Quantitative Fundus Autofluorescence in Retinal Disorders

视网膜疾病中的定量眼底自发荧光

• 批准号: 8619402
• 负责人: Janet Ruthe Sparrow
• 金额: $ 46.97万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8619402
• 关键词: Abbreviations; Address; Affect; Age; Age related macular degeneration; Alleles; Biological; Carrier State; Cells; Chemicals; Choroidal Neovascularization; Clinical; Complement Factor H; Complex; Complex Mixtures; Confidence Intervals; Data; Deposition; Diagnosis; Disease; Disease Progression; Electroretinography; Epithelial; Ethnic Origin; Etiology; Exhibits; Eye; Flecks; Fundus; Gender; Genetic; Genotype; Gray unit of radiation dose; Image; Individual; Influentials; Investigation; Lasers; Legal Blindness; Light; Link; Lipofuscin; Longitudinal Studies; Measurement; Measures; Membrane; Methods; Monitor; Mutation; Normal Range; Nuclear; Omi serine protease; Ophthalmoscopy; Optical Coherence Tomography; Optics; Outcome; Participant; Pathogenesis; Patients; Pattern; Phagocytosis; Phenotype; Photoreceptors; Physics; Pigments; Positioning Attribute; Predisposition; Process; Research Personnel; Retina; Retinal; Retinal Degeneration; Retinal Diseases; Retinal Pigments; Retinaldehyde; Retinitis; Retinitis Pigmentosa; Scanning; Single Nucleotide Polymorphism; Sparrows; Stargardt' s disease; Structure of retinal pigment epithelium; Susceptibility Gene; Testing; Therapeutic; Variant; Work; aged; base; clinical phenotype; cohort; early onset; fluorophore; follow-up; geographic atrophy; human disease; macular dystrophy; pattern dystrophies; peripherin; public health relevance; risk variant

DESCRIPTION (provided by applicant): The inherent autofluorescence (AF) of the fundus originates from RPE lipofuscin. While RPE lipofuscin is amassed even in healthy eyes, homozygous mutations in ABCA4 are well known to confer accelerated formation of these fluorophores. Moreover, imaging of fundus AF by confocal scanning laser ophthalmoscopy (cSLO) has shown that the patterns and intensities of AF deviate from normal in several retinal disorders. Thus we aim to demonstrate that a standardized approach to quantifying fundus AF (qAF) can assist in the diagnosis of retinal disease, in the monitoring of disease progression and in the assessment of therapeutic outcomes. To enable this investigation we have gathered normative qAF data from a large number of participants with healthy eye status (aged 6-60) so as to establish ranges of qAF values with respect to age, gender and ethnicity. Going forward we will use these normal values to examine for genotype/phenotype correlations between specific ABCA4 alleles and fundus AF levels (qAF) in patients diagnosed with ABCA4- associated disease (Aim 1.1). In longitudinal studies we will measure changes in qAF values after 1 and 2 year follow-up of ABCA4-affected individuals (Aim 1.2). We will determine whether the carrier state (heterozygous) of ABCA4 is associated with elevated RPE lipofuscin, the latter being measured as qAF and compared to age-matched normals (Aim 1.3). We will also investigate the cellular basis of retinal flecks (Aim 1.4). In Aim 2, we will determine whether the quantification of fundus SW-AF can aid in differentiating between pattern dystrophy (PD) associated with PRPH2/RDS mutations versus similar phenotypes observed with ABCA4 variants (Aim 2.1). We will also compare qAF values in individuals presenting with bull's eye macular dystrophy that is of ABCA4- versus non-ABCA4 origin (Aim 2.2). In patients with RP, we will measure qAF over the autofluorescent rings that are often a feature of this disorder. qAF Intensities inside, within and outside the rings will be compared to levels in our normal controls so as to further the use of fundus AF imaging to monitor disease progression in RP. In Aim 4, we will determine whether elevated fundus AF is a factor influencing the onset and progression of AMD when controlling for specific CFH and ARMS2 alleles. In summary, the studies proposed in this application will examine the contribution that the lipofuscin of retina makes to the onset and progression of several retinal diseases and will demonstrate that quantitation of fundus AF facilitates the diagnosis and monitoring of some retinal disorders.

描述(申请人提供)：眼底固有的自体荧光(AF)来源于RPE脂褐素。虽然RPE脂褐素即使在健康的眼睛中也会积聚，但众所周知，ABCA4的纯合子突变可以加速这些荧光团的形成。此外，共焦扫描激光眼底镜(CSLO)对眼底房颤的成像显示，在一些视网膜疾病中，房颤的模式和强度偏离了正常。因此，我们的目的是证明一种量化眼底房颤(QAF)的标准化方法可以帮助诊断视网膜疾病、监测疾病进展和评估治疗结果。为了使这项调查成为可能，我们收集了大量具有健康眼睛状况的参与者(6-60岁)的标准化QAF值，以建立与年龄、性别和种族相关的QAF值范围。展望未来，我们将使用这些正常值来检查诊断为ABCA4相关疾病的患者中特定ABCA4等位基因与眼底房颤水平(QAF)之间的基因型/表型相关性(AIM 1.1)。在纵向研究中，我们将测量受ABCA4影响的个体在1年和2年后QAF值的变化(目标1.2)。我们将确定ABCA4的携带者状态(杂合子)是否与RPE脂褐素升高有关，后者被测量为QAF，并与年龄匹配的正常人进行比较(目标1.3)。我们还将调查视网膜斑点的细胞学基础(目标1.4)。在目标2中，我们将确定是否 眼底Sw-AF的定量有助于区分与PRPH2/RDS突变相关的模式营养不良(PD)和ABCA4变异所观察到的类似表型(AIM 2.1)。我们还将比较患有ABCA4起源和非ABCA4起源的牛眼黄斑营养不良患者的QAF值(目标2.2)。在RP患者中，我们将测量自体荧光环上的QAF，这通常是这种疾病的一个特征。环内、环内和环外的QAF强度将与我们正常对照的水平进行比较，以便进一步使用眼底AF成像来监测RP的疾病进展。在目标4中，我们将在控制特定的CFH和ARMS2等位基因的情况下，确定眼底房颤升高是否是影响AMD发生和发展的因素。总之，本申请中提出的研究将检验视网膜脂褐素在几种视网膜疾病的发生和发展中的作用，并将证明眼底房颤的定量有助于某些视网膜疾病的诊断和监测。