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(2025). Advancing Ocular Gene Therapy: A Machine Learning Approach to Enhance Delivery, Uptake and Gene Expression. Drug Discov. Today, 30.","DOI":"10.1016\/j.drudis.2025.104359"},{"key":"ref_2","first-page":"1760","article-title":"Intraocular Route of AAV2 Vector Administration Defines Humoral Immune Response and Therapeutic Potential","volume":"14","author":"Li","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"542","DOI":"10.4103\/NRR.NRR-D-24-00797","article-title":"Innovative Gene Delivery Systems for Retinal Disease Therapy","volume":"21","author":"Wu","year":"2026","journal-title":"Neural Regen. Res."},{"key":"ref_4","first-page":"2535","article-title":"Adenovirus Vector-Mediated in Vivo Gene Transfer into Adult Murine Retina","volume":"35","author":"Bennett","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Drag, S., Dotiwala, F., and Upadhyay, A.K. (2023). Gene Therapy for Retinal Degenerative Diseases: Progress, Challenges, and Future Directions. Investig. Ophthalmol. Vis. Sci., 64.","DOI":"10.1167\/iovs.64.7.39"},{"key":"ref_6","unstructured":"Bennett, J., and Maguire, A.M. (2023). SECTION 4 Translational Basic Science 36 Gene Therapy for Retinal Disease. Ryan\u2019s Retina, Elsevier."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ameri, H., Kesavamoorthy, N., and Bruce, D.N. (2023). Frequency and Pattern of Worldwide Ocular Gene Therapy Clinical Trials up to 2022. Biomedicines, 11.","DOI":"10.3390\/biomedicines11123124"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.4103\/ijo.IJO_3117_20","article-title":"Gene Therapy in Retinal Diseases: A Review","volume":"69","author":"Dhurandhar","year":"2021","journal-title":"Indian J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41591-024-03454-0","article-title":"Gene Therapy Targets the Retina to Treat Eye Disease","volume":"31","author":"Arnold","year":"2025","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","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","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/aos.14249","article-title":"Subretinal Surgery: Functional and Histological Consequences of Entry into the Subretinal Space","volume":"97","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1038\/eye.2017.158","article-title":"Technique of Retinal Gene Therapy: Delivery of Viral Vector into the Subretinal Space","volume":"31","author":"Xue","year":"2017","journal-title":"Eye"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Varin, J., Morival, C., Maillard, N., Adjali, O., and Cronin, T. (2021). Risk Mitigation of Immunogenicity: A Key to Personalized Retinal Gene Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312818"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Taylor, A.W., Hsu, S., and Ng, T.F. (2021). The Role of Retinal Pigment Epithelial Cells in Regulation of Macrophages\/Microglial Cells in Retinal Immunobiology. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.724601"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/jleuko\/qiac016","article-title":"Ocular Immune Privilege and Retinal Pigment Epithelial Cells","volume":"113","author":"Du","year":"2023","journal-title":"J. Leukoc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1097\/IAE.0000000000002609","article-title":"Surgical Technique for Subretinal Gene Therapy in Humans with Inherited Retinal Degeneration","volume":"39","author":"Davis","year":"2019","journal-title":"Retina"},{"key":"ref_17","unstructured":"Kay, C. (2022). SECTION 4 Investigational Surgery and Techniques Subretinal Gene Therapy Delivery. Operative Techniques in Vitreoretinal Surgery, Elsevier."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3220","DOI":"10.1016\/j.ymthe.2024.07.016","article-title":"A Systematic Review of Immunosuppressive Protocols Used in AAV Gene Therapy for Monogenic Disorders","volume":"32","author":"Vrellaku","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.oret.2020.01.023","article-title":"Surgical Techniques for the Subretinal Delivery of Pediatric Gene Therapy","volume":"4","author":"Fan","year":"2020","journal-title":"Ophthalmol. Retin."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1097\/IAE.0000000000001646","article-title":"Intraoperative Use of Microscope-Integrated Optical Coherence Tomography for Subretinal Gene Therapy Delivery","volume":"39","author":"Gregori","year":"2019","journal-title":"Retina"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4901","DOI":"10.1172\/JCI129085","article-title":"AAV8-Vectored Suprachoroidal Gene Transfer Produces Widespread Ocular Transgene Expression","volume":"129","author":"Ding","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ladha, R., Caspers, L.E., Willermain, F., and de Smet, M.D. (2022). Subretinal Therapy: Technological Solutions to Surgical and Immunological Challenges. Front. Med., 9.","DOI":"10.3389\/fmed.2022.846782"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.oret.2021.03.016","article-title":"Perifoveal Chorioretinal Atrophy after Subretinal Voretigene Neparvovec-Rzyl for RPE65-Mediated Leber Congenital Amaurosis","volume":"6","author":"Gange","year":"2022","journal-title":"Ophthalmol. Retina"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1136\/bjophthalmol-2021-321023","article-title":"Development of Retinal Atrophy after Subretinal Gene Therapy with Voretigene Neparvovec","volume":"107","author":"Reichel","year":"2023","journal-title":"Br. J. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1136\/bjo-2022-321488","article-title":"Subretinal Deposits in Young Patients Treated with Voretigene Neparvovec-Rzyl for RPE65-Mediated Retinal Dystrophy","volume":"107","author":"Lopez","year":"2023","journal-title":"Br. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Price, K.W., Pennesi, M.E., Lauer, A.K., and Bailey, S.T. (2022). Iatrogenic Choroidal Neovascularization Associated with Subretinal Gene Therapy Surgery. Am. J. Ophthalmol. Case Rep., 27.","DOI":"10.1016\/j.ajoc.2022.101677"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1159\/000522110","article-title":"Controlled Subretinal Injection Pressure Prevents Damage in Pigs","volume":"245","author":"Olufsen","year":"2022","journal-title":"Ophthalmologica"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Dormegny, L., Studer, F., Sauer, A., Ballonzoli, L., Speeg-Schatz, C., Bourcier, T., Dollfus, H., and Gaucher, D. (2024). Could Internal Limiting Membrane Peeling before Voretigen Neparvovec-Ryzl Subretinal Injection Prevent Focal Chorioretinal Atrophy?. Heliyon, 10.","DOI":"10.1016\/j.heliyon.2024.e25154"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Takahashi, K., Morizane, Y., Hisatomi, T., Tachibana, T., Kimura, S., Hosokawa, M.M., Shiode, Y., Hirano, M., Doi, S., and Toshima, S. (2018). The Influence of Subretinal Injection Pressure on the Microstructure of the Monkey Retina. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0209996"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s41434-021-00294-2","article-title":"Injection Pressure Levels for Creating Blebs during Subretinal Gene Therapy","volume":"29","author":"Scruggs","year":"2022","journal-title":"Gene Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1177\/0018720820916629","article-title":"In Situ Tremor in Vitreoretinal Surgery","volume":"63","author":"Li","year":"2021","journal-title":"Hum. Factors J. Hum. Factors Ergon. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1097\/IAE.0000000000003857","article-title":"Intraoperative Bleb Behavior in Subretinal Gene Augmentation Therapy for Inherited Retinal Diseases","volume":"43","author":"Sisk","year":"2023","journal-title":"Retina"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.omtm.2023.02.006","article-title":"Intravitreal Air Tamponade after AAV2 Subretinal Injection Modifies Retinal EGFP Distribution","volume":"28","author":"Ducloyer","year":"2023","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1097\/ICB.0000000000001143","article-title":"Subretinal air used as a ball valve to stabilize a retinal bleb","volume":"17","author":"Garg","year":"2023","journal-title":"Retin. Cases Brief Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1007\/s11701-023-01699-4","article-title":"IOCT-Guided Simulated Subretinal Injections: A Comparison between Manual and Robot-Assisted Techniques in an Ex-Vivo Porcine Model","volume":"17","author":"Maierhofer","year":"2023","journal-title":"J. Robot Surg."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yang, K., Jin, X., Wang, Z., Fang, Y., Li, Z., Yang, Z., Cong, J., Yang, Y., Huang, Y., and Wang, L. (2022). Robot-Assisted Subretinal Injection System: Development and Preliminary Verification. BMC Ophthalmol., 22.","DOI":"10.1186\/s12886-022-02720-4"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Huang, C., Yang, H., Chen, T., and Chen, C. (2023). Analysis on Key Parameters in Subretinal Injection Facilitating a Predictable and Automated Robot-assisted Treatment in Gene Therapy. Int. J. Med. Robot. Comput. Assist. Surg., 19.","DOI":"10.1002\/rcs.2560"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.1109\/LRA.2024.3375710","article-title":"Autonomous Needle Navigation in Subretinal Injections via IOCT","volume":"9","author":"Zhang","year":"2024","journal-title":"IEEE Robot Autom. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Abid, A., Duval, R., and Boutopoulos, C. (2022). Development and Ex-Vivo Validation of 36G Polyimide Cannulas Integrating a Guiding Miniaturized OCT Probe for Robotic Assisted Subretinal Injections. Biomed. Opt. Express, 13.","DOI":"10.1364\/BOE.448471"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Dehghani, S., Sommersperger, M., Zhang, P., Martin-Gomez, A., Busam, B., Gehlbach, P., Navab, N., Nasseri, M.A., and Iordachita, I. (June, January 29). Robotic Navigation Autonomy for Subretinal Injection via Intelligent Real-Time Virtual IOCT Volume Slicing. Proceedings of the 2023 IEEE International Conference on Robotics and Automation (ICRA), London, UK.","DOI":"10.1109\/ICRA48891.2023.10160372"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Arikan, D., Zhang, P., Sommersperger, M., Dehghani, S., Esfandiari, M., Taylor, R.H., Nasseri, M.A., Gehlbach, P., Navab, N., and Iordachita, I. (2024). Real-Time Deformation-Aware Control for Autonomous Robotic Subretinal Injection under IOCT Guidance. arXiv.","DOI":"10.1109\/ICRA55743.2025.11128595"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"\u0141ajczak, P.M., and Nawrat, Z. (2024). Sharper Vision, Steady Hands: Can Robots Improve Subretinal Drug Delivery? Systematic Review. J. Robot Surg., 18.","DOI":"10.1007\/s11701-024-01991-x"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hejri, A., Chrenek, M.A., Goehring, N.T., Bowland, I.I., Noel, R., Yan, J., Nickerson, J.M., and Prausnitz, M.R. (2025). A Non-Surgical Method for Subretinal Delivery by Trans-Scleral Microneedle Injection. Bioeng. Transl. Med., 10.","DOI":"10.1002\/btm2.10755"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kasetty, V.M., Monsalve, P.F., Sethi, D., Yousif, C., Hessburg, T., Kumar, N., Hamad, A.E., and Desai, U.R. (2024). Cataract Progression after Primary Pars Plana Vitrectomy for Uncomplicated Rhegmatogenous Retinal Detachments in Young Adults. Int. J. Retina Vitreous, 10.","DOI":"10.1186\/s40942-024-00538-4"},{"key":"ref_45","first-page":"429","article-title":"Two-Port Subretinal Injection without Vitrectomy for the Treatment of Bietti Crystalline Dystrophy","volume":"40","author":"Luo","year":"2024","journal-title":"Chin. J. Ocul. Fundus Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1097\/IAE.0000000000002669","article-title":"Nanovitreoretinal Subretinal Gateway Device to Displace Submacular Hemorrhage: Access to the Subretinal Space Without Vitrectomy","volume":"42","author":"Wood","year":"2022","journal-title":"Retina"},{"key":"ref_47","unstructured":"(2025, June 21). Gyroscope Therapeutics Announces FDA Clearance for Orbit Subretinal Delivery System. Available online: https:\/\/www.synconaltd.com\/news-insights\/news\/gyroscope-therapeutics-announces-fda-clearance-for-orbit-subretinal-delivery-system."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1080\/17425247.2021.1867532","article-title":"Biomechanics of Suprachoroidal Drug Delivery: From Benchtop to Clinical Investigation in Ocular Therapies","volume":"18","author":"Hancock","year":"2021","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/j.drudis.2019.03.027","article-title":"Targeting Drug Delivery within the Suprachoroidal Space","volume":"24","author":"Jung","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1089\/jop.2019.0126","article-title":"Suprachoroidal Delivery of Viral and Nonviral Gene Therapy for Retinal Diseases","volume":"36","author":"Kansara","year":"2020","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"692","DOI":"10.3928\/23258160-20180831-07","article-title":"Suprachoroidal Space Alterations Following Delivery of Triamcinolone Acetonide: Post-Hoc Analysis of the Phase 1\/2 HULK Study of Patients with Diabetic Macular Edema","volume":"49","author":"Lampen","year":"2018","journal-title":"Ophthalmic Surg. Lasers Imaging Retin"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1089\/hum.2020.281","article-title":"Host Immune Responses after Suprachoroidal Delivery of AAV8 in Nonhuman Primate Eyes","volume":"32","author":"Chung","year":"2021","journal-title":"Hum. Gene Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Shen, J., Kim, J., Tzeng, S.Y., Ding, K., Hafiz, Z., Long, D., Wang, J., Green, J.J., and Campochiaro, P.A. (2020). Suprachoroidal Gene Transfer with Nonviral Nanoparticles. Sci. Adv., 6.","DOI":"10.1126\/sciadv.aba1606"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1080\/17425247.2023.2256657","article-title":"Alternative Application of an ITrack Microcatheter and Canaloplasty: Case Report and Literature Review","volume":"20","year":"2023","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Naftali Ben Haim, L., and Moisseiev, E. (2021). Drug Delivery via the Suprachoroidal Space for the Treatment of Retinal Diseases. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13070967"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.37765\/ajmc.2023.89324","article-title":"Suprachoroidal Triamcinolone Acetonide Injectable Suspension for Macular Edema Associated with Noninfectious Uveitis: An in-Depth Look at Efficacy and Safety","volume":"29","author":"Yeh","year":"2023","journal-title":"Am. J. Manag. Care"},{"key":"ref_57","unstructured":"(2025, June 21). SCS Microinjector. Available online: https:\/\/clearsidebio.com\/technology\/scs-microinjector\/."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Shen, J., Lima e Silva, R., Zhang, M., Luly, K.M., Hackett, S.F., Tzeng, S.Y., Lowmaster, S.M., Shannon, S.R., Wilson, D.R., and Green, J.J. (2024). Suprachoroidal Gene Transfer with Nonviral Nanoparticles in Large Animal Eyes. Sci. Adv., 10.","DOI":"10.1126\/sciadv.adl3576"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.ophtha.2020.01.006","article-title":"Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis","volume":"127","author":"Yeh","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1136\/bjophthalmol-2020-318019","article-title":"Suprachoroidal CLS-TA for Non-Infectious Uveitis: An Open-Label, Safety Trial (AZALEA)","volume":"106","author":"Henry","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"ref_61","first-page":"1139","article-title":"Extension Study of the Safety and Efficacy of CLS-TA for Treatment of Macular Oedema Associated with Non-Infectious Uveitis (MAGNOLIA)","volume":"106","author":"Khurana","year":"2021","journal-title":"Br. J. Ophthalmol."},{"key":"ref_62","unstructured":"Pitcher, J.D., and Eye, H. (2024). Suprachoroidal Delivery of Investigational ABBV-RGX-314 for Neovascular AMD: Results from the Phase II AAVIATE\u00ae Study, RegenxBio."},{"key":"ref_63","unstructured":"Barakat, M.R. (2023). Suprachoroidal Delivery of Investigational ABBV-RGX-314 for Diabetic Retinopathy: The Phase II ALTITUDE\u00ae Study Dose Levels 1 and 2: One Year Results, RegenxBio."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1177\/24741264211028441","article-title":"Task Force on Intravitreal Injection Supplemental Services Intravitreal Injection Therapy: Current Techniques and Supplemental Services","volume":"5","author":"Lam","year":"2021","journal-title":"J. Vitreoretin. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.4103\/ijo.IJO_82_22","article-title":"Newer Therapeutic Options for Inherited Retinal Diseases: Gene and Cell Replacement Therapy","volume":"70","author":"Battu","year":"2022","journal-title":"Indian J. Ophthalmol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.ophtha.2015.10.025","article-title":"Gene Therapy for Leber Hereditary Optic Neuropathy","volume":"123","author":"Feuer","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Tan, T.-E., Fenner, B.J., Barathi, V.A., Tun, S.B.B., Wey, Y.S., Tsai, A.S.H., Su, X., Lee, S.Y., Cheung, C.M.G., and Wong, T.Y. (2021). Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and Progress. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.795010"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.4103\/1673-5374.306063","article-title":"The Future of Retinal Gene Therapy: Evolving from Subretinal to Intravitreal Vector Delivery","volume":"16","author":"Ross","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Nuzbrokh, Y., Ragi, S.D., and Tsang, S.H. (2021). Gene Therapy for Inherited Retinal Diseases. Ann. Transl. Med., 9.","DOI":"10.21037\/atm-20-4726"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ahn, S., Siontas, O., Koester, J., Krol, J., Fauser, S., and M\u00fcller, D.J. (2024). Magnetically Guided Adeno-Associated Virus Delivery for the Spatially Targeted Transduction of Retina in Eyes. Adv. Healthc. Mater., 13.","DOI":"10.1002\/adhm.202401577"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wang, J.-H., Cui, M., Liu, H., Guo, P., McGowan, J., Cheng, S.-Y., Gessler, D.J., Xie, J., Punzo, C., and Tai, P.W.L. (2025). Cell-Penetrating Peptide-Grafted AAV2 Capsids for Improved Retinal Delivery via Intravitreal Injection. Mol. Ther. Methods Clin. Dev., 33.","DOI":"10.1016\/j.omtm.2025.101426"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Cai, Z., Liu, Y., Zhao, L., Li, X., Zhang, B., Tang, Y., Zhou, T., Zheng, Z., Li, A., and Wei, J. (2024). Novel Intravitreal Retina-Targeting and Immune-Evading Adeno-Associated Virus Capsid Variant. Preprints.","DOI":"10.20944\/preprints202409.2179.v1"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Chiu, W., Lin, T.-Y., Chang, Y.-C., Isahwan-Ahmad Mulyadi Lai, H., Lin, S.-C., Ma, C., Yarmishyn, A.A., Lin, S.-C., Chang, K.-J., and Chou, Y.-B. (2021). An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094534"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.oret.2022.06.013","article-title":"Intravitreal Delivery of RAAV2tYF-CB-HRS1 Vector for Gene Augmentation Therapy in Patients with X-Linked Retinoschisis","volume":"6","author":"Pennesi","year":"2022","journal-title":"Ophthalmol. Retin."},{"key":"ref_75","unstructured":"Taylor, P. (2018). Biogen Bails on AGTC after Ocular Gene Therapy Flunks Trial, Fierce Biotech."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Khanani, A.M., Boyer, D.S., Wykoff, C.C., Regillo, C.D., Busbee, B.G., Pieramici, D., Danzig, C.J., Joondeph, B.C., Major, J.C., and Turpcu, A. (2024). Safety and Efficacy of Ixoberogene Soroparvovec in Neovascular Age-Related Macular Degeneration in the United States (OPTIC): A Prospective, Two-Year, Multicentre Phase 1 Study. eClinicalMedicine, 67.","DOI":"10.1016\/j.eclinm.2023.102394"},{"key":"ref_77","unstructured":"Smith, K. (2024). 4DMT Highlights Robust and Durable Clinical Activity for 4D-150 and Design of 4FRONT Phase 3 Program at 4D-150 Wet AMD Development Day, 4DMT."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"AlEissa, M.M., Alhawsawi, A.A., Alonazi, R., Magharbil, E., Aljahdali, A., AlBalawi, H.B., Alali, N.M., Hameed, S., Abu-Amero, K.K., and Magliyah, M.S. (2025). Advances in Precision Therapeutics and Gene Therapy Applications for Retinal Diseases: Impact and Future Directions. Genes, 16.","DOI":"10.3390\/genes16070847"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jval.2018.09.2841","article-title":"Cost Utility of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease","volume":"22","author":"Zimmermann","year":"2019","journal-title":"Value Health"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ajo.2021.08.009","article-title":"Challenges of Cost-Effectiveness Analyses of Novel Therapeutics for Inherited Retinal Diseases","volume":"235","author":"Jayasundera","year":"2022","journal-title":"Am. J. Ophthalmol."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/12\/10\/1122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:07:50Z","timestamp":1760954870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/12\/10\/1122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,20]]},"references-count":80,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["bioengineering12101122"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering12101122","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,20]]}}}