Endotying neurodegeneration through the eye using multimodal retinal imaging

神经退行性疾病影响着全世界数百万人，是一项全球公共卫生挑战。当大脑或周围神经系统中的神经细胞随着时间的推移失去功能并最终死亡时，就会发生这种情况。虽然目前还没有治愈方法，但早期发现提供了早期治疗的机会，可能有助于预防或减缓疾病进展，缓解症状，提高患者的生活质量。然而，准确的诊断可能具有挑战性。临床医生通过对患者进行长期检查来阐明体征和症状，通常会得到来自复杂和侵入性检查的生物标志物数据的支持，如MRI和PET成像以及脑脊液的生化分析。临床需要快速、侵入性小、患者更能耐受、更便宜、更准确的新检测和生物标志物。此外，在新疗法的试验中，人们高度寻求能够预测进展或作为结果测量的生物标志物。视网膜是人类神经系统的一个可接近的部分在那里我们可以研究神经细胞和小血管。由于视网膜和大脑在细胞和血管的组成和结构以及它们对损伤的炎症和免疫反应方面的相似性，加上在微米水平上成像的能力，意味着眼睛为神经变性和神经血管功能障碍提供了一个独特的“窗口”。应用于从爱丁堡患者收集的交联数据集，已经发现了影响大脑的疾病（如多发性硬化症、运动神经元疾病和痴呆症）的特征或表型的证据[3,4]。由我们的行业合作伙伴海德堡工程公司制造的SPECTRALIS平台，在一个设备上具有3种类型或模式的视网膜成像：扫描激光眼科检查（SLO），捕捉视网膜内表面的视图，包括视神经头、黄斑和小血管；光学相干断层扫描（OCT）用于视网膜和脉络膜的横断成像；oct血管造影（OCTA）成像最小的毛细血管网络。结合这些输出将使视网膜和周围神经组织的血管系统的详细特征，并进一步研究神经变性和神经血管功能障碍。通过眼睛产生新的见解将有助于更好地理解、区分和监测脑部疾病，并最终开发新的治疗靶点。目的探讨多模态视网膜成像和分析作为神经变性内分型的手段。确定从影像学中获得的候选生物标志物用于前瞻性临床应用。展示视网膜成像在神经学诊断、预后和监测中的应用。要检验的具体假设是：患有不同情况或神经退行性疾病亚型的人在视网膜测量方面会表现出显著差异。视网膜测量将与其他临床测试和脑成像中发现的异常相关联。视网膜的差异将在横断面和纵向测量上得到证明。视网膜测量可以预测患者的预后和/或病情恶化。神经退行性疾病的生物标志物。中华医学杂志；2011;27(6):954-963.2。伦敦A， Benhar I, Schwartz M.视网膜作为大脑的窗口——从眼睛研究到中枢神经系统疾病。中华神经科杂志，2013;9(1):44-53.3。小卡梅隆（2018）。眼作为大脑的窗口：研究视网膜成像衍生生物标志物在神经退行性疾病表型中的临床应用。博士论文，爱丁堡大学，爱丁堡，英国皮尔逊TMC（2019）。多模态视网膜扫描在神经退行性疾病诊断和治疗中的生物标志物发现。博士论文，爱丁堡大学，爱丁堡，英国

Neurodegenerative diseases affect millions of people worldwide and are a global public health challenge. They occur when nerve cells in the brain or peripheral nervous system lose function over time and ultimately die. While no cures currently exist, early detection provides a chance for earlier treatment that may help to prevent or slow disease progression with symptomatic relief to enhance patients' quality of life. However, accurate diagnosis can be challenging. A clinician examining a person to elucidate signs and symptoms over time is usually supported by biomarker data from complex and invasive tests such as MRI and PET imaging and biochemical analysis of cerebrospinal fluid. There is a clinical need for new tests and biomarkers that are quick, less invasive, better tolerated by patients, less expensive, and more accurate [1]. In addition, biomarkers that can predict progression or act as outcome measures in trials of new therapeutics are highly sought.The retina as an accessible part of the human nervous system where we can study nerve cells and small blood vessels [2]. With similarities between the retina and the brain in the composition and structure of cells and vessels and their inflammatory and immunologic reactions to insults combined with the capability to image at a micron level means the eye provides a unique "window" to neurodegeneration and neurovascular dysfunction. Applied to cross-linked datasets collected from patients in Edinburgh has already uncovered evidence of signatures or phenotypes in the eye of diseases affecting the brain such as multiple sclerosis, motor neuron disease, and dementias [3, 4].The SPECTRALIS platform manufactured by our industry partner, Heidelberg Engineering, features 3 types or modes of retinal imaging in one device: Scanning Laser Ophthalmoscopy (SLO) to capture views of the interior surface of the retina featuring the optic nerve head, macula and small blood vessels; Optical coherence tomography (OCT) for cross-sectional imaging of the retina and choroid; OCT-Angiography (OCTA) to image the smallest capillary-level vessel networks. Combining these outputs will enable a detailed characterisation of the vascular systems of the retina and surrounding nerve tissues and further the study of neurodegeneration and neurovascular dysfunction. Generating new insights through the eye will help develop a better understanding, differentiating and monitoring of brain disease, and eventually the development of new therapeutic targets.AimsInvestigate multimodal retinal imaging and analysis as a means of endotyping neurodegeneration.Identify candidate biomarkers derived from imaging for prospective clinical use.Demonstrate the utility of imaging the retina for neurology in diagnosis, prognosis, and monitoring.The specific hypotheses to be examined are:People with different conditions or subtypes of neurodegenerative disease will show significant differences in retinal measures.Retinal measures will correlate with abnormalities found on other clinical tests and brain imaging.Differences in the retina will be evidenced on both cross-sectional and longitudinal measures.Retinal measures will predict patient outcome and/or deterioration.References1. Hansson O. Biomarkers for neurodegenerative diseases. Nat Med. 2021 Jun;27(6):954-963.2. London A, Benhar I, Schwartz M. The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol. 2013 Jan;9(1):44-53.3. Cameron JR (2018). The Eye as a Window to the Brain: investigating the clinical utility of retinal imaging derived biomarkers in the phenotyping of neurodegenerative disease. PhD Thesis, University of Edinburgh, Edinburgh, UK4. Pearson TMC (2019). Multi-modal retinal scanning for diagnostic and therapeutic biomarker discovery in neurodegenerative disease. PhD Thesis, University of Edinburgh, Edinburgh, UK