Dynamics of retinal changes in early-stage Parkinson's disease

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder primarily characterized by motor symptoms, with emerging evidence suggesting retinal pathology, particularly in the ganglion cell-inner plexiform layer (GCIPL), detectable via optical coherence tomography (OCT). This study aimed to characterize early retinal dynamics in PD using OCT. We conducted a prospective one-year longitudinal multicenter study involving 53 early-stage PD patients with a disease duration of 5 years or less and 52 controls. The participants underwent retinal spectral-domain OCT, primary visual function and cognitive examinations. We examined baseline retinal measures and short-term longitudinal differences between groups via linear mixed effects models. In PD patients, the baseline GCIPL thickness in central regions was increased by up to 4 μm, and the rate of thinning in the parafoveal GCIPL was - 0.61 [0.29] µm/year faster over a one-year follow-up period than in controls in the 2- to 3-mm ring (p = 0.039). In PD patients, greater central GCIPL thickness was associated with poorer contrast sensitivity and reduced performance on the Farnsworth D15 color vision test. It also predicted subsequent thinning in both the GCIPL (2- to 3-mm ring) and the inner nuclear layer (2- to 5-mm rings). However, this increased thickness was not linked to prevalent or progressive motor or cognitive manifestations. In conclusion, this study provides the first detailed topographical description of early retinal dynamics in PD patients, revealing increased central GCIPL thickness and accelerated parafoveal GCIPL thinning in PD. However, the macular region shows complex and variable dynamics among PD patients, but these changes precede detectable progression in clinical scales.

Keywords: Fovea; Ganglion cell-inner plexiform layer; Optical coherence tomography; Parkinson’s disease; Retina.

Fig. 1

Study flowchart. Description of the follow-up design of the study participants. Lost to follow-up with reasons in each stage is represented with dashed arrows. Abbreviations: DM, diabetes mellitus; PD, Parkinson’s disease

Fig. 2

Baseline retinal differences between PD patients and controls. (A) A funduscopic SLO image with superimposed macular parcellation into concentric rings centered on the fovea. Continuous lines represent the ETDRS grid annuli (with diameters of 1-mm, 3-mm, and 6-mm), while dashed lines indicate the additional macular subdivisions introduced in this study, dividing the macula into concentric circular zones spaced 1-mm apart. The blue line represents the region where the B-scan shown in B was acquired. (B) A horizontal OCT B-scan passing through the fovea. The GCIPL layer is highlighted in blue. (C) The circular plot on the left illustrates estimated differences in GCIPL thickness between PD patients and controls at baseline. The combined boxplots and half violin plots on the right depict the distribution of the mean GCIPL thickness across different macular regions for each group. Statistically significant differences are indicated with asterisks (**p < 0.01) Abbreviations: ETDRS, Early Treatment Diabetic Retinopathy Study; GCIPL: ganglion cell–inner plexiform layer complex; OCT, Optical Coherence Tomography; SLO, Scanning Laser Ophthalmoscopy

Fig. 3

Linear mixed-effects model estimates of baseline and longitudinal retinal thickness. PD patients were divided into tertiles according to their baseline central GCIPL thickness, and PD patients in the upper and lower tertiles were compared. The parameter estimates from linear mixed-effects models show the difference in thickness between the upper and lower tertiles at baseline (upper panels) and the rate of change over the 1-year follow-up period (lower panels). Significant p-values are indicated by asterisks (*p < 0.05; **p < 0.01; ***p < 0.001) Abbreviations: GCIPL: ganglion cell–inner plexiform layer complex; INL, inner nuclear layer; PD, Parkinson’s disease