Novel Nanosecond Laser and Ultrasound to Selectively Treat Eye Blood Vessels

新型纳秒激光和超声波选择性治疗眼部血管

• 批准号: 9909610
• 负责人: Yannis Mantas Paulus
• 金额: $ 22.5万
• 依托单位: PHOTOSONOX LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9909610
• 关键词: Age related macular degeneration; Angiography; Animal Model; Atrophic; Blindness; Blood; Blood Vessels; Cataract; Choroid; Choroid Diseases; Choroidal Neovascularization; Clinical; Clinical Research; Collaborations; Contrast Media; Data; Detection; Devices; Disease; Excision; Eye; Feedback; Fundus photography; Glaucoma; Goals; Gold; Hemorrhage; Histopathology; Human; Infection; Injections; Lasers; Macular degeneration; Mediating; Methods; Michigan; Modeling; Neurons; Normal Cell; Optics; Oryctolagus cuniculus; Outcomes Research; Pathologic; Pathologic Neovascularization; Pathway interactions; Patient Care; Patient-Focused Outcomes; Patients; Peripheral; Phase; Photoreceptors; Photosensitization; Photosensitizing Agents; Physiologic pulse; Research; Retina; Retinal Diseases; Safety; Signal Transduction; System; TdT-Mediated dUTP Nick End Labeling Assay; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Ultrasonic Therapy; Ultrasonography; Universities; Vascular Endothelial Growth Factors; Vision; Work; base; clinical translation; clinically relevant; cost; cost efficient; experimental study; eye blood vessel; eye center; human subject; image guided; improved; in vivo; innovation; intravitreal injection; laser photocoagulation; legally blind; medical schools; millisecond; nanosecond; neovascularization; neurosensory; novel; optimal treatments; particle; phase 1 study; proliferative diabetic retinopathy; prototype; real-time images; response; retinal damage; side effect

ABSTRACT / PROJECT SUMMARY Wet age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. Anti-VEGF therapy is currently the gold standard for wet AMD treatment. However, up to 50% of patients in the long term have a suboptimal response to anti-VEGF therapy. A better alternative method for treatment of AMD is urgently needed. We have recently invented a novel, effective, and highly-selective anti- vascular therapy, termed “photo-mediated ultrasound therapy (PUT)”. PUT is based on microcavitations in microvessels produced by synergistically applied laser pulses and ultrasound bursts. As demonstrated by our preliminary studies on clinically relevant animal models, PUT is capable of eliminating the target microvessels in the choroid without causing unwanted damage to the surround tissue, facilitating optimal treatment outcome for patients with AMD. The ultimate goal of our research is to develop and commercialize a new, noninvasive therapeutic technique for safe and efficient treatment of choroidal neovascularization (CNV) in patients with wet AMD. To achieve the ultimate goal, the project streamlines to achieve the technological transition, including the following milestones: (1) to build and verify the Phase I α-prototype on rabbit eye models, (2) to build and verify the Phase II β- prototype for human subjects, (3) to complete clinical studies, and (4) to define the approval pathway with the FDA. In this Phase I research, PhotoSonoX LLC, via an established collaboration with the Kellogg Eye Center at the University of Michigan School of Medicine, will build a clinically ready α-prototype system, and fully test its safety and efficacy to pave the road to clinical studies in Phase II. The hypothesis of the Phase I study is that PUT can precisely remove pathologic microvessels in the eye without causing short-term and long-term damage in the surrounding tissue. To test this hypothesis, the following specific aims will be accomplished: Aim 1. Develop a clinically ready α-prototype PUT system which has a reasonable cost and can be tested on clinically relevant rabbit eyes in Phase I and on human eyes in Phase II. Aim 2. Determine the long-term safety of PUT for treatment of choroidal microvessels on normal rabbits in vivo. Aim 3. Validate the short and long-term efficacy and safety of PUT for treating pathologic choroidal neovascularization in vivo on a rabbit model of AMD. The outcome from this research will be proof- of-concept that the PUT effectively and safely removes pathologic choroidal microvessels to treat AMD. We expect that the proposed PUT device has great potential to transform our care of patients with AMD by facilitating targeted and precise therapy while reducing the treatment burden and side effects.

摘要/项目总结 湿性年龄相关性黄斑变性（AMD）是发达国家中不可逆失明的主要原因。 世界抗VEGF治疗目前是湿性AMD治疗的金标准。然而，高达50%的 患者在长期对抗VEGF治疗具有次优反应。更好的替代方法， AMD的治疗是迫切需要的。我们最近发明了一种新型的，有效的，高选择性的抗- 血管治疗，称为“光介导的超声治疗（PUT）"。PUT是基于微空化， 通过协同应用激光脉冲和超声脉冲产生微血管。正如我们的 在临床相关动物模型的初步研究中，PUT能够消除靶微血管 而不会对周围组织造成不必要的损伤，从而促进最佳治疗效果 对于AMD患者。 我们研究的最终目标是开发一种新的非侵入性治疗技术并将其商业化 安全有效地治疗湿性AMD患者的脉络膜新生血管（CNV）。实现 最终目标是，该项目将实现技术过渡，包括以下里程碑： (1)在兔眼模型上建立和验证第一阶段的α-原型，（2）建立和验证第二阶段的β- 用于人类受试者的原型，（3）完成临床研究，以及（4）定义批准途径 FDA.在第一阶段的研究中，PhotoSonoX LLC通过与凯洛格眼科中心的合作， 在密歇根大学医学院，将建立一个临床准备的α原型系统，并充分测试 其安全性和有效性，为II期临床研究铺平道路。 I期研究的假设是，PUT可以精确地去除眼睛中的病理微血管 而不会对周围组织造成短期和长期损伤。为了验证这一假设， 将实现以下具体目标：目标1。开发一个临床就绪的α原型PUT系统， 具有合理的成本，并且可以在临床相关的兔眼上进行I期试验， 第二阶段。目标二。确定PUT治疗正常人脉络膜微血管的长期安全性 兔子体内目标3.评价PUT治疗病理性高血压的近期和远期疗效及安全性 在AMD的兔模型上的体内脉络膜新血管形成。这项研究的结果将证明- 概念上，PUT有效且安全地去除病理性脉络膜微血管以治疗AMD。我们 我希望提出的PUT设备有很大的潜力，通过改变我们对AMD患者的护理， 有利于靶向和精确治疗，同时减少治疗负担和副作用。