Ocular Therapeutic Delivery Through Real-time Endoscopic B-scan OCT-guided Tools and Robotic Assistance

通过实时内窥镜 B 扫描 OCT 引导工具和机器人辅助进行眼部治疗

• 批准号: 9762113
• 负责人: KAREN MARGARET JOOS
• 金额: $ 39.38万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762113
• 关键词: Accelerometer; Address; Affect; Aging; Anatomy; Biological; Blindness; Cells; Climacteric; Clinical Trials; Disease; Economic Burden; Evaluation; Extravasation; Family suidae; Funding; Future; Genes; Goals; Image; Image-Guided Surgery; Imagery; Inherited; Injections; Investigational New Drug Application; Investigational Therapies; Laparoscopic Surgical Procedures; Laser In Situ Keratomileusis; Location; Manuals; Measurement; Measures; Methods; Microscope; Modeling; Molecular; Monitor; Motion; Needles; Operative Surgical Procedures; Optical Coherence Tomography; Outcome; Perception; Physiological; Population; Preventive; Procedures; Protocols documentation; Reflux; Research; Research Personnel; Resources; Retinal; Retinal Diseases; Retinal Perforations; Robot; Robotics; Role; Safety; Scanning; Stem cells; Supportive care; Surgeon; System; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Therapeutic procedure; Thick; Time; Tissues; Translating; Tremor; Vision; Vision Disorders; Visual impairment; Vitrectomy; Work; age related; base; cost; cost effective; design; effective therapy; gene replacement therapy; gene therapy; image guided; improved; infancy; instrument; minimally invasive; negative affect; new technology; novel; pre-clinical; preservation; prevent; regenerative; robot assistance; robotic system; skills; subretinal injection; therapeutic target; tool

Project Summary Therapeutic protocols using gene therapy or stem cells for treating ocular diseases are still in their infancy, but promise a paradigm shift in treating a variety of visual disorders. Functional cellular preservation is expected to reduce progression of vision impairment, thereby reducing suffering and economic burden. With an aging world population, developing efficient and cost-effective therapies for age-related ocular diseases have become critical. Although less common, inherited retinal disorders cause untreatable vision loss in the young with only supportive care available. New molecular therapeutic agents for these and other blinding diseases present a potential for sight preservation. However, robust translatable injection techniques to enable pre-clinical researchers and clinicians to visualize and accurately deliver therapies to the favored subretinal location are lacking. A safe and accurate subretinal injection procedure is hampered by lack of simultaneous real-time visualization of the cross-sectional retinal layers and the needle tip. Moreover, subretinal injections require extreme accuracy and steadiness beyond the physiological tremor of most surgeons. Due to these perception and technical challenges, the current injection technique may disrupt adjacent anatomical structures. In addition, agent or cells may be injected into the incorrect layer or reflux through the internal retinal hole into the vitreous cavity. Such complications may negatively affect potential vision preservation. The reliability and safety of delivering ocular therapeutics are ongoing FDA concerns, which may affect advancement of the dramatically increasing treatments with >80 Investigational New Drug applications in 2015. Our goal is to directly address the FDA concerns by offering solutions to the critical accuracy barriers of perception and maneuverability by using a novel concept of a direct approach for subretinal injections using needles equipped with B-scan optical coherence tomography (OCT)-guided visualization and by using robotic assistance with online segmentation for localized therapeutic delivery. Our main hypothesis is that the proposed approach with technological augmentation of surgeons’ visualization and manipulation skills for subretinal injections will enable a less invasive, more accurate, and safer therapeutic delivery procedure for ocular diseases. Aim I of our research includes the merging of novel B-scan OCT-guided needles with robotic assistance to achieve therapeutic delivery with minimal anatomical disruption. Aim II of our research includes testing our hypothesis by translating our systems to a preclinical porcine model to evaluate the role of visualization and maneuver augmentation in improving accuracy and time efficiency. This proposed work will develop efficacious OCT image-guided robotic-assisted surgical technologies and methods to enable the accurate delivery, of biologicals being discovered for future preventive, therapeutic and regenerative ocular treatments, with reduced procedural complexity and time.

项目概要 使用基因疗法或干细胞治疗眼部疾病的治疗方案仍处于起步阶段，但是 有望改变治疗各种视觉疾病的范式。功能性细胞保存预计将 减少视力障碍的进展，从而减少痛苦和经济负担。随着世界老龄化 人口，开发有效且具有成本效益的治疗方法来治疗与年龄相关的眼病已成为 批判的。虽然不太常见，但遗传性视网膜疾病会导致年轻人无法治愈的视力丧失，只有 提供支持性护理。针对这些和其他致盲疾病的新分子治疗剂提出了 保护视力的潜力。然而，强大的可转化注射技术可以使临床前 研究人员和临床医生能够将治疗可视化并准确地传递到首选的视网膜下位置 缺乏。由于缺乏同步实时信息，安全而准确的视网膜下注射程序受到阻碍 横截面视网膜层和针尖的可视化。此外，视网膜下注射需要 极高的准确性和稳定性超出了大多数外科医生的生理震颤。由于这些认知 和技术挑战，当前的注射技术可能会破坏邻近的解剖结构。在 此外，药剂或细胞可能被注射到不正确的层中或通过内部视网膜孔回流到视网膜中。 玻璃体腔。此类并发症可能会对潜在的视力保护产生负面影响。可靠性和 提供眼部治疗药物的安全性是 FDA 持续关注的问题，这可能会影响眼科治疗的进展 2015 年，治疗方法大幅增加，新药申请超过 80 种。我们的目标是 通过提供解决感知和准确度关键障碍的解决方案来直接解决 FDA 的担忧 通过使用配备针头进行视网膜下注射的直接方法的新概念来实现可操作性 通过 B 扫描光学相干断层扫描 (OCT) 引导可视化并使用机器人辅助 用于局部治疗交付的在线分段。我们的主要假设是所提出的方法 随着外科医生视网膜下注射可视化和操作技能的技术增强， 为眼部疾病提供侵入性更小、更准确、更安全的治疗递送程序。我的目标是 我们的研究包括将新型 B 扫描 OCT 引导针与机器人辅助相结合，以实现 以最小的解剖结构破坏进行治疗。我们研究的目标 II 包括检验我们的假设 通过将我们的系统转化为临床前猪模型来评估可视化和机动的作用 增强准确性和时间效率。这项拟议的工作将开发有效的 OCT 图像引导机器人辅助手术技术和方法，以实现准确交付 正在发现用于未来预防、治疗和再生眼部治疗的生物制品，其中 减少程序复杂性和时间。