Retinal imaging in Alzheimer's and neurodegenerative diseases

Snyder, Peter J.; Alber, Jessica; Alt, Clemens; Bain, Lisa J.; Bouma, Brett E.; Bouwman, Femke H.; DeBuc, Delia Cabrera; Campbell, Melanie C. W.; Carrillo, María C.; Chew, Emily Y.; Cordeiro, M. Francesca; Dueñas, Michael R.; Fernández, Brian; Koronyo‐Hamaoui, Maya; Morgia, Chiara La; Carare, Roxana O.; Sadda, Srinivas R.; Wijngaarden, Peter van; Snyder, Heather M.

doi:10.1002/alz.12179

Cited by 127 publications

(118 citation statements)

References 70 publications

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“…The retina is an essential part of the CNS. Due to its transparent nature to light, it is possible to use less invasive and high-resolution imaging modalities to visualise the retina [26,27]. It is predominantly known for its involvement in converting light energy into electrical signals [28].…”

Section: Retinal Microgliamentioning

confidence: 99%

“…Frequently occurring symptoms of MS involves the ocular pathway such as RNFL thinning, optic neuritis (ON) characterised by inflammatory damage to the optic nerve and uveitis characterised by intraocular inflammation of the vitreous body, retina, and uveal tract [62][63][64][65][66]. It has also been reported that such retinal changes may occur before changes in the rest of the CNS in many neurodegenerative diseases, including MS [26]. These recent findings have led to much interest in retinal research.…”

Section: Multiple Sclerosismentioning

confidence: 99%

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Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Choi¹,

Guo²,

Cordeiro

2021

Cells

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Microglia are the resident immune cells of the central nervous system (CNS), including the retina. Similar to brain microglia, retinal microglia are responsible for retinal surveillance, rapidly responding to changes in the environment by altering morphotype and function. Microglia become activated in inflammatory responses in neurodegenerative diseases, including multiple sclerosis (MS). When activated by stress stimuli, retinal microglia change their morphology and activity, with either beneficial or harmful consequences. In this review, we describe characteristics of CNS microglia, including those in the retina, with a focus on their morphology, activation states and function in health, ageing, MS and other neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, glaucoma and retinitis pigmentosa, to highlight their activity in disease. We also discuss contradictory findings in the literature and the potential ways of reducing inconsistencies in future by using standardised methodology, e.g., automated algorithms, to enable a more comprehensive understanding of this exciting area of research.

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Section: Retinal Microgliamentioning

confidence: 99%

Section: Multiple Sclerosismentioning

confidence: 99%

Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Choi¹,

Guo²,

Cordeiro

2021

Cells

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“…Yet, imaging of the skull-shielded brain poses various limitations for widespread screening in the clinical setting. The retina is a central nervous system organ that exhibits many of the pathological hallmarks of AD (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) and is far more accessible for repeated and highresolution imaging (32)(33)(34)(35)(36)(37)(38)(39)(40). Dysfunctional pericytes in the blood-brain barrier (BBB) are signi cant contributors to the pathogenesis of vascular cognitive impairment, including cerebral small vessel and large vessel disease and AD (26, 41).…”

Section: Introductionmentioning

confidence: 99%

Integrated Retinal Amyloid Burden With Retinal Venular Tortuosity Predicts Verbal Memory Impairment

Dumitrascu

Rosenberry

Sherman

et al. 2021

Preprint

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INTRODUCTION: Retinal imaging is a non-invasive tool to study retinal vasculature and neurodegeneration. Patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD)-related cognitive disorder exhibit both retinal vascular abnormalities and intraretinal accumulation of amyloid beta-protein (Aβ) plaque. Curcumin-enhanced retinal fluorescence imaging (CRFI) was recently translated as a safe imaging tool for retinal Aβ plaque quantification, holding promise as an early-stage pathological biomarker of AD. In this exploratory study, we sought to determine whether retinal vascular features combined with retinal amyloid burden correlate with the neurocognitive status.METHODS: We used scanning laser ophthalmoscopy to assess quantitative CRFI in a cohort of patients with cognitive impairment that underwent standard neuropsychological testing. Retinal blood vessels were segmented in a predefined circumpapillary region of interest. For each centerline, vessel tortuosity index, vessel inflection index and branching angle was quantified. Additionally, we automatically quantified retinal amyloid count in the supero-temporal quadrant and its subregions: posterior pole, proximal mid-periphery, and distal mid-periphery. Investigators performing quantifications were blinded to the subjects’ clinical characteristics. Linear regression models were used to assess the correlations between retinal vascular and amyloid parameters and cognitive domain Z-scores.RESULTS: In this pilot study, 34 subjects underwent automated retinal amyloid imaging and 29 subjects (55% female, mean age 64±6 years) had the combined retinal amyloid and peripapillary vascular analysis. Eleven subjects had normal cognition, 15 MCI, 2 probable AD and 1 non-AD dementia. CRFI was increased in individuals with impaired versus normal cognitive function (p 0.0012). Venous VTI was the most significant vascular parameter that differ across levels of CDR. Branching angle correlated with amyloid count in the distal mid-periphery (p=0.03), whereas vessel inflexion index correlated with posterior pole amyloid count (p=0.02). The combined proximal mid-periphery amyloid count – venous tortuosity index was found to exhibit highly significant group differences between cognitively impaired and cognitively normal subjects (0.49 ± 1.1 vs 0.91 ± 1.4, p=0.006). The combined proximal mid-periphery amyloid-venous tortuosity index also correlated with verbal memory (Wechsler Memory Scale-IV; p=0.001) and cognitive-related quality of life (SF-36 mental component score Z-scores; p=0.039).CONCLUSION: Retinal venular tortuosity discriminates across cognitive scores and in combination with proximal mid-periphery amyloid count predicts verbal memory and cognitive-related quality-of-life. Future research is needed to confirm the clinical utility of this integrated retinal imaging-based methodology.

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“…However, the strong link between the eye and the central nervous system is supported by evidence that the ocular alterations existing in various neurodegenerative pathologies of the CNS and visual manifestations sometimes precede central symptoms. Moreover, the retina is a CNS compartment that can be easily analyzed with optical techniques, such as, for example, the optical coherence tomography (OCT), so retinal changes may reflect the pathological features in the brain early in the disease processes [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Ocular Neurodegenerative Diseases: Interconnection between Retina and Cortical Areas

Marchesi

Fahmideh

Boschi

et al. 2021

Cells

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The possible interconnection between the eye and central nervous system (CNS) has been a topic of discussion for several years just based on fact that the eye is properly considered an extension of the brain. Both organs consist of neurons and derived from a neural tube. The visual process involves photoreceptors that receive light stimulus from the external environment and send it to retinal ganglionic cells (RGC), one of the cell types of which the retina is composed. The retina, the internal visual membrane of the eye, processes the visual stimuli in electric stimuli to transfer it to the brain, through the optic nerve. Retinal chronic progressive neurodegeneration, which may occur among the elderly, can lead to different disorders of the eye such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Mainly in the elderly population, but also among younger people, such ocular pathologies are the cause of irreversible blindness or impaired, reduced vision. Typical neurodegenerative diseases of the CSN are a group of pathologies with common characteristics and etiology not fully understood; some risk factors have been identified, but they are not enough to justify all the cases observed. Furthermore, several studies have shown that also ocular disorders present characteristics of neurodegenerative diseases and, on the other hand, CNS pathologies, i.e., Alzheimer disease (AD) and Parkinson disease (PD), which are causes of morbidity and mortality worldwide, show peculiar alterations at the ocular level. The knowledge of possible correlations could help to understand the mechanisms of onset. Moreover, the underlying mechanisms of these heterogeneous disorders are still debated. This review discusses the characteristics of the ocular illnesses, focusing on the relationship between the eye and the brain. A better comprehension could help in future new therapies, thus reducing or avoiding loss of vision and improve quality of life.

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Retinal imaging in Alzheimer's and neurodegenerative diseases

Cited by 127 publications

References 70 publications

Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Integrated Retinal Amyloid Burden With Retinal Venular Tortuosity Predicts Verbal Memory Impairment

Ocular Neurodegenerative Diseases: Interconnection between Retina and Cortical Areas

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