokinetics, Available from: https:\/\/www.routledge.com\/Pharmacokinetics\/Gibaldi-Perrier\/p\/book\/9780824710422","journal-title":"[cited 2025 Dec 19] Pharmacokinetics"},{"key":"ref67","author":"Tozer PharmD, Thomas N, Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications - Rowland, Malcolm","unstructured":"67. Tozer PharmD, Thomas N, Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications - Rowland, Malcolm, 9780781750097 - AbeBooks [Internet], [cited 2025 Dec 19] Available from: https:\/\/www.abebooks.com\/9780781750097\/Clinical-Pharmacokinetics-Pharmacodynamics-Concepts-Applications-0781750091\/plp","journal-title":"9780781750097 - AbeBooks [Internet]"},{"key":"ref68","article-title":"Long term follow-up after administration of human gene therapy products: guidance for industry","author":"Food and Drug Administration","year":"2020","unstructured":"68. Food and Drug Administration, Long term follow-up after administration of human gene therapy products: guidance for industry, [Internet], Silver Spring (MD):U.S. Food and Drug Administration, 2020;[cited 2025 Dec 19]. Available from: https:\/\/www.fda.gov\/media\/113768\/download","journal-title":"[Internet]"},{"key":"ref69","article-title":"Guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials [Internet]","author":"European Medicines Agency","year":"2025","unstructured":"69. European Medicines Agency, Guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials [Internet], 2025;[cited 2025 Dec 19]. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-quality-non-clinical-clinical-requirements-investigational-advanced-therapy-medicinal-products-clinical-trials_en.pdf"},{"issue":"5","key":"ref70","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1016\/j.ymthe.2025.04.004","article-title":"Gene regulation technologies for gene and cell therapy","volume":"33","author":"Butterfield GL, Reisman SJ, Iglesias N, Gersbach CA","year":"2025","unstructured":"70. Butterfield GL, Reisman SJ, Iglesias N, Gersbach CA, Gene regulation technologies for gene and cell therapy, Mol Ther, 2025;33(5):2104-2122","journal-title":"Mol Ther"},{"issue":"9","key":"ref71","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/nrd.2018.110","article-title":"Gene therapy for neurological disorders: progress and prospects","volume":"17","author":"Deverman BE, Ravina BM, Bankiewicz KS, Paul SM, Sah DWY","year":"2018","unstructured":"71. Deverman BE, Ravina BM, Bankiewicz KS, Paul SM, Sah DWY, Gene therapy for neurological disorders: progress and prospects, Nat Rev Drug Discov, 2018;17(9):641-659Epub 2018 Aug 10. Erratum in: Nat Rev Drug Discov. 2018 Oct;17(10):767. doi: 10.1038\/nrd.2018.158","journal-title":"Nat Rev Drug Discov"}],"container-title":["Journal of Medicine and Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/medandlife.org\/all-issues\/2025\/issue-11-2025\/review-issue-11-2025\/ocular-gene-therapy-as-a-sustained-drug-delivery-system-pharmacokinetic-and-genokinetic-perspectives\/","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T14:13:35Z","timestamp":1771251215000},"score":1,"resource":{"primary":{"URL":"https:\/\/medandlife.org\/all-issues\/2025\/issue-11-2025\/review-issue-11-2025\/ocular-gene-therapy-as-a-sustained-drug-delivery-system-pharmacokinetic-and-genokinetic-perspectives\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":71,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["JMedLife-18-984"],"URL":"https:\/\/doi.org\/10.25122\/jml-2025-0180","relation":{},"ISSN":["1844-3117"],"issn-type":[{"value":"1844-3117","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]}}}