iCAP An Innovative Device to Rapidly Resolve Microbial Keratitis

项目总结 由传染性微生物(细菌、真菌、阿米巴和病毒)引起的溃疡性角膜炎是一种主要的 医学关注的领域。它是导致角膜混浊的最重要的原因之一，这是第二大原因。 后白内障是世界范围内法律致盲的常见原因。2010年，仅在美国，76.5%的 大约930,000个医生办公室和门诊部以及58,000个急诊科就诊与 眼部不适和紧急情况，导致抗生素处方治疗微生物角膜炎。年度总额 在直接健康方面，角膜炎病例给我们的医疗保健系统造成的财政负担估计为1.75亿美元 2010年的医疗支出，估计每年消耗超过250,000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/或疱疹过少，可引起明显的 并发症包括角膜穿孔、角膜变薄、眼压升高和进展为 眼内炎。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、角膜移植、眼球摘除和内脏摘除的必要性。尽管话题很多， 全身抗生素在减少角膜炎患者的微生物负荷方面是有效的(除非微生物具有耐药性 对于所使用的抗生素)，消除感染所需的时间通常相当长。此外， 抗生素在减少炎症和促进角膜和/或再生修复方面通常无效 感染可能导致的巩膜缺陷和瘢痕形成。在前面的SBIR阶段I工作中， Lynntech，Inc.与密西西比大学医学中心合作获得了概念验证 对于一种创新、廉价和紧凑的设备的潜在临床应用，称为ICAP，以有效地 在诊断时治疗微生物角膜炎。我们现在提出这项第二阶段SBIR的后续工作，其中 我们的具体目标是(1)优化和最终确定ICAP设备设计，(2)全面阐明 ICAP的作用机制；(3)全面论证ICAP的临床前安全性和有效性 使用相关的体内微生物角膜炎动物模型和(4)研究FDA的要求以启用IDE 在这项工作的未来阶段进行应用和人体试验。这些具体目标的圆满完成 应为FDA批准和商业插入负担得起的眼科实践铺平道路 ICAP设备在诊断时有效治疗微生物角膜炎，而这种角膜炎又可能持续 对患有微生物角膜炎的患者人群有很高的积极影响。

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.