The Impact of Non-Exudative Type 1 Macular Neovascularization (MNV) on Age-related Macular Degeneration (AMD) Progression

非渗出性 1 型黄斑新生血管 (MNV) 对年龄相关性黄斑变性 (AMD) 进展的影响

• 批准号: 10693953
• 负责人: Monika Fleckenstein
• 金额: $ 38.5万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10693953
• 关键词: Age related macular degeneration; Angiography; Area; Artificial Intelligence; Biological; Biological Markers; Biological Products; Blindness; Clinical; Clinical Research; Consumption; Data; Data Set; Development; Dimensions; Disease Progression; Event; Excision; Exhibits; Exudate; Exudative age-related macular degeneration; Eye; Fibrosis; Fundus; Future; Goals; Intervention; Letters; Membrane; Morphology; Non-Invasive Detection; Nonexudative age-related macular degeneration; Optical Coherence Tomography; Pathologist; Patients; Perimetry; Photoreceptors; Procedures; Process; Prognosis; Property; Protocols documentation; Research Personnel; Research Project Grants; Resolution; Retina; Role; Structure; Structure of retinal pigment epithelium; Testing; Therapeutic; Thinking; Time; Tissues; Vascular Endothelial Growth Factors; Vision; Visualization; cohort; data integration; improved; in vivo; macula; neovascular; neovascularization; novel therapeutic intervention; personalized medicine; photoreceptor degeneration; predictive modeling; preservation; prevent; professor; prospective; protective effect; response; retinal imaging; supervised learning

PROJECT SUMMARY Age-related macular degeneration (AMD) is the leading cause of severe vision loss in the developed world. AMD is characterized by progressive degeneration of photoreceptors and the retinal pigment epithelium (RPE) that may be accompanied by the development of macular neovascularization (MNV). MNV gets clinically apparent when these new vessels become ‘exudative’. This exudative stage of ‘neovascular’ AMD can be treated by application of biologics that inhibit vascular endothelial growth factor. Without treatment, exudative MNV typically results in extensive fibrosis with severe central vision loss. Interestingly, there is a growing body of evidence that photoreceptor and RPE degeneration is slowed down in eyes exhibiting ‘non-exudative type 1 MNV’ that is located in the sub-RPE space. However, the proof of a direct protective effect of this specific MNV sub-type on visual function in AMD is lacking. The proposed project aims to demonstrate (1) relative preservation of retinal function along with (2) preserved structure in the immediate vicinity of type 1 MNV, whereas progressive loss of sensitivity and degeneration occurs in the surrounding tissue. This will be approached by the application of in vivo high-resolution retinal imaging combined with spatially- resolved testing of retinal sensitivity by fundus-controlled perimetry. Furthermore, given the need to minimize the burden of laborious functional testing on patients and investigators in future studies in AMD, (3) artificial intelligence will be applied in order to infer retinal function from high-resolution retinal imaging. Aim is to identify a minimum set of clinical procedures that still allows estimation of spatially-resolved retinal sensitivity and that may be implemented in future study protocols. This research project challenges the current concept of AMD. Substantial evidence for a protective potential of type 1 MNV would support the view that MNV development is actually an intrinsic ‘rescue mechanism’. This project will provide essential information to interpret current treatment approaches in AMD and would also provide a rationale for controlled MNV induction as therapeutic strategy to prevent vision loss in AMD.

项目摘要 视网膜相关性黄斑变性（AMD）是发达国家严重视力丧失的主要原因。AMD 特征在于光感受器和视网膜色素上皮（RPE）的进行性变性， 可能伴随着黄斑新生血管（MNV）的发展。MNV在临床上很明显 当这些新血管变成“渗出性”时。这种渗出性阶段的“新生血管性”AMD可以通过以下方法治疗： 抑制血管内皮生长因子的生物制剂的应用。如果不治疗，渗出性MNV通常 导致广泛的纤维化和严重的中心视力丧失。 有趣的是，有越来越多的证据表明，光感受器和RPE的变性是减缓， 眼睛表现出位于RPE下空间的“非渗出性1型MNV”。然而，直接证明 缺乏这种特定MNV亚型对AMD中视觉功能的保护作用。拟议项目的目标 为了证明（1）视网膜功能的相对保留沿着（2）在即刻中保留的结构 在1型MNV附近，敏感性逐渐丧失和变性发生在周围组织中。 这将通过应用体内高分辨率视网膜成像结合空间成像来实现。 通过眼底控制视野检查法对视网膜敏感性进行分辨测试。此外，鉴于需要尽量减少 在未来的AMD研究中对患者和研究者进行费力的功能测试的负担，（3）人工 智能将被用于从高分辨率视网膜成像推断视网膜功能。目标是查明 一组最少的临床程序，仍然允许估计空间分辨视网膜灵敏度， 可以在未来的研究方案中实施。 该研究项目挑战了AMD当前的概念。有充分证据表明， 1型MNV将支持这样的观点，即MNV的发展实际上是一种内在的“拯救机制”。这 该项目将提供必要的信息，以解释目前的治疗方法在AMD，也将 为控制MNV诱导作为预防AMD视力丧失的治疗策略提供了理论基础。