Retinal thinning and correlation with functional disability in patients with Parkinson's disease

Satué, María; Seral, M; Otı́n, Santos; Alarcia, Raquel; Herrero, Raquel; Bambo, M; Fuertes, M. I.; Júlvez, Luis Pablo; García‐Martín, Elena

doi:10.1136/bjophthalmol-2013-304152

Cited by 108 publications

(92 citation statements)

References 24 publications

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“…Furthermore, this protocol may serve to evaluate retinal microglia/peripheral monocyte changes resulting from chronic CNS pathologies, such as Alzheimer’s, Parkinson’s and multiple sclerosis, given that the retina and optic nerve are targeted for neurodegeneration in these diseases 51–56 . In line with this, the use of live detection of retina and ONH pathology for early Alzheimer’s disease management is under intense study 54,57,58 .…”

Section: Discussionmentioning

confidence: 96%

<em>In Vivo </em>Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma

Bosco

Romero

Ambati

et al. 2015

JoVE

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SHORT ABSTRACT Microglia activation and microgliosis are key responses to chronic neurodegeneration. Here, we present methods for in vivo, long-term visualization of retinal CX3CR1-GFP+ microglial cells by confocal ophthalmoscopy, and for threshold and morphometric analyses to identify and quantify their activation. We monitor microglial changes during early stages of age-related glaucoma. LONG ABSTRACT Microglia, which are CNS-resident neuroimmune cells, transform their morphology and size in response to CNS damage, switching to an activated state with distinct functions and gene expression profiles. The roles of microglial activation in health, injury and disease remain incompletely understood due to their dynamic and complex regulation in response to changes in their microenvironment. Thus, it is critical to non-invasively monitor and analyze changes in microglial activation over time in the intact organism. In vivo studies of microglial activation have been delayed by technical limitations to tracking microglial behavior without altering the CNS environment. This has been particularly challenging during chronic neurodegeneration, where long-term changes must be tracked. The retina, a CNS organ amenable to non-invasive live imaging, offers a powerful system to visualize and characterize the dynamics of microglia activation during chronic disorders. This protocol outlines methods for long-term, in vivo imaging of retinal microglia, using confocal ophthalmoscopy (cSLO) and CX3CR1-GFPGFP/+ reporter mice, to visualize microglia with cellular resolution. Also, we describe methods to quantify monthly changes in cell activation and density in large cell subsets (200–300 cells per retina). We confirm the use of somal area as a useful metric for live tracking of microglial activation in the retina by applying automated threshold-based morphometric analysis of in vivo images. We use these live image acquisition and analyses strategies to monitor the dynamic changes in microglial activation and microgliosis during early stages of retinal neurodegeneration in a mouse model of chronic glaucoma. This approach should be useful to investigate the contributions of microglia to neuronal and axonal decline in chronic CNS disorders that affect the retina and optic nerve.

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Section: Discussionmentioning

confidence: 96%

<em>In Vivo </em>Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma

Bosco

Romero

Ambati

et al. 2015

JoVE

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“…Recent studies demonstrate that both retinal function and morphology in patients with Parkinson’s disease are significant predictors of disease severity and quality of life [49–53]. Changes in the retinal nerve fiber layer measured by OCT have been reported in patients with Alzheimer’s Disease [54], and measurements of the choroid (the vascular rich layer of the eye deep to the retina) have shown significant choroidal thinning in AD patients as well [55].…”

Section: Discussionmentioning

confidence: 99%

Changes in Retinal Function and Morphology Are Early Clinical Signs of Disease in Cattle with Bovine Spongiform Encephalopathy

et al. 2015

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Bovine spongiform encephalopathy (BSE) belongs to a group of fatal, transmissible protein misfolding diseases known as transmissible spongiform encephalopathies (TSEs). All TSEs are caused by accumulation of misfolded prion protein (PrPSc) throughout the central nervous system (CNS), which results in neuronal loss and ultimately death. Like other protein misfolding diseases including Parkinson’s disease and Alzheimer’s disease, TSEs are generally not diagnosed until the onset of disease after the appearance of unequivocal clinical signs. As such, identification of the earliest clinical signs of disease may facilitate diagnosis. The retina is the most accessible part of the central nervous system, and retinal pathology in TSE affected animals has been previously reported. Here we describe antemortem changes in retinal function and morphology that are detectable in BSE inoculated animals several months (up to 11 months) prior to the appearance of any other signs of clinical disease. We also demonstrate that differences in the severity of these clinical signs reflect the amount of PrPSc accumulation in the retina and the resulting inflammatory response of the tissue. These results are the earliest reported clinical signs associated with TSE infection and provide a basis for understanding the pathology and evaluating therapeutic interventions.

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“…Altintaş et al demonstrated a relation between PD severity and alterations in foveal thickness using time-domain OCT [54]. An association between disease severity as measured by the Hoehn Yahr scale and macular thickness was also found using SD-OCT [57, 63]. Disease severity based on the commonly used Unified Parkinson's Disease Rating Scale III (UPDRS III) and quality of life (based on the Schwab England scale) is also correlated with macular measurements, especially temporal and inferior sectors [57, 63].…”

Section: Parkinson Diseasementioning

confidence: 99%

Optical Coherence Tomography as a Biomarker for Diagnosis, Progression, and Prognosis of Neurodegenerative Diseases

Satué

Obís

Rodrigo

et al. 2016

Journal of Ophthalmology

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Neurodegenerative diseases present a current challenge for accurate diagnosis and for providing precise prognostic information. Developing imaging biomarkers for multiple sclerosis (MS), Parkinson disease (PD), and Alzheimer's disease (AD) will improve the clinical management of these patients and may be useful for monitoring treatment effectiveness. Recent research using optical coherence tomography (OCT) has demonstrated that parameters provided by this technology may be used as potential biomarkers for MS, PD, and AD. Retinal thinning has been observed in these patients and new segmentation software for the analysis of the different retinal layers may provide accurate information on disease progression and prognosis. In this review we analyze the application of retinal evaluation using OCT technology to provide better understanding of the possible role of the retinal layers thickness as biomarker for the detection of these neurodegenerative pathologies. Current OCT analysis of the retinal nerve fiber layer and, specially, the ganglion cell layer thickness may be considered as a good biomarker for disease diagnosis, severity, and progression.

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Retinal thinning and correlation with functional disability in patients with Parkinson's disease

Abstract: The neurodegeneration caused by PD can be detected using Fourier domain OCT. RNFL and macular thicknesses correlate with PD severity.

Cited by 108 publications

References 24 publications

<em>In Vivo </em>Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma

<em>In Vivo </em>Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma

Changes in Retinal Function and Morphology Are Early Clinical Signs of Disease in Cattle with Bovine Spongiform Encephalopathy

Optical Coherence Tomography as a Biomarker for Diagnosis, Progression, and Prognosis of Neurodegenerative Diseases

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