iCAP An Innovative Device to Rapidly Resolve Microbial Keratitis

项目摘要 由感染性微生物（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 医学关注领域。它是角膜混浊的最重要原因之一， 白内障后全球法律的失明的常见原因。2010年，仅在美国， 约930 000人次到医生办公室和门诊就诊，58 000人次到急诊室就诊， 眼部不适和紧急情况，导致抗生素处方用于微生物角膜炎。年度总 据估计，我们的医疗保健系统因角膜炎病例而造成的直接健康负担为1.75亿美元 2010年的护理支出估计超过250 000小时，估计每年消耗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/或前房积脓，并可引起显著的 并发症包括角膜穿孔、角膜变薄、眼内压升高和进展至 眼内炎这可能导致严重的临床结果，包括部分或完全视力丧失， 穿透性角膜移植术、角膜移植、眼球摘除术和眼内容摘除术的必要性。虽然主题和 全身性抗生素可有效减少角膜炎病例中的微生物负荷（除非微生物具有耐药性 到所用的抗生素），解决感染所需的时间通常相当长。此外，委员会认为， 抗生素在减少炎症和引起角膜和/或角膜上皮的再生修复方面通常是无效的， 巩膜缺损和疤痕，这可能是由感染引起的。在之前的SBIR第一阶段工作中， Lynntech公司与密西西比大学医学中心合作， 对于一种创新的、廉价的、紧凑的设备的潜在临床实用性，称为iCAP， 在诊断时治疗微生物性角膜炎。我们现在提出这一后续的第二阶段SBIR工作，其中 我们的具体目标是（1）优化和完成iCAP器件设计，（2）全面阐明 iCAP的作用机制和（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和（4）研究FDA要求以实现IDE 应用和人体试验在未来阶段的这一努力。这些具体目标的圆满实现 应该为FDA批准和商业插入到眼科实践铺平道路， iCAP设备可在诊断时有效治疗微生物角膜炎，这反过来可能会持续 对患有微生物性角膜炎的患者群体具有高度的积极影响。

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.