iCAP An Innovative Device to Rapidly Resolve Microbial Keratitis

 描述(申请人提供)：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医学关注的一个主要领域。它是导致角膜混浊的最重要原因之一，是仅次于白内障的全球第二大法定致盲原因。2010年，仅在美国，在约930,000个医生办公室和门诊部以及58,000个与眼部窘迫和紧急情况有关的急诊科就诊中，有76.5%的人因微生物性角膜炎而开出抗生素处方。2010年，我们的医疗系统每年因角膜炎病例造成的总财务负担估计为1.75亿美元的直接医疗支出，并估计每年消耗超过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/或色素沉着，可导致严重的并发症，包括角膜穿孔、角膜变薄、眼压升高和发展为眼内炎。这可能导致严重的临床后果，包括部分或完全视力丧失，需要穿透性角膜移植，角膜移植，眼球摘除和内脏摘除。虽然局部和全身抗生素在减少角膜炎病例中的微生物负荷方面是有效的(除非微生物对所使用的抗生素具有抗药性)，但解决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/或巩膜缺陷的再生修复以及感染可能导致的瘢痕形成方面通常无效。Lynntech公司与密西西比大学医学中心合作，提议开发一种名为ICAP的创新、廉价和紧凑的设备，以在诊断时有效治疗微生物角膜炎。这个设备 将被设计成快速、无反应地显著减少或完全消除细菌 负荷与感染微生物种类的抗菌素敏感性状态无关。此外，ICAP有可能同时触发某些细胞信号通路，从而改善感染引起的角膜和巩膜缺损的再生。在这项第一阶段的SBIR工作中，我们的具体目标是(1)设计和制造ICAP设备原型，(2)利用体外微生物和哺乳动物细胞培养技术，获得可能在体内有效的ICAP设备操作参数的中试范围，(3)证明ICAP可以显著减少或消除细菌负荷，并协调修复相关体内细菌性角膜炎兔眼感染所致的角膜/巩膜缺损。这些具体目标的成功完成应该会证明这种创新的新微生物角膜炎治疗方法的充分可行性，并将使我们能够在未来的第二阶段工作中实施更全面的技术开发和商业化推进。ICAP设备的最终商用很可能对患有微生物角膜炎的患者群体产生高度积极的影响。

 DESCRIPTION (provided by applicant): 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 microbil 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 th infection is generally quite lengthy. Furthermore, antibiotics are typically ineffective in reducin inflammation and evoking regenerative repair of corneal and/or scleral defects and scarring which may be induced by the infection. Lynntech, Inc. in collaboration with the University of Mississippi Medical Center proposes to develop an innovative, inexpensive and compact device, termed iCAP to effectively treat microbial keratitis at the point-of-diagnosis. This device will be engineered to rapidly and reagentlessly significantly reduce or totally eliminate bacterial loads regardless of antimicrobial susceptibility status of the infecting microbial species. Furthermore, iCAP has the potential to simultaneously trigger certain cellular signaling pathways which could result in improved regeneration of corneal and scleral defects induced by the infection. During this Phase I SBIR effort, our specific aims are to (1) design and fabricate prototype iCAP devices, (2) utilize in vitro microbial and mammalian cell culture techniques to obtain pilot ranges of iCAP device operating parameters likely to be effective in vivo and (3) demonstrate that iCAP can significantly reduce or eliminate bacterial loads and orchestrate healing of infection induced corneal/scleral defects in a relevant in vivo rabbit eye model of bacterial keratitis. The successful completion of these specific aims should demonstrate ample feasibility of this innovative new microbial keratitis treatment approach, and will enable us to execute more comprehensive technology development and commercialization thrusts in a future follow-on Phase II effort. The eventual commercial availability of iCAP devices is likely to sustai high positive impact for the patient populace suffering from microbial keratitis.