Bedside Optical Retinal Assessment of Hypoxic Ischemic Encephalopathy in Infants

项目摘要 在发达国家，儿童失明最常见的原因是皮质盲;窒息性损伤是 这是造成这种长期视力损害的众所周知的原因。缺氧缺血性脑病（HIE）也是 由严重的围产期窒息引起，长期结果包括运动、认知和视觉缺陷， 其中一些在婴儿早期可能不明显，所有这些都影响生活质量。临床医生必须 在出生后的最初几个小时内确定婴儿是否患有HIE，以便启动时间依赖性低温 治疗，第一线的干预，虽然即使与低温，死亡率和残疾率是 仍然很高。神经系统检查一直是诊断和随访评估的主要工具。在 出生后大约一周，使用脑磁共振成像（MRI）来量化脑损伤 并与检查一起用于预测神经学结果。发育预后试验 信息仍然是复杂和有限的，即使是轻度MRI结果的婴儿也有一系列结果， 在很多情况下很难预测。需要一个简单的床边测试来增加有意义的信息 关于这些婴儿的眼睛和大脑损伤。视网膜和视神经乳头（retina/ONH）是一个延伸， 位于间脑的中间，是进入视觉通路的入口，视觉通路占大脑的25%以上。内 在中枢神经系统中，视网膜/ONH是唯一适合于光学成像的结构， 亚细胞水平的光谱域光学相干断层扫描（SD-OCT）。填补床边测试的差距 本研究提出了一种新的非接触式床旁SD-OCT视网膜/ONH成像， 没有药理学扩张，以检测显微解剖结构中的异常，这些异常是： 窒息，由继发性再灌注损伤或神经炎症发展，或由逆行性 萎缩每种类型的损伤都是HIE严重程度和治疗反应的潜在有用指标。这 这项研究建立在对一小群患有SD-OCT的HIE婴儿进行这种眼睛成像的发现的基础上。 特征包括视网膜损伤。这些发现激发了这里提出的步骤，以进行前瞻性研究。 两个托儿所的HIE婴儿的成像，以测试视网膜/ONH的捕获和测量的假设， 异常是可实现的和可再现的，存在一系列异常的严重程度，并且这些 与正常人群不同，反映了MRI脑损伤评分，并随着时间的推移而变化。的 这项研究的结果将为临床医生和研究人员提供突破性的可重复方法， 标准化床旁成像和图像分析。通过区分基于SD-OCT的显微解剖成像 新生儿视网膜/ONH窒息性损伤的严重程度和持续时间的生物标志物，这项研究将改变未来 在HIE、窒息损伤和患有包括视网膜病在内的其他眼脑疾病的婴儿中的临床研究 早产、色素失禁等遗传性疾病以及寨卡相关的眼和脑损伤。

PROJECT SUMMARY The most common cause of childhood blindness in the developed world is cortical blindness; asphyxial injury is a well-known cause of such long-term visual impairment. Hypoxic ischemic encephalopathy (HIE) is also caused by severe perinatal asphyxia, and long-term outcomes include motor, cognitive, and visual deficits, some of which may not be apparent in early infancy and all of which impact quality of life. Clinicians must determine within the first hours of life whether an infant has HIE in order to initiate time-dependent hypothermia treatment, the first line of intervention, although even with hypothermia, mortality rates and disability rates are still high. Neurological examinations have been the primary tool for diagnosis and follow up assessment. At approximately one week after birth, brain magnetic resonance imaging (MRI) is used to quantify brain injury and together with examinations is used to predict neurological outcomes. Tests for developmental prognostic information remain complex and limited, and even infants with mild MRI findings have a range of outcomes that are difficult to predict in many cases. There is a need for a simple bedside test to add meaningful information regarding eye and brain injury in these infants. The retina and optic nerve head (retina/ONH) are an extension of the diencephalon and are the entry into the visual pathway, which comprises over 25% of the brain. Within the central nervous system, the retina/ONH are the only structures amenable to optical imaging at the subcellular level with spectral domain optical coherence tomography (SD-OCT). To fill the gap in bedside tests of early asphyxial injury, this study proposes novel non-contact, bedside SD-OCT imaging of retina/ONH without pharmacologic dilation, to detect abnormalities in microanatomy that are either: a direct result of asphyxia, that develop from secondary reperfusion injury or neuroinflammation, or that develop from retrograde atrophy. Each type of injury is a potentially useful indicator of HIE severity and treatment response. This research builds upon findings from such eye imaging in a very small group of HIE infants in whom SD-OCT features included retinal injury. Those findings motivate the steps proposed here, to perform prospective imaging of HIE infants in two nurseries to test the hypotheses that capture and measurement of retinal/ONH abnormalities are achievable and reproducible, that there is a range of severity of abnormalities and that these are distinct from the normal population, are reflective of MRI brain injury scores, and change over time. The results of this study will provide clinicians and researchers with breakthrough reproducible methods for standardized bedside imaging and image analyses. By distinguishing SD-OCT-based, micro-anatomic imaging biomarkers for severity and duration of newborn retinal/ONH asphyxial injury, this study will transform future clinical research in HIE, asphyxia injury and in infants with other eye and brain diseases including retinopathy of prematurity, genetic diseases such as incontinentia pigmenti, and Zika-associated eye and brain injury.