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: 10238850
• 负责人: KAREN MARGARET JOOS
• 金额: $ 38.19万
• 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/10238850
• 关键词: Accelerometer; Address; Affect; Aging; Anatomy; Biological; Blindness; Cell Therapy; Cells; Climacteric; Clinical Trials; Disease; Economic Burden; Evaluation; Extravasation; Funding; Future; Genes; Goals; Image; Image-Guided Surgery; Inherited; Injections; Investigational New Drug Application; Investigational Therapies; Laparoscopic Surgical Procedures; Laser In Situ Keratomileusis; Location; Manuals; Measurement; Measures; Methods; Microscope; Molecular; Monitor; Motion; Needles; Operative Surgical Procedures; Optical Coherence Tomography; Perception; Physiological; Population; Preventive; Procedures; Protocols documentation; Reflux; Research; Research Personnel; Resources; Retina; Retinal Diseases; Retinal Perforations; Robot; Robotics; Role; Safety; Scanning; Supportive care; Surgeon; System; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Therapeutic procedure; Thick; Time; Tissues; Translating; Tremor; Vision; Vision Disorders; Visual impairment; Visualization; Vitrectomy; Work; age related; cost; cost effective treatment; design; gene replacement therapy; gene therapy; image guided; improved; infancy; instrument; minimally invasive; negative affect; new technology; novel; porcine model; pre-clinical; preservation; prevent; regenerative; robot assistance; robotic system; safety outcomes; skills; stem cells; subretinal injection; telemanipulation; 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.

项目摘要 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， 有望在治疗各种视觉障碍方面实现范式转变。功能性细胞保存有望 减少视力损害的进展，从而减少痛苦和经济负担。随着老龄化的世界 人口，开发有效和具有成本效益的治疗与年龄有关的眼病已成为 很危险虽然不太常见，但遗传性视网膜疾病会导致年轻人无法治愈的视力丧失， 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一种新的治疗方法。 保存视力的潜力。然而，强大的可平移注射技术，使临床前 研究人员和临床医生可视化和准确地提供治疗的青睐视网膜下的位置， 缺乏安全和准确的视网膜下注射程序受到缺乏同时实时 视网膜层横截面和针尖的可视化。此外，视网膜下注射需要 超越大多数外科医生生理震颤的极端准确性和稳定性。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，试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。 玻璃体腔这些并发症可能会对潜在的视力保护产生负面影响。的可靠性和 递送眼部治疗剂的安全性是FDA持续关注的问题，这可能影响 2015年，治疗方法大幅增加，研究性新药申请超过80项。我们的目标是 直接解决FDA关注的问题，为感知的关键准确性障碍提供解决方案， 通过使用配备针头的视网膜下注射直接方法的新概念， 通过B扫描光学相干断层扫描（OCT）引导的可视化和使用机器人辅助， 用于局部治疗递送的在线分割。我们的主要假设是， 随着外科医生对视网膜下注射的可视化和操作技能的技术增强， 能够实现用于眼部疾病的侵入性更小、更准确和更安全的治疗递送过程。目标I 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， 以最小的解剖破坏进行治疗递送。我们研究的第二个目的是检验我们的假设 通过将我们的系统转化为临床前猪模型，以评估可视化和操纵的作用， 提高准确性和时间效率。这项拟议的工作将开发有效的OCT 图像引导的机器人辅助手术技术和方法， 生物制剂被发现用于未来的预防性、治疗性和再生性眼部治疗， 降低了程序复杂性和时间。