Analyzing retinal microanatomy in retinopathy of prematurity to improve care

 描述(申请人提供)：早产儿视网膜病变(ROP)是一种神经视网膜及其血管系统的发育障碍，可能会影响脆弱的早产儿一生的视力。对患有ROP的婴儿进行临床护理可以降低失明的可能性，但视力异常是常见的，特别是在那些疾病严重到需要治疗的人中。由于目前还不能区分是否影响特定视网膜细胞和/或中枢神经系统(CNS)的疾病和/或发育不良导致视力丧失，特别是在其不那么严重的情况下，因此还没有策略来预防大多数接受ROP治疗的婴儿视力低于正常。早产儿早产的间隔时间 ROP在重症监护室(ICN)度过的风险是视网膜快速发育的时期。临床医生和研究人员不知道视网膜显微解剖如何反映局部、中枢神经系统和系统的发育和疾病过程。婴儿期视网膜的异常可能是以后视力问题和发育迟缓的早期预测指标。通过对早产儿视网膜亚结构、脑解剖、连通性和功能网络以及神经炎性生物标志物的研究，本研究将阐明局部视网膜解剖变化影响的途径，并可能预测后期视力和中枢神经系统功能异常。这项研究的结果将使我们能够：区分眼睛和非眼睛对视力损失的贡献，指导未来针对改善视网膜异常(如浮肿)的治疗；并确定哪些显微解剖视网膜生物标志物最能监测ROP的效果，以及系统治疗对眼睛和大脑的影响。与间接眼底镜或照相相比，床边的新型非接触式眼科成像将使直接远程医疗筛查ROP和多个托儿所的神经发育成为可能。我们的长期目标是通过客观的床边成像和分析来帮助改善早产儿的健康护理，这些成像和分析表征了视力低下、神经发育和ROP的早期关键指标。这将迅速转化为早期干预和改善未来的视力护理。这项研究的具体目标有三个：实施技术创新，以改进ICN中未服用镇静剂的婴儿的光学相干断层扫描(OCT)成像；区分预测视觉通路发育不良和神经发育不良的视网膜显微解剖元素，这些元素可能影响早产儿的视力；以及描绘早产儿OCT衍生视网膜显微解剖的哪些元素和区域(后部和外围)最好地告知我们ROP婴儿的疾病严重程度和视觉结局。除了为极早产儿(VPT)的后部和外周视网膜的床边分析提供突破性的方法外，这项研究还将为儿科眼科和远程医学界提供区分显微解剖标志物的方法，这些标志物可以预测婴儿存在视力异常、视觉通路损伤、功能发育不良和ROP(及其组合)的风险。这些生物标志物将有助于确定眼科和中枢神经系统治疗干预措施，并监测它们对视觉通路的影响，因此很可能与其他婴儿眼和脑疾病相关。

 DESCRIPTION (provided by applicant): Retinopathy of prematurity (ROP) is a disorder of development of the neural retina and its vasculature that may impact vision in vulnerable preterm neonates for a lifetime. Clinical care of infants with ROP decreases the likelihood of blindness, but abnormal vision is common, especially in those with disease severe enough to require treatment. Because it has not been possible to distinguish whether disease and/or maldevelopment that affects specific retinal cells and/or the central nervous system (CNS) cause the vision loss, especially when it is less severe, there has been no strategy to prevent subnormal acuity in the majority of infants treated for ROP. The interval that a preterm infant at risk for ROP spends in an intensive care nursery (ICN) is a time of rapid retinal development. Clinicians and researchers do not know how local, CNS and systemic development and disease processes are reflected in the retinal microanatomy. Abnormalities in the retina during infancy are likely early predictors of later vision problems and developmental delay. From study of preterm retinal substructures, brain anatomy, connectivity and functional networks and neuroinflammatory biomarkers this study will elucidate the pathway by which local retinal anatomic changes impact and may predict later subnormal vision and CNS function. The results of this research will enable us to: distinguish ocular from non-ocular contributions to vision loss guide future treatment directed to modify retinal anomalies such as edema; and determine which microanatomic retinal biomarkers are best to monitor effects of ROP, and effects of systemic therapies on the eye and brain. In contrast to indirect ophthalmoscopy or photography, novel non-contact ocular imaging at the bedside would enable direct telemedicine screening for ROP and for neural development in multiple nurseries. Our long-term goal is to help improve preterm infant health care via objective bedside imaging and analysis that characterizes early critical indicators of poor vision, neurological development and ROP. This will rapidly translate t early intervention and improved future vision care. Specific goals of this research are threefold: to implement technological innovations to improve optical coherence tomography (OCT) imaging in non-sedated infants in the ICN; to distinguish elements of retinal microanatomy which predict maldevelopment of visual pathway and poor neurodevelopment that may impact vision in preterm infants; and to delineate which elements and regions (posterior and peripheral) of preterm infant OCT-derived retinal microanatomy best inform us about severity of disease and visual outcomes in infants with ROP. In addition to providing a breakthrough method for bedside analysis of the very preterm (VPT) infant posterior and peripheral retina, this study will provide the pediatric ophthalmologic and telemedicine community with methods to distinguish microanatomic markers that predict infants at risk for abnormal vision, visual pathway injury, poor functional development and progression of ROP (and combinations thereof). These biomarkers will be useful for determining ophthalmic and CNS therapeutic interventions and monitoring their impact on the visual pathway and will thus likely cross over with relevance to other infant eye and brain disease.