iCAP An Innovative Device to Rapidly Resolve Microbial Keratitis

iCAP 一种快速解决微生物性角膜炎的创新设备

基本信息

批准号：
10253311
负责人：
ANJAL C SHARMA
金额：
$ 46.88万
依托单位：
LYNNTECH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10253311
关键词：
Accident and Emergency department Air Ambulatory Care Facilities Amoeba genus Animal Model Antibiotic Resistance Antibiotics Antimicrobial Resistance Area Bacteria Bacterial Model Blindness Cataract Cell Adhesion Cell Proliferation Cells Cicatrix Clinical Clinical Treatment Clinical Trials Coagulase Collaborations Consumption Cornea Corneal Ulcer Corneal edema Coupled Cytokine Activation DNA Damage Databases Defect Device Designs Devices Diagnosis Disease Distress Edema Emergency Situation Emergency department visit Endophthalmitis Epidermal Growth Factor Receptor Eye Financial Hardship Focal Adhesions Future Gases Genus staphylococcus Health Expenditures Healthcare Healthcare Systems Helium Hour Human Hydrogen Peroxide IL8 gene In Vitro Infection Inflammation Interleukin-10 Interleukin-6 Ions Keratitis Keratoplasty Lead Legal Blindness MAPK3 gene Medical Medical center Microbe Mississippi Modeling Nitrogen Ophthalmologist Ophthalmology Oryctolagus cuniculus Outcome Oxygen PI3K/AKT Patients Penetrating Keratoplasty Perforation Phase Physiologic Intraocular Pressure Plasma Preclinical Testing Proto-Oncogene Proteins c-akt Pseudomonas aeruginosa Regulation Research Resolution Safety Small Business Innovation Research Grant Staphylococcus aureus Streptococcus Viridans Group Streptococcus pneumoniae Thinness Time Treatment Cost Ultraviolet Rays Universities Virus antimicrobial cell motility corneal repair fungus healing improved in vivo in vivo Model innovation microbial preclinical safety prototype regenerative repair repaired

项目摘要

PROJECT SUMMARY Ulcerative keratitis caused by infectious microbes (bacteria, fungi, amoebae and viruses) represents a major area of medical concern. It is one of the most important causes of corneal opacifications, which is the second common cause of legal blindness world-wide after cataracts. In 2010, in the USA alone, 76.5% of the approximately 930,000 doctor’s office and outpatient clinic and 58,000 emergency department visits related to ocular distress and emergencies, resulted in antibiotic prescriptions for microbial keratitis. The total annual financial burden on our healthcare system for keratitis cases was estimated to be $175 million in direct health care expenditures in 2010 and was also estimated to consume over 250,000 annual hours of clinician time. Bacterial keratitis manifests as corneal ulcer, corneal edema and/or hypopyon and can cause significant complications including corneal perforation, corneal thinning, elevated intraocular pressure and progression to endophthalmitis. This could lead to severe clinical outcomes including partial or complete vision loss, necessity for penetrating keratoplasty, corneal grafts, enucleation and evisceration. Although topical and systemic antibiotics are effective in reducing microbial loads in keratitis cases (unless the microbe is resistant to the antibiotic utilized), the time required to resolve the infection is generally quite lengthy. Furthermore, antibiotics are typically ineffective in reducing inflammation and evoking regenerative repair of corneal and/or scleral defects and scarring which may be induced by the infection. In the preceding SBIR Phase I effort, Lynntech, Inc. in collaboration with the University of Mississippi Medical Center has obtained proof-of-concept for the potential clinical utility of an innovative, inexpensive and compact device, termed iCAP to effectively treat microbial keratitis at the point-of-diagnosis. We now propose this follow-on Phase II SBIR effort, where our specific aims are to (1) optimize and finalize iCAP device design, (2) comprehensively elucidate mechanisms of action of iCAP and (3) comprehensively demonstrate pre-clinical safety and efficacy of iCAP using relevant in vivo animal models of microbial keratitis and (4) research FDA requirements to enable IDE application and human trials in future phases of this effort. The successful completion of these specific aims should pave the way for FDA clearance and commercial insertion into ophthalmologic practice of affordable iCAP devices to effectively treat microbial keratitis at the point-of-diagnosis which in turn is likely to sustain high positive impact for the patient populace suffering from microbial keratitis.

项目概要由传染性微生物（细菌、真菌、阿米巴原虫和病毒）引起的溃疡性角膜炎是一种主要的角膜炎。它是引起角膜混浊的最重要原因之一，是第二大原因。 2010 年，仅在美国，就有 76.5% 的人因白内障而失明。约 930,000 名医生办公室和门诊诊所以及 58,000 名急诊科患者就诊眼部不适和紧急情况，导致每年开出抗生素治疗微生物性角膜炎的总数。角膜炎病例给我们的医疗保健系统带来的直接健康经济负担估计为 1.75 亿美元 2010 年的护理支出，估计每年还消耗超过 250,000 个小时的临床医生时间。细菌性角膜炎表现为角膜溃疡、角膜水肿和/或前房积脓，可导致严重的角膜炎。并发症包括角膜穿孔、角膜变薄、眼内压升高以及进展为这可能会导致严重的临床后果，包括部分或完全视力丧失，穿透性角膜移植术、角膜移植术、摘除术和摘除术的必要性，尽管是局部和摘除术。全身性抗生素可有效减少角膜炎病例中的微生物负荷（除非微生物具有抗药性）抗生素的使用），解决感染所需的时间通常相当长。抗生素通常不能有效减少炎症和引起角膜和/或角膜的再生修复。在之前的 SBIR 第一阶段工作中，感染可能引起巩膜缺损和疤痕。 Lynntech, Inc. 与密西西比大学医学中心合作已获得概念验证一种创新、廉价且紧凑的设备（称为 iCAP）的潜在临床实用性，可以有效地在诊断时治疗微生物性角膜炎，我们现在提出这项后续的 II 期 SBIR 工作，其中。我们的具体目标是 (1) 优化并最终确定 iCAP 器件设计，(2) 全面阐明 iCAP的作用机制以及（3）全面证明iCAP的临床前安全性和有效性使用微生物角膜炎的相关体内动物模型，以及 (4) 研究 FDA 要求以启用 IDE 这项工作的未来阶段的应用和人体试验成功完成了这些具体目标。应该为 FDA 批准和商业化进入眼科实践铺平道路 iCAP 设备可在诊断时有效治疗微生物性角膜炎，从而可能持续下去对患有微生物性角膜炎的患者群体产生高度积极影响。