Retinal Nerve Fiber Layer Thickness and Associations With Cognitive Impairment in Parkinson’s Disease

Chang, Zihan; Xie, Fei; Li, Hualing; Yuan, Feilan; Zeng, Lirong; Shi, Lin; Zhu, Shuchai; Lu, Xiaoyan; Wei, Xiaobo; Wang, Qing

doi:10.3389/fnagi.2022.832768

Cited by 7 publications

(5 citation statements)

References 64 publications

(85 reference statements)

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“…AD patients showed a significant thickness reduction in global and temporal superior quadrants in the peripapillary RNFL [32]. Moreover, PD patients also displayed RNFL thinning [33], and a significant reduction in the RNFL thickness has been observed in the inferior sector [34]. This quadrant was also affected in our study in HD pre-symptomatic carriers.…”

Section: Discussionsupporting

confidence: 59%

Structural Abnormalities of the Optic Nerve and Retina in Huntington’s Disease Pre-Clinical and Clinical Settings

Mazur-Michałek

Kowalska

Zielonka

et al. 2022

IJMS

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Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. HD-related pathological remodelling has been reported in HD mouse models and HD carriers. In this study, we studied structural abnormalities in the optic nerve by employing Spectral Domain Optical Coherence Tomography (SD-OCT) in pre-symptomatic HD carriers of Caucasian origin. Transmission Electron Microscopy (TEM) was used to investigate ultrastructural changes in the optic nerve of the well-established R6/2 mouse model at the symptomatic stage of the disease. We found that pre-symptomatic HD carriers displayed a significant reduction in the retinal nerve fibre layer (RNFL) thickness, including specific quadrants: superior, inferior and temporal, but not nasal. There were no other significant irregularities in the GCC layer, at the macula level and in the optic disc morphology. The ultrastructural analysis of the optic nerve in R6/2 mice revealed a significant thinning of the myelin sheaths, with a lamellar separation of the myelin, and a presence of myelonoid bodies. We also found a significant reduction in the thickness of myelin sheaths in peripheral nerves within the choroids area. Those ultrastructural abnormalities were also observed in HD photoreceptor cells that contained severely damaged membrane disks, with evident vacuolisation and swelling. Moreover, the outer segment of retinal layers showed a progressive disintegration. Our study explored structural changes of the optic nerve in pre- and clinical settings and opens new avenues for the potential development of biomarkers that would be of great interest in HD gene therapies.

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Section: Discussionsupporting

confidence: 59%

Structural Abnormalities of the Optic Nerve and Retina in Huntington’s Disease Pre-Clinical and Clinical Settings

Mazur-Michałek

Kowalska

Zielonka

et al. 2022

IJMS

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“…There are some inherent limitations of our MR study. First, observational studies indicate that PD may only be associated with changes in RNFL and GCIPL thickness in specific quadrants rather than an overall change 25 . However, we were unable to obtain quadrant-specific summary data of RNFL and GCIPL thickness and therefore could not further perform subgroup analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Some observational studies indicate that the retinas of patients with PD show degenerative alterations characterized by decreased thickness in the Retinal Nerve Fiber Layer (RNFL) and the Ganglion Cell-Inner Plexiform Layer (GCIPL) 20 – 22 . Such alterations correlate with both motor 23 and non-motor symptoms of PD 24 , 25 .…”

Section: Introductionmentioning

confidence: 93%

Mendelian randomization reveals association between retinal thickness and non-motor symptoms of Parkinson’s disease

Zhou,

Shen,

Huang

et al. 2023

npj Parkinsons Dis.

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Retinal thickness is related to Parkinson’s disease (PD), but its association with the severity of PD is still unclear. We conducted a Mendelian randomized (MR) study to explore the association between retinal thickness and PD. For the two-sample MR analysis, the summary statistics obtained from genome-wide association studies on the thickness of Retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) were employed as exposure, while the summary statistics associated with PD were used as the outcome. The primary approach utilized was inverse variance weighted. To correct for multiple testing, the false discovery rate (FDR) was employed. For sensitivity analysis, an array of robust MR methods was utilized. We found genetically predicted significant association between reduced RNFL thickness and a reduced risk of constipation in PD (odds ratio [OR] = 0.854, 95% confidence interval [CI] (0.782, 0.933), P < 0.001, FDR-corrected P = 0.018). Genetically predicted reduced RNFL thickness was associated with a reduced Unified Parkinson’s Disease Rating Scale total score (β = −0.042, 95% CI (−0.079, 0.005), P = 0.025), and reduced GCIPL thickness was associated with a lower risk of constipation (OR = 0.901, 95% CI (0.821, 0.988), P = 0.027) but a higher risk of depression (OR = 1.103, 95% CI (1.016, 1.198), P = 0.020), insomnia (OR = 1.090, 95% CI (1.013, 1.172), P = 0.021), and rapid eye movement sleep behaviour disorder (RBD) (OR = 1.198, 95% CI (1.061, 1.352), P = 0.003). In conclusion, we identify an association between retinal thickness and non-motor symptoms (constipation, depression, insomnia and RBD) in PD, highlighting the potential of retinal thickness as a biomarker for PD nonmotor symptoms.

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“…With the OCT technique, thinning of retinal nerve fibers has been found in patients with Parkinson's disease [71][72][73].…”

Section: Structural Changes In the Retina Of Pdmentioning

confidence: 99%

Retinal Alterations Predict Early Prodromal Signs of Neurodegenerative Disease

Casciano,

Zauli,

Celeghini

et al. 2024

IJMS

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Neurodegenerative diseases are an increasingly common group of diseases that occur late in life with a significant impact on personal, family, and economic life. Among these, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the major disorders that lead to mild to severe cognitive and physical impairment and dementia. Interestingly, those diseases may show onset of prodromal symptoms early after middle age. Commonly, the evaluation of these neurodegenerative diseases is based on the detection of biomarkers, where functional and structural magnetic resonance imaging (MRI) have shown a central role in revealing early or prodromal phases, although it can be expensive, time-consuming, and not always available. The aforementioned diseases have a common impact on the visual system due to the pathophysiological mechanisms shared between the eye and the brain. In Parkinson’s disease, α-synuclein deposition in the retinal cells, as well as in dopaminergic neurons of the substantia nigra, alters the visual cortex and retinal function, resulting in modifications to the visual field. Similarly, the visual cortex is modified by the neurofibrillary tangles and neuritic amyloid β plaques typically seen in the Alzheimer’s disease brain, and this may reflect the accumulation of these biomarkers in the retina during the early stages of the disease, as seen in postmortem retinas of AD patients. In this light, the ophthalmic evaluation of retinal neurodegeneration could become a cost-effective method for the early diagnosis of those diseases, overcoming the limitations of functional and structural imaging of the deep brain. This analysis is commonly used in ophthalmic practice, and interest in it has risen in recent years. This review will discuss the relationship between Alzheimer’s disease and Parkinson’s disease with retinal degeneration, highlighting how retinal analysis may represent a noninvasive and straightforward method for the early diagnosis of these neurodegenerative diseases.

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Retinal Nerve Fiber Layer Thickness and Associations With Cognitive Impairment in Parkinson’s Disease

Cited by 7 publications

References 64 publications

Structural Abnormalities of the Optic Nerve and Retina in Huntington’s Disease Pre-Clinical and Clinical Settings

Structural Abnormalities of the Optic Nerve and Retina in Huntington’s Disease Pre-Clinical and Clinical Settings

Mendelian randomization reveals association between retinal thickness and non-motor symptoms of Parkinson’s disease

Retinal Alterations Predict Early Prodromal Signs of Neurodegenerative Disease

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