Inner retinal thinning as a biomarker for cognitive impairment in de novo Parkinson’s disease

Sung, Mi Sun; Choi, Seong-Min; Kim, Jong-Hwa; Ha, Jun Young; Kim, Byeong‐Chae; Heo, Hwan; Park, Sang Woo

doi:10.1038/s41598-019-48388-7

Cited by 33 publications

(52 citation statements)

References 46 publications

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“…However, the majority of previous OCT studies in PD failed to demonstrate statistically significant results or yielded contradictory findings regarding the link between retinal atrophy and motor disability or disease duration 22 . Given that macular GCIPL atrophy has been reported in de novo PD patients 23 and in prodromal phases of LBD 24 and the lack of its correlation with disease duration or motor manifestations, it may suggest that retinal injury is an early phenomenon of iPD. Nonetheless, the mechanisms mediating the initiation and progression of retinal thinning in iPD are unknown.…”

Section: Discussionmentioning

confidence: 98%

“…Several cross‐sectional studies using OCT have demonstrated that, compared to age‐matched controls, PD patients have an atrophy of inner retina that seems to be associated with disease duration and motor disability 22 . More recent publications have shown that the thinning of macular GCIPL in PD is linked to cognitive impairment in de novo patients 23 and to the risk of dementia 18 . Interestingly, our group found that visual dysfunction in PD is selectively associated with the thinning of GCIPL in the 1‐ to 3‐mm diameter ring area around the fovea (parafoveal GCIPL), 20 an OCT feature that has also been identified in patients with idiopathic rapid eye movement sleep behavior disorder—the earliest (prodromal) phase of LBD 24 .…”

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confidence: 99%

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Retinal Thickness Predicts the Risk of Cognitive Decline in Parkinson Disease

Murueta‐Goyena

Pino

Galdós

et al. 2020

Annals of Neurology

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Objective This study was undertaken to analyze longitudinal changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic Parkinson's disease (iPD). Methods Patients with Lewy body diseases were enrolled and prospectively evaluated at 3 years, including patients with iPD (n = 42), dementia with Lewy bodies (n = 4), E46K‐SNCA mutation carriers (n = 4), and controls (n = 17). All participants underwent Spectralis retinal optical coherence tomography and Montreal Cognitive Assessment, and Unified Parkinson's Disease Rating Scale score was obtained in patients. Macular ganglion cell–inner plexiform layer complex (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates were estimated with linear mixed models. Risk ratios were calculated to evaluate the association between baseline GCIPL and pRNFL thicknesses and the risk of subsequent cognitive and motor worsening, using clinically meaningful cutoffs. Results GCIPL thickness in the parafoveal region (1‐ to 3‐mm ring) presented the largest reduction rate. The annualized atrophy rate was 0.63μm in iPD patients and 0.23μm in controls (p < 0.0001). iPD patients with lower parafoveal GCIPL and pRNFL thickness at baseline presented an increased risk of cognitive decline at 3 years (relative risk [RR] = 3.49, 95% confidence interval [CI] = 1.10–11.1, p = 0.03 and RR = 3.28, 95% CI = 1.03–10.45, p = 0.045, respectively). We did not identify significant associations between retinal thickness and motor deterioration. Interpretation Our results provide evidence of the potential use of optical coherence tomography–measured parafoveal GCIPL thickness to monitor neurodegeneration and to predict the risk of cognitive worsening over time in iPD. ANN NEUROL 2021;89:165–176

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Retinal Thickness Predicts the Risk of Cognitive Decline in Parkinson Disease

Murueta‐Goyena

Pino

Galdós

et al. 2020

Annals of Neurology

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“… 7 Noninvasive retinal imaging in neurodegenerative disorders, including Lafora disease, enables identification of early disease states and provides new opportunities to monitor disease progression. 8 , 9 …”

Section: Discussionmentioning

confidence: 99%

“…Noninvasive retinal imaging has been used to demonstrate retinal alterations in a number of neurodegenerative diseases. 7 , 8 , 9 , 10 , 11 Here we used spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO) in three genetically confirmed individuals with Lafora disease to look for similar retinal structural changes.…”

Section: Introductionmentioning

confidence: 99%

Retinal alterations in patients with Lafora disease

Heitkotter

Linderman

Cava

et al. 2021

American Journal of Ophthalmology Case Reports

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Purpose Lafora disease is a genetic neurodegenerative metabolic disorder caused by insoluble polyglucosan aggregate accumulation throughout the central nervous system and body. The retina is an accessible neural tissue, which may offer alternative methods to assess neurological diseases quickly and noninvasively. In this way, noninvasive imaging may provide a means to characterize neurodegenerative disease, which enables earlier identification and diagnosis of disease and the ability to monitor disease progression. In this study, we sought to characterize the retina of individuals with Lafora disease using non-invasive retinal imaging. Methods One eye of three individuals with genetically confirmed Lafora disease were imaged with optical coherence tomography (OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO). When possible, OCT volume and line scans were acquired to assess total retinal thickness, ganglion cell-inner plexiform layer thickness, and outer nuclear layer + Henle fiber layer thickness. OCT angiography (OCTA) scans were acquired in one subject at the macula and optic nerve head (ONH). AOSLO was used to characterize the photoreceptor mosaic and examine the retinal nerve fiber layer (RNFL). Results Two subjects with previous seizure activity demonstrated reduced retinal thickness, while one subject with no apparent symptoms had normal retinal thickness. All other clinical measures, as well as parafoveal cone density, were within normal range. Nummular reflectivity at the level of the RNFL was observed using AOSLO in the macula and near the ONH in all three subjects. Conclusions This multimodal retinal imaging approach allowed us to observe a number of retinal structural features in all three individuals. Most notably, AOSLO revealed nummular reflectivity within the inner retina of each subject. This phenotype has not been reported previously and may represent a characteristic change produced by the neurodegenerative process.

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“…Many blinding diseases target cellular populations in the retina, and in vivo imaging approaches in mice have been used to study optic nerve injury 1 , 3 , 4 , macular degeneration 13 , stroke 5 , glaucoma 2 , 6 , and uveitis 7 . Furthermore, many central nervous system neurodegenerative conditions manifest in the retina including Alzheimer's disease 39 , multiple sclerosis 40 , and Parkinson's disease 41 . Therefore, this readily accessible technique for in vivo imaging of the retina can be applied as a tool to study a broad set of neurodegenerative conditions.…”

Section: Discussionmentioning

confidence: 99%

Transpupillary Two-photon In vivo Imaging of the Mouse Retina

Wang

McCracken

Williams

2021

JoVE

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The retina transforms light signals from the environment into electrical signals that are propagated to the brain. Diseases of the retina are prevalent and cause visual impairment and blindness. Understanding how such diseases progress is critical to formulating new treatments. In vivo microscopy in animal models of disease is a powerful tool for understanding neurodegeneration and has led to important progress towards treatments of conditions ranging from Alzheimer's disease to stroke. Given that the retina is the only central nervous system structure inherently accessible by optical approaches, it naturally lends itself towards in vivo imaging. However, the native optics of the lens and cornea present some challenges for effective imaging access. This protocol outlines methods for in vivo two-photon imaging of cellular cohorts and structures in the mouse retina at cellular resolution, applicable for both acuteand chronic-duration imaging experiments. It presents examples of retinal ganglion cell (RGC), amacrine cell, microglial, and vascular imaging using a suite of labeling techniques including adeno-associated virus (AAV) vectors, transgenic mice, and inorganic dyes. Importantly, these techniques extend to all cell types of the retina, and suggested methods for accessing other cellular populations of interest are described. Also detailed are example strategies for manual image postprocessing for display and quantification. These techniques are directly applicable to studies of retinal function in health and disease.

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Inner retinal thinning as a biomarker for cognitive impairment in de novo Parkinson’s disease

Cited by 33 publications

References 46 publications

Retinal Thickness Predicts the Risk of Cognitive Decline in Parkinson Disease

Retinal Thickness Predicts the Risk of Cognitive Decline in Parkinson Disease

Retinal alterations in patients with Lafora disease

Transpupillary Two-photon In vivo Imaging of the Mouse Retina

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