iCAP An Innovative Device to Rapidly Resolve Microbial Keratitis

 描述（由申请人提供）：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医学关注的主要领域。它是角膜混浊的最重要原因之一，角膜混浊是仅次于白内障的全球法律的盲的第二常见原因。2010年，仅在美国，约930，000名医生的办公室和门诊诊所以及58，000名急诊科就诊中的76.5%与眼窘迫和紧急情况有关，导致抗生素处方用于微生物角膜炎。2010年，我们的医疗保健系统在角膜炎病例方面的直接医疗保健支出估计为1.75亿美元，并且估计每年消耗超过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/或前房积脓，并可引起严重并发症，包括角膜穿孔、角膜变薄、眼内压升高和进展为眼内炎。这可能导致严重的临床结局，包括部分或完全视力丧失，需要穿透性角膜移植术、角膜移植、眼球摘除和眼内容摘除。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引起角膜和/或巩膜缺损的再生修复以及可能由感染诱导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，提出开发一种创新的、廉价的和紧凑的装置，称为iCAP，以在诊断点有效地治疗微生物角膜炎。这个设备 将被设计成快速和无试剂地显著减少或完全消除细菌， 无论感染微生物种类的抗菌药物敏感性状态如何。此外，iCAP具有同时触发某些细胞信号传导途径的潜力，这可能导致由感染诱导的角膜和巩膜缺损的再生改善。在第一阶段SBIR工作中，我们的具体目标是（1）设计和制造原型iCAP器件，（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装置操作参数的试验范围，以及（3）证明iCAP可显著减少或消除细菌负荷，并协调感染诱导的角膜愈合。在相关的细菌性角膜炎的兔眼体内模型中的巩膜缺损。这些具体目标的成功完成应证明这种创新的新型微生物角膜炎治疗方法具有充分的可行性，并将使我们能够在未来的后续II期工作中执行更全面的技术开发和商业化目标。iCAP器械的最终商业可用性可能会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.