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 /项目摘要 与年龄相关的黄斑变性（AMD）是发达的不可逆失明的主要原因 世界。抗VEGF治疗目前是湿AMD治疗的金标准。但是，多达50％ 从长远来看，患者对抗VEGF治疗的反应次好反应。更好的替代方法 迫切需要对AMD的治疗。我们最近发明了一种新颖，有效且高度选择性的抗 - 血管疗法，称为“照片介导的超声疗法（PUT）”。 put是基于微型浪费的 由协同施加的激光脉冲和超声爆发产生的微丝。正如我们所证明的 关于临床相关动物模型的初步研究，PUT能够消除目标微血管 在脉络膜中，不会对周围组织造成不良损害，支持最佳治疗结果 适用于AMD的患者。 我们研究的最终目标是开发和商业化一种新的无创治疗技术 为了安全有效地治疗脉络性新生血管形成（CNV）的湿AMD患者。实现 最终的目标是简化实现技术过渡的项目，包括以下里程碑： （1）在兔眼模型上构建和验证I阶段的α---型，（2）以构建和验证IIβ-相 人类受试者的原型，（3）以完成临床研究，（4）定义了批准途径 FDA。在这阶段I研究中，Photonox LLC通过与Kellogg眼中的建立合作 在密歇根大学医学院将建立一个临床准备就绪的α-型系统，并进行全面测试 在第二阶段的临床研究铺平道路的安全性和效率。 第一阶段研究的假设是，PUT可以精确地去除眼睛中的病理微血管 不会在周围组织中造成短期和长期损害。为了检验这一假设， 将完成以下具体目标：目标1。开发一个临床准备的α-型PUT系统，该系统 具有合理的成本，可以在第一阶段和人眼中对临床相关的兔子眼进行测试 第二阶段。目标2。确定正常脉络膜微血管的长期安全性 体内兔子。目标3。验证治疗病理学的短期和长期效率和安全性 在AMD的兔模型上体内脉络膜新生血管化。这项研究的结果将是证明 - 概念认为，该假期有效，安全地去除病理脉络膜微血管以治疗AMD。我们 预计拟议的PUT设备具有巨大的潜力，可以改变我们对AMD患者的护理 促进靶向和精确的治疗，同时减少治疗燃烧和副作用。