Yi-Jun Ge1, Wei Xu1, Ya-Nan Ou1, Yi Qu1, Ya-Hui Ma1, Yu-Yuan Huang2, Xue-Ning Shen2, Shi-Dong Chen2, Lan Tan3, Qian-Hua Zhao4, Jin-Tai Yu5. 1. Department of Neurology, Qingdao Municipal Hospital, Qingdao University, China. 2. Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. 3. Department of Neurology, Qingdao Municipal Hospital, Qingdao University, China. Electronic address: dr.tanlan@163.com. 4. Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: qianhuazhao@fudan.edu.cn. 5. Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: jintai_yu@fudan.edu.cn.
Abstract
BACKGROUND: Retinal changes may reflect the pathophysiological processes in the central nervous system and can be assessed by imaging modalities non-invasively. We aim to localize candidate retinal biomarkers in Alzheimer's disease (AD), mild cognitive impairment (MCI), and preclinical AD. METHODS: We systematically searched PubMed, EMBASE, Scopus, and Web of Science from inception to January 2021 for observational studies that investigated retinal imaging and electrophysiological markers in AD, MCI, and preclinical AD. Between-groups standardized mean differences (SMDs) with 95% confidence intervals were computed using random-effects models. RESULTS: Of 19,727 citations identified, 126 articles were eligible for inclusion. Compared with healthy controls, the thickness of peripapillary retinal nerve fiber layer (pRNFL; SMD = -0.723, p < 0.001), total macular (SMD = -0.612, p < 0.001), and subfoveal choroid (SMD = -0.888, p < 0.001) were significantly reduced in patients with AD. Compared with healthy controls, patients with MCI also had lower thickness of pRNFL (SMD = -0.324, p < 0.001), total macular (SMD = -0.302, p < 0.001), and subfoveal choroid (SMD = -0.462, p = 0.020). Other candidate biomarkers included the optic nerve head morphology, retinal amyloid deposition, microvascular morphology and densities, blood flow, and electrophysiological markers. CONCLUSIONS: Retinal structural, vascular, and electrophysiological biomarkers hold great potential for the diagnosis, prognosis and risk assessment of AD and MCI. These biomarkers warrant further development in the future, especially in diagnostic test accuracy and longitudinal studies.
BACKGROUND: Retinal changes may reflect the pathophysiological processes in the central nervous system and can be assessed by imaging modalities non-invasively. We aim to localize candidate retinal biomarkers in Alzheimer's disease (AD), mild cognitive impairment (MCI), and preclinical AD. METHODS: We systematically searched PubMed, EMBASE, Scopus, and Web of Science from inception to January 2021 for observational studies that investigated retinal imaging and electrophysiological markers in AD, MCI, and preclinical AD. Between-groups standardized mean differences (SMDs) with 95% confidence intervals were computed using random-effects models. RESULTS: Of 19,727 citations identified, 126 articles were eligible for inclusion. Compared with healthy controls, the thickness of peripapillary retinal nerve fiber layer (pRNFL; SMD = -0.723, p < 0.001), total macular (SMD = -0.612, p < 0.001), and subfoveal choroid (SMD = -0.888, p < 0.001) were significantly reduced in patients with AD. Compared with healthy controls, patients with MCI also had lower thickness of pRNFL (SMD = -0.324, p < 0.001), total macular (SMD = -0.302, p < 0.001), and subfoveal choroid (SMD = -0.462, p = 0.020). Other candidate biomarkers included the optic nerve head morphology, retinal amyloid deposition, microvascular morphology and densities, blood flow, and electrophysiological markers. CONCLUSIONS: Retinal structural, vascular, and electrophysiological biomarkers hold great potential for the diagnosis, prognosis and risk assessment of AD and MCI. These biomarkers warrant further development in the future, especially in diagnostic test accuracy and longitudinal studies.