Central retina changes in Parkinson’s disease: a systematic review and meta-analysis

Huang, Lele; Zhang, Dan; Ji, Jianling; Wang, Yujie; Zhang, Ruijun

doi:10.1007/s00415-020-10304-9

Cited by 42 publications

(44 citation statements)

References 54 publications

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“…Two recent reviews and meta-analyses have reported a thinning of the inner retinal layers and the pRNFL as prominent features in the eyes of Parkinson's patients. 17,18 Other groups also found significant thinning of pRNFL in PD compared to HC, 17,19,20 however the authors pointed out that their analysis gathered results from patients with different stages of Parkinson's disease. We found no significant difference in the pRNFL thickness between patients with PD and HC (Table 2).…”

Section: Discussionmentioning

confidence: 99%

The Retinal Posterior Pole in Early Parkinson’s Disease: A Fundus Perimetry and SD-OCT Study

Cesareo

Marco

Giannini

et al. 2021

OPTH

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To assess the structure and function of the retinal posterior pole in patients with early Parkinson's disease (PD) and to identify possible biomarkers correlated with clinical features. Patients and Methods: A cross-sectional case-control study of 21 patients with PD and 22 age-matched healthy controls (HC) was conducted. All subjects underwent full ophthalmological examinations, fundus perimetry (FP) and spectral domain-OCT (SD-OCT) of the entire retinal posterior pole and peripapillary retinal nerve fiber layer (pRNFL). Results: We analyzed 41 eyes from 21 patients (14 males and 7 females) with early PD (Hoehn and Yahr scale (H&Y) equal to or less than stage 2) and 41 eyes from 22 HC (12 males and 10 females). We found no significant difference in the pRNFL thickness between patients with PD and HC. The statistical analysis of the SD-OCT posterior pole area, consisting of 64 values for each retinal layer, revealed a decrease in the outer nuclear layer (ONL) thickness in patients with PD (p < 0.0001). On the contrary, a significant increase in the thickness of the outer plexiform layer (OPL) (p < 0.0001) and of the retinal pigmented epithelium (RPE) (p= 0.002) compared to healthy controls was detected. Other retinal layers showed no significant statistical differences. The differential light sensitivity (DLS) values measured by FP were significantly lower in patients than the healthy controls (15 [13-16.2] vs 17.95 [16.08-18.96] p<0.0001). Conclusion:Our results showed that DLS and retinal structure differed in the posterior pole between patients with early PD and controls. Thickening of the OPL may represent accumulation of α-synuclein in the OPL of patients with PD.

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Section: Discussionmentioning

confidence: 99%

The Retinal Posterior Pole in Early Parkinson’s Disease: A Fundus Perimetry and SD-OCT Study

Cesareo

Marco

Giannini

et al. 2021

OPTH

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“…It could provide high-resolution images of the retina and precisely and objectively quantify discrete neuronal layers, including the peripapillary retinal nerve fiber layer (RNFL, representing the unmyelinated axons of retinal ganglion cells), retinal ganglion cell bodies and the inner plexiform layer (GCIP, representing the health of the ganglion cell layer). This technique has been applied to detect neuroaxonal retinal abnormalities in neurodegenerative disease like Parkinson's Disease (Huang et al, 2020 ), progressive supranuclear palsy (Schneider et al, 2014 ), multiple system atrophy (Schneider et al, 2014 ) and Alzheimer's disease (Kirbas et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Selective and Inverse U-Shaped Curve Alteration of the Retinal Nerve in Amyotrophic Lateral Sclerosis: A Potential Mirror of the Disease

Zhang

Liu

et al. 2022

Front. Aging Neurosci.

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Introduction: Alterations in the visual pathway involving the retina have been reported in amyotrophic lateral sclerosis (ALS) but they lack consistency and subgroup analysis. We aimed to assess the retinal nerve fiber layer (RNFL) and retinal ganglion cells (RGCs) alterations in different stages of ALS patients and their association with ALS progression parameters.Methods: The study population consisted of 70 clinically diagnosed ALS patients and 55 age, sex matched controls. All of them underwent ophthalmic assessments and optical coherence tomography imaging. Four quadrants of the peripapillary RNFL and ganglion cell/inner plexiform complex (GCIP) were observed and automatically measured. Early-stage distal motor neuron axon dysfunction in ALS was detected by compound muscle action potential (CMAP) of the distal limbs within 12 months. The ALS disease parameters included the ALSFRS-R score and the disease progression rate (ΔFS).Results: Generally compared with controls, the nasal (p = 0.016) quadrant of the RNFL was thicker in ALS patients. When controlling for age and ΔFS, the RNFL(r = 0.37, p = 0.034) and GCIP(r = 0.40, p = 0.021) were significantly thickened as disease progressed within 12 months, while the RNFL declined with time after one year (r = −0.41, p = 0.037). ALS patients was subclassified into thickened RNFL (T-RNFL, >95th percentile of normal), impaired RNFL (I-RNFL, <5th percentile of normal) and normal RNFL. There were significant differences in the GCIP among the three groups (p < 0.001). In the T-RNFL group (n = 18), the RNFL was negatively correlated with the abductor pollicis brevis-CMAP amplitude within 12 months (r = −0.56, p = 0.01). Patients within 12 months in this group progressed faster than others (p = 0.039). In the normal RNFL group (n = 22), 13 patients were diagnosed beyond 12 months, whose ΔFS was remarkably lower (p = 0.007). In I-RNFL group (n = 30), the early stage patients (<12 months) had significant higher ΔFS (p = 0.006). One patient was with SOD1 pathogenic variant (p.A5V).Conclusion: Alterations of retinal nerve were not consistent in ALS patients with diverse phenotypes and progression rates. Generally speaking, the RNFL thickened during the first year and then gradually declined, which is related to but preceding the thickness change of the RGCs. Patients with a significant RNFL thinning in the early stage may have a faster progression rate. The inverse U-shaped curve transformation might be in accordance with early-stage motor neuron axonopathy.

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“…Optical coherence tomography (OCT) as a marker for PD is gaining increasing interest, given its widespread availability and capacity for differentiating cell classes at micron resolution. In the human literature, meta-analyses show that consistent thinning in foveal thickness (which primarily contains outer retinal neurons) and the retinal nerve fibre layer have been reported 25 , 26 . However, no studies have examined OCT in an MPTP model or modification with L-DOPA treatment which may inform understanding of dopamine driven changes.…”

Section: Introductionmentioning

confidence: 94%

Characterization of retinal function and structure in the MPTP murine model of Parkinson’s disease

Tran

Wong

Lim

et al. 2022

Sci Rep

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In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson’s disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, ERG), retinal structure (optical coherence tomography, OCT) and retinal dopaminergic cell number (tyrosine hydroxylase immunohistochemistry, IHC) at two time points (21 and 45 days) post MPTP model induction. We also investigate the effect of levodopa (L-DOPA) as a proof-of-principle chronic intervention against MPTP-induced changes in the retina. We show that MPTP decreases dopaminergic amacrine cell number (9%, p < 0.05) and that a component of the ERG that involves these cells, in particular oscillatory potential (OP) peak timing, was significantly delayed at Day 45 (7–13%, p < 0.01). This functional deficit was paralleled by outer plexiform layer (OPL) thinning (p < 0.05). L-DOPA treatment ameliorated oscillatory potential deficits (7–13%, p < 0.001) in MPTP animals. Our data suggest that the MPTP toxin slows the timing of inner retinal feedback circuits related to retinal dopaminergic pathways which mirrors findings from humans with PD. It also indicates that the MPTP model causes structural thinning of the outer retinal layer on OCT imaging that is not ameliorated with L-DOPA treatment. Together, these non-invasive measures serve as effective biomarkers for PD diagnosis as well as for quantifying the effect of therapy.

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Central retina changes in Parkinson’s disease: a systematic review and meta-analysis

Cited by 42 publications

References 54 publications

The Retinal Posterior Pole in Early Parkinson’s Disease: A Fundus Perimetry and SD-OCT Study

The Retinal Posterior Pole in Early Parkinson’s Disease: A Fundus Perimetry and SD-OCT Study

Selective and Inverse U-Shaped Curve Alteration of the Retinal Nerve in Amyotrophic Lateral Sclerosis: A Potential Mirror of the Disease

Characterization of retinal function and structure in the MPTP murine model of Parkinson’s disease

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