Photoreceptor Function in Retinopathy of Prematurity

描述(申请人提供)：早产儿视网膜病变(ROP)仍然是儿童双眼视力障碍的最常见原因。无论ROP是轻微的还是严重的，需要治疗，许多ROP患者视力不佳，并有可能日后出现眼睛和视力问题。我们发现，尽管视杆感光细胞功能的轻度缺陷持续存在，但在轻度、未经治疗的ROP中，受体后视网膜的功能可以恢复，但在重度、经治疗的ROP中则不能。在这个项目中，我们将使用互补视网膜电图(ERG)、心理物理和成像方法来研究光感受器和受体后视网膜及其血管系统。我们假设，受体后视网膜回路及其血管的重组是轻度ROP恢复的基础，而在更严重的ROP中，受损的神经血管可塑性阻止了重塑。作为推论，我们预测受体后视网膜对暗视和明视的视觉阈值有显著的限制。为了验证我们的假设，我们将研究早期婴儿期的ROP受试者，并纵向跟踪他们直到4岁；年龄在10到20岁的老年受试者将以横断面设计进行研究。视网膜功能评估包括视网膜视杆细胞和视锥细胞的ERG测量，以及术后4~10周和4年时视网膜受体和视网膜后功能的心理生理检查。在中间年龄，视网膜功能将使用暗适应阈值和背景适应的心理物理测试进行跟踪。该假说预测轻度ROP患者受体后功能恢复正常，但在重度ROP患者中则不然。视网膜血管系统的参数(曲度、直径、分布)将通过对所有受试者的眼底照片进行图像分析来量化，在老年受试者中将使用自适应光学(AO)成像。黄斑中心凹凹陷和视网膜层厚度将使用光学相干断层扫描(AO-OCT)进行评估，中心凹外视锥填充物的几何形状将使用扫描激光眼底镜(AO-SLO)进行研究。ERG反应、心理物理阈值和血管参数将被评估是否具有显著的相关性。用多焦ERG评估受体后功能，测试小的、离散的中央视网膜区域，将与老年受试者的视网膜层厚度、视锥填充物几何形状和视力进行比较。对婴幼儿的纵向研究将促进我们对ROP受体后视网膜动态重组的理解。对老年受试者的横断面研究将使我们能够进一步描述视网膜在限制视觉阈值方面的作用。该项目将为ROP的视觉发育调节机制提供新的见解，并通过定义视力缺陷的视网膜风险因素，为改善有ROP病史的儿童的临床管理奠定基础。 公共卫生相关性：早产儿视网膜病变(ROP)是全球儿童视力受损的主要原因；许多ROP患者面临终身视力低下的风险。我们使用视网膜功能和结构的测试来确定控制年轻ROP患者视觉发育的机制。我们的研究将带来对ROP疾病过程的新见解，从而改善ROP患者的管理和治疗。

DESCRIPTION (provided by applicant): Retinopathy of prematurity (ROP) remains the most frequent ocular cause of pediatric bilateral visual impairment. Whether ROP is mild or so severe that it requires treatment, many ROP patients suffer poor vision and risk of later eye and vision problems. We discovered that although mild deficits in rod photoreceptor function persist, function of the post-receptor retina recovers in mild, untreated ROP but not in severe, treated ROP. In this project, we will use complementary electroretinographic (ERG), psychophysical, and imaging methods to study the photoreceptors and post-receptor retina and its vasculature. We hypothesize that reorganization of post-receptor retinal circuitry and its vasculature is the basis for recovery in mild ROP and that in more severe ROP, compromised neurovascular plasticity precludes remodeling. As a corollary, we predict that the post-receptor retina places significant constraints on scotopic and photopic visual thresholds. To test our hypothesis, we will study ROP subjects in early infancy and follow them longitudinally to age 4 years; older subjects, age 10 to 20 years, will be studied in a cross-sectional design. Evaluation of retinal function will include ERG measures of rod and cone photoreceptor and post-receptor sensitivity and psycho-physical investigation of receptor and post-receptor function at 4 to 10 weeks and 4 years. At intervening ages, retinal function will be tracked using psychophysical tests of dark adapted thresholds and background adaptation. The hypothesis predicts normalization of post-receptor function in mild ROP but not in more severe ROP. Parameters of the retinal vasculature (tortuosity, diameter, distribution) will be quantified using image analysis of fundus photographs in all subjects, and in older subjects using adaptive optics (AO) imaging. The foveal pit and retinal layer thickness will be assessed using optical coherence tomography (AO-OCT), and extrafoveal cone packing geometry will be studied using scanning laser ophthalmoscopy (AO-SLO). ERG responses, psychophysical thresholds, and blood vessel parameters will be evaluated for significant relationships. Post-receptor function, assessed with the multifocal ERG, which tests small, discrete central retinal regions, will be compared to retinal layer thickness, cone packing geometry, and visual acuity in the older subjects. The longitudinal study of infants and young children will advance our understanding of the dynamic reorganization of the ROP post-receptor retina. The cross-sectional study of older subjects will allow us to further delineate the role of the retina in constraining visual thresholds. This project will provide new insights into mechanisms regulating visual development in ROP and, by defining retinal risk factors for visual deficits, lay the groundwork for improved clinical management of children with a history of ROP. PUBLIC HEALTH RELEVANCE: Retinopathy of prematurity (ROP) is a leading cause of visual impairment in children worldwide; many ROP patients are at risk for life-long poor vision. We use tests of retinal function and structure to identify mechanisms that control the visual development in young ROP patients. Our research will lead to new insights about the ROP disease process which will lead to improved management and treatment for ROP patients.