Photoreceptor Function in Retinopathy of Prematurity

描述（由申请人提供）：早产儿视网膜病变（ROP）仍然是儿童双侧视力障碍最常见的眼部原因。无论ROP是轻微的还是严重到需要治疗的程度，许多ROP患者的视力都很差，并且有可能出现后来的眼睛和视力问题。我们发现，虽然轻微的视杆光感受器功能缺陷持续存在，但在轻度未治疗的ROP中，后受体视网膜功能恢复，而在严重的ROP中则没有。在本项目中，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后感受器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系统的重组是轻度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碍了重塑。因此，我们预测后受体视网膜对暗视和光视阈值有重要的限制。为了验证我们的假设，我们将研究婴儿期早期的ROP受试者，并纵向跟踪他们到4岁；年龄在10至20岁之间的老年受试者将采用横断面设计进行研究。视网膜功能的评估将包括视杆和视锥光感受器的ERG测量和受体后敏感性，以及4至10周和4年的受体和受体后功能的心理-生理调查。在中间年龄，将使用暗适应阈值和背景适应的心理物理测试来跟踪视网膜功能。该假说预测轻度ROP的受体后功能正常化，但在更严重的ROP中则不然。所有受试者的视网膜血管参数（扭曲度、直径、分布）将通过眼底照片的图像分析进行量化，老年受试者使用自适应光学（AO）成像。将使用光学相干断层扫描（AO-OCT）评估中央凹凹和视网膜层厚度，并使用扫描激光检眼镜（AO-SLO）研究中央凹外锥体填充几何形状。将评估ERG反应、心理物理阈值和血管参数之间的显著关系。接受后功能，用多焦点ERG（测试小的、离散的视网膜中央区域）评估，将与老年受试者的视网膜层厚度、视锥填充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后受体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绘视网膜在限制视觉阈值方面的作用。该项目将为ROP的视觉发育调控机制提供新的见解，并通过定义视觉缺陷的视网膜危险因素，为改善有ROP病史儿童的临床管理奠定基础。

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.