Handheld Ocular Flare Meter Clinical Study

描述(申请人提供)：尽管美国约有300,000至600,000人患有活动性葡萄膜炎，但临床上还没有一种被临床接受的方法来对眼睛闪光进行定量评估，从而导致对葡萄膜炎的快速、非侵入性诊断。目前诊断葡萄膜炎的方法包括用裂隙灯显微镜和眼底镜彻底检查眼睛。在某些形式的葡萄膜炎患者中，较高水平的闪光尤其与视力不良有关，例如与幼年性关节炎相关的葡萄膜炎(Holland&Stiehm 2003)(Rosenberg等人)。2004年)。这些测试既是时间密集型的，又是很大程度上主观的(Kempen等人。2008年)。目前FDA批准的唯一能够提供葡萄膜炎程度客观评估的设备是KOVA激光耀斑测量仪(FM-600)；这是一种台式设备，不适合广泛现场使用，具有成本效益。为了满足这一重大的健康需求，ChromoLogic LLC(CL)将开发和验证一种手持式眼部闪光仪(OFAM)，这是一种非侵入性仪器平台，在不到1分钟的时间内就能诊断疾病和辐射导致的血眼屏障破坏。用早期原型获得的初步体外和中试临床数据已经证明了该技术的有效性。结果还显示，初始灵敏度远远超过商用台式KOVA产品(100倍)。在拟议项目的第一阶段，CL将进一步优化OFAM技术，并通过阶段性动物和临床研究展示其敏感性和特异性。来自阶段的结果将用于FDA的IDE申报。 与公共健康相关：哺乳动物的眼睛和大脑一样，被认为是免疫特权器官，因为它包含多种延缓炎症的机制。这是一种为了保持视力而发展起来的生物学上的需要。因此，眼睛的任何炎症，如葡萄膜炎，都会影响视力，有时还会永久损害视力。在任何给定的时间，美国大约有30万到60万人患有活动性葡萄膜炎。西方世界大约10%的视力障碍和美国高达15%的全盲病例可归因于葡萄膜炎。解决问题的关键 处理活动性葡萄膜炎，预防由此产生的不良影响是及时可操作的诊断。目前诊断葡萄膜炎的方法包括用裂隙灯显微镜和眼底镜对眼睛进行彻底检查，从而产生被称为眼部红斑的主观评分。在某些形式的葡萄膜炎患者中，尤其是高水平的耀斑与较差的视觉结果有关，例如与幼年性关节炎相关的葡萄膜炎。这些测试既耗费时间，又具有很大的主观性。目前唯一能够客观评估KOVA激光耀斑计(FM-600)葡萄膜炎程度的设备；这是一种既不划算也不敏感的台式设备 葡萄膜炎的早期。因此，这项有20多年历史的技术今天并没有被用于临床诊断。鉴于葡萄膜炎可能导致的有害后果的严重性和规模，以及缺乏客观方法来诊断病情和监测所用的任何治疗，迫切需要一种快速、便携和高度敏感的诊断解决方案。

DESCRIPTION (provided by applicant): Although there are ~300,000 to 600,000 individuals in the United States with active uveitis, there is no clinically accepted method for quantitative assessment of ocular flare that would result in rapid, non-invasive diagnosis of uveitis. Current methods of diagnosis for uveitis involve a thorough examination of the eye with a slit lamp microscope and ophthalmoscopy. Higher levels of flare in particular have been associated with poor visual outcomes in patients with certain forms of uveitis, such as uveitis associated with juvenile arthritis (Holland & Stiehm 2003)(Rosenberg et al. 2004). These tests are both time intensive and largely subjective (Kempen et al. 2008). The only FDA approved device that currently is able to provide an objective assessment of the degree of uveitis is the KOWA laser flare meter (FM-600); this is a bench top device and is not suitable for cost effective for widespread field use. To overcome this major health need, ChromoLogic LLC (CL), will develop and validate a handheld Ocular Flare meter (OFAM) - a non-invasive instrument platform that has shown promise in diagnosing disease and radiation induced blood eye barrier disruption in less than 1minute. Preliminary in vitro and pilot clinical data obtained with an early generation prototype has demonstrated the efficacy of the technology. The results also show initial sensitivities that far exceed (100X) the commercially available bench top KOWA product. During Phase I of the proposed project, CL will further optimize the OFAM technology and demonstrate its sensitivity and specificity through staged animal and clinical studies. The results from Phase will be used towards an FDA IDE filing. PUBLIC HEALTH RELEVANCE: The mammalian eye, like the brain, is considered an immunologically privileged organ because it includes multiple mechanisms that stave of inflammation. This is a biological necessity developed to preserve visual acuity. As a result, any inflammation to the eye, known as uveitis affects vision and sometimes, permanently damages it. At any given time, there are approximately 300,000 to 600,000 individuals in the United States that have active uveitis. Approximately 10% of visual handicaps in the western world and up to 15% of all cases of total blindness in the United States is attributed to uveitis. The key to managing active uveitis and preventing deleterious effects resulting form it is timely actionable diagnosis. Current methods of diagnosis for uveitis involve a thorough examination of the eye with a slit lamp microscope and ophthalmoscopy - resulting in a subjective score known as ocular flare. Higher levels of flare in particular have been associated with poor visual outcomes in patients with certain forms of uveitis, such as uveitis associated with juvenile arthritis. Thes tests are both time intensive and largely subjective. The only device that currently is able to provide an objective assessment of the degree of uveitis in the KOWA laser flare meter (FM-600); this is a bench top device that is neither cost effective nor has the sensitivity to diagnose early stages of uveitis. As a result, this 20+ year old technology is not being used for clinical diagnosis today. Given the severity and scale of deleterious outcomes that could result from uveitis and the lack of an objective method to diagnose the condition and monitor any therapies administered, there is an urgent need for a rapid, portable and highly sensitive diagnostic solution.