Structure function correlation of high resolution retinal imaging in early age-related macular degeneration and physiological aging

早期年龄相关性黄斑变性与生理衰老高分辨率视网膜成像的结构功能相关性

• 批准号: 531685551
• 负责人: Dr. Lukas Goerdt
• 金额: --
• 依托单位: Universitäts-Augenklinik Bonn
• 依托单位国家: 德国
• 项目类别: WBP Fellowship
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/531685551?language=en
• 关键词: Structure; function; correlation; resolution; retinal

Although age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and has long been a major focus of research in ophthalmology, its pathogenesis is yet to be fully understood. First subtle changes in the central retina usually develop after the age of 50. For the neovascular late disease stage (macular neovascularization, MNV) there is a successful therapy with the application of intravitreal anti-VEGF agents (vascular endothelial growth factor). For the dry late stage (geographic atrophy, GA) there are no therapeutic options so far. Therefore, the goal must be to distinguish physiologically aging eyes from those developing AMD at an early stage in order to provide them with possible preventive measures before one of the late stages develops. Currently, the so-called "center-surround model" of pathogenesis is being discussed. Here it is postulated that a central focus of the cone photoreceptors resilience, mediated by a concentration of Müller cells and xanthophyll macular pigment, is surrounded by a rod photoreceptor vulnerability, mediated by a lack of xanthophyll macular pigment and an increased occurrence of drusen, which limit the exchange of nutrients between retinal pigment epithelium and choriocapillaris. The aim of the present research project is to further validate this "center-surround model". Using data collected in the natural history study ALSTAR-2, modern high-resolution imaging (optical coherence tomography [OCT], fluorescence lifetime ophthalmoscopy [FLIO], macular pigment density measurements [MPOD]) and detailed assessments of retinal function (Rod mediated dark adaptation, RMDA) will be used to investigate to what extent physiologically aging eyes differ from AMD-developing eyes. In addition, questionnaires will be used to investigate whether and to what extent nutritional habits of the study participants affect xanthophyll levels measured in blood serum. The present research project can be divided into four distinct work packages: 1) Analysis of the influence of individual retinal thicknesses in the ETDRS grid region on the FLIO signal. 2) Analysis of the influence of individual retinal layer thicknesses in the area of the ETDRS grid on the MPOD signal. 3) Analysis of a possible correlation between FLIO and MPOD signal and RMDA values in the area of the test loci. 4) Analysis of the influence of study participants' nutritional habits on serum xanthophyll levels and MPOD measurements in the ETDRS grid area. If further validation of the center-surround model including the influence of serum xanthophyll levels on FLIO/MPOD signal and RMDA test values is successful and an association of dietary habits with xanthophyll levels and MPOD measurements is found, new behavioral recommendations for AMD prevention and reduction of progression of early-stage AMD patients will be developed.

尽管老年性黄斑变性(AMD)是发达国家导致失明的主要原因，也是眼科研究的重点，但其发病机制尚不完全清楚。首先，中央视网膜的细微变化通常发生在50岁之后。对于新生血管晚期疾病(黄斑新生血管，MNV)，有一种成功的治疗方法，即玻璃体内应用抗VEGF药物(血管内皮生长因子)。对于干燥的晚期(地理萎缩，GA)，到目前为止还没有治疗选择。因此，目标必须是区分生理性老化的眼睛和那些早期发展的AMD，以便在晚期发展之前为他们提供可能的预防措施。目前，所谓的“中心-环绕模型”的发病机制正在讨论中。这里假设视锥感光细胞弹性的中心焦点是由大量Müller细胞和叶黄素黄斑色素介导的，被视杆状光感受器脆弱性所包围，而视锥感光细胞黄斑色素的缺乏和视网膜色素上皮和脉络膜毛细血管之间营养物质交换的增加限制了视网膜色素上皮和脉络膜毛细血管之间的营养交换。本研究的目的是进一步验证这一“中心-环绕模型”。利用自然历史研究ALSTAR-2中收集的数据，将使用现代高分辨率成像(光学相干断层扫描[OCT]、荧光寿命眼底镜[Flio]、黄斑色素密度测量[MPOD])和视网膜功能详细评估(Rod介导的暗适应，RMDA)来调查生理老化的眼睛与AMD发展中的眼睛有何不同。此外，将使用问卷调查研究参与者的营养习惯是否以及在多大程度上影响血清中测量的叶黄素水平。目前的研究项目可以分为四个不同的工作包：1)分析ETDRS网格区个体视网膜厚度对Flio信号的影响。2)分析了ETDRS网格区视网膜各层厚度对MPOD信号的影响。3)分析了Flio和MPOD信号与测试基因座区域RMDA值之间的可能相关性。4)分析研究参与者的营养习惯对ETDRS格点区域血清叶黄素水平和MPOD测量的影响。如果中心-周围模型的进一步验证成功，包括血清叶黄素水平对Flio/MPOD信号和RMDA测试值的影响，并发现饮食习惯与叶黄素水平和MPOD测量相关联，将开发新的AMD预防和减缓早期AMD患者进展的行为建议。