Reduced Thickness of the Retina in de novo Parkinson's Disease Shows A Distinct Pattern, Different from Glaucoma.

Background: Parkinson's disease (PD) patients experience visual symptoms and retinal degeneration. Studies using optical coherence tomography (OCT) have shown reduced thickness of the retina in PD, also a key characteristic of glaucoma. Objective: To identify the presence and pattern of retinal changes in de novo, treatment-naive PD patients compared to healthy controls (HC) and early primary open angle glaucoma (POAG) patients. Methods: Macular OCT data (10×10 mm) were collected from HC, PD, and early POAG patients, at the University Medical Center Groningen. Bayesian informative hypotheses statistical analyses were carried out comparing HC, PD-, and POAG patients, within each retinal cell layer. Results: In total 100 HC, 121 PD, and 78 POAG patients were included. We showed significant reduced thickness of the inner plexiform layer and retinal pigment epithelium in PD compared to HC. POAG patients presented with a significantly thinner retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, outer plexiform layer, and outer photoreceptor and subretinal virtual space compared to PD. Only the outer segment layer and retinal pigment epithelium were significantly thinner in PD compared to POAG. Conclusions: De novo PD patients show reduced thickness of the retina compared to HC, especially of the inner plexiform layer, which differs significantly from POAG, showing a more extensive and widespread pattern of reduced thickness across layers. OCT is a useful tool to detect retinal changes in de novo PD, but its specificity versus other neurodegenerative disorders has to be established.

Study protocol of the DUtch PARkinson Cohort (DUPARC): a prospective, observational study of de novo Parkinson's disease patients for the identification and validation of biomarkers for Parkinson's disease subtypes, progression and pathophysiology.

BACKGROUND: Parkinson's Disease (PD) is a heterogeneous, progressive neurodegenerative disorder which is characterized by a variety of motor and non-motor symptoms. To date, no disease modifying treatment for PD exists. Here, the study protocol of the Dutch Parkinson Cohort (DUPARC) is described. DUPARC is a longitudinal cohort study aimed at deeply phenotyping de novo PD patients who are treatment-naïve at baseline, to discover and validate biomarkers for PD progression, subtypes and pathophysiology. METHODS/DESIGN: DUPARC is a prospective cohort study in which 150 de novo PD subjects will be recruited through a collaborative network of PD treating neurologists in the northern part of the Netherlands (Parkinson Platform Northern Netherlands, PPNN). Participants will receive follow-up assessments after 1 year and 3 years, with the intention of an extended follow-up with 3 year intervals. Subjects are extensively characterized to primarily assess objectives within three major domains of PD: cognition, gastrointestinal function and vision. This includes brain magnetic resonance imaging (MRI); brain cholinergic PET-imaging with fluoroethoxybenzovesamicol (FEOBV-PET); brain dopaminergic PET-imaging with fluorodopa (FDOPA-PET); detailed neuropsychological assessments, covering all cognitive domains; gut microbiome composition; intestinal wall permeability; optical coherence tomography (OCT); genotyping; motor and non-motor symptoms; overall clinical status and lifestyle factors, including a dietary assessment; storage of blood and feces for additional analyses of inflammation and metabolic parameters. Since the start of the inclusion, at the end of 2017, over 100 PD subjects with a confirmed dopaminergic deficit on FDOPA-PET have been included. DISCUSSION: DUPARC is the first study to combine data within, but not limited to, the non-motor domains of cognition, gastrointestinal function and vision in PD subjects over time. As a de novo PD cohort, with treatment naïve subjects at baseline, DUPARC provides a unique opportunity for biomarker discovery and validation without the possible confounding influences of dopaminergic medication. TRIAL REGISTRATION: NCT04180865; registered retrospectively, November 28th 2019.

Retinal layers in Parkinson's disease: A meta-analysis of spectral-domain optical coherence tomography studies.

BACKGROUND: Patients with Parkinson's disease experience visual symptoms, partially originating from retinal changes. Since 2011, multiple case-control studies using spectral-domain OCT, which allows for studying individual retinal layers, have been published. The aim of this study was to substantiate the occurrence, extent, and location of retinal degeneration in Parkinson's by meta-analysis. METHODS: Spectral-domain OCT case-control data were collected by performing a search in PubMed and Embase with terms: "optical coherence tomography" and "parkinson", up to November 5th, 2018. Studies with fewer than 10 patients or controls were excluded. We performed a random effects meta-analysis. Heterogeneity was evaluated with I2 statistics; publication bias with Egger's and Begg's tests. RESULTS: Out of 77 identified studies, 36 were included, totaling 1916 patients and 2006 controls. A significant thinning of the peripapillary retinal nerve fiber layer (d = -0.42; 95% confidence interval -0.54 to -0.29) and the combined ganglion cell and inner plexiform layers (d = -0.40; -0.72, to -0.07) was found. The inner nuclear layer and outer plexiform layer did not show significant changes. Heterogeneity ranged from 3 to 92%; no publication bias was found. CONCLUSIONS: Parkinson's patients show significant thinning of the inner retinal layers, resembling changes found in glaucoma and other neurodegenerative diseases like Alzheimer's. Study of different cell layers in-vivo is possible by moving from time-to spectral domain OCT. Retinal degeneration may be affiliated with neurodegenerative pathology overall, and could serve as a biomarker in neurodegenerative disorders. Longitudinal research including clinical correlations is needed to determine usefulness in Parkinson's disease.