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

项目摘要 使用基因疗法或干细胞治疗眼科疾病的治疗方案仍处于初级阶段，但 承诺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 减少视力障碍的进展，从而减少痛苦和经济负担。面对老龄化的世界 人口，开发有效和成本效益高的治疗年龄相关眼病的方法已经成为 危急时刻。虽然不太常见，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一种 潜在的视力保护。然而，强大的可翻译注射技术能够实现临床前 研究人员和临床医生要将治疗可视化并准确地提供到最喜欢的视网膜下位置 缺乏。安全和准确的视网膜下注射程序因缺乏同步实时而受到阻碍 视网膜横切面各层和针尖的可视化。此外，视网膜下注射需要 极高的精确度和稳定性，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，目前的注射技术可能会破坏邻近的解剖结构。在……里面 此外，试剂或细胞可能被注射到错误的层中，或通过视网膜内孔回流到 玻璃体腔。这种并发症可能会对潜在的视力保护产生负面影响。它的可靠性和 眼科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，通过80项研究性新药申请大幅增加了治疗。我们的目标是 通过提供感知和识别的关键准确性障碍的解决方案，直接解决FDA的关切 使用配备的针头进行视网膜下注射的新概念的可操作性 使用B超光学相干断层扫描(OCT)引导的可视化，并使用机器人辅助 用于局部治疗交付的在线分割。我们的主要假设是，拟议的方法 随着外科医生视网膜下注射的可视化和操作技能的技术增强， 为眼科疾病提供一种侵入性更小、更准确和更安全的治疗程序。目标I： 我们的研究包括将新型B超OCT导引针与机器人辅助相结合，以实现 以最小的解剖破坏进行治疗性交付。我们研究的目标二包括检验我们的假设 通过将我们的系统转换为临床前猪模型来评估可视化和机动的作用 在提高准确度和时间效率方面的增强。这项拟议的工作将开发出有效的OCT 图像引导的机器人辅助外科手术技术和方法，以实现准确的 正在发现用于未来预防、治疗和再生眼科治疗的生物制品， 降低了程序复杂性和时间。

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.