Keeping an eye on Parkinson's disease: color vision and outer retinal thickness as simple and non-invasive biomarkers

Abstract

Over the last two decades, visual symptoms and retinal changes in Parkinson's disease (PD) have emerged as important biomarkers. Color vision deficiency, which begins in the outer retina, has been increasingly investigated, but a focused review of these papers has not recently been conducted. Similarly, thinning of the outer retina as measured using optical coherence tomography (OCT) holds potential as a screening marker for PD, particularly as these devices are already commonplace in community and hospital settings. Moreover, outer retinal thinning may be more specific for Parkinson's disease as inner retinal changes also occur in more common neurodegenerative diseases like glaucoma and Alzheimer's disease. This review summarizes contemporary evidence on two outer retina focused measures, color vision and outer retinal thickness, which can be readily quantified using non-invasive approaches and thus examines their potential as biomarkers for screening, detection, and progression in PD.

Keywords: Neurodegenerative disorders; Optical coherence tomography; Parkinsonism; Visual impairment.

Fig. 1

Common clinical color vision tests. a Ishihara test (24-plate edition 2011, Kanehara Trading Inc., Tokyo, Japan); b Farnsworth–Munsell 100-Hue test (FM 100-Hue, X-Rite, Grand Rapids, MI, USA); c Anomaloscope test (OT-II, Neitz Instruments Co., Ltd., Tokyo, Japan)

Fig. 2

Forest plot showing Cohen’s d effect size (95% CI) on color vision discrimination tests. Each study is represented by a dot (mean Cohen’s d) with error bars (95% CI). Positive values suggest higher error scores in the PD (or iRBD) group compared to healthy controls. Asterisks (*) indicate significant differences between groups; ^#1 and ^#2 represent the first and the second FM- 100 test, respectively; CI, confidence interval; PD, Parkinson’s disease; iRBD, idiopathic rapid eye movement sleep behavior disorder; FM- 100, Farnsworth-Munsell 100-Hue test; Lanthony-D15, Lanthony Desaturated 15-Hue Test

Fig. 3

A representative single-line OCT scan. a An enface image of the posterior retina. The yellow circle represents the macular region of the retina, 6 mm X 6 mm in size. The green line indicates the path of a single macular OCT line scan displayed in panel (b). b A cross-sectional (B-scan) OCT image of the posterior retina in the horizontal meridian. The cross-sectional OCT image returns retinal layers including the inner retina: RNFL (black layer), retinal nerve fiber layer; GCL (orange layer), ganglion cell layer; IPL (beige layer), inner plexiform layer; INL (yellow layer), inner nuclear layer; and the outer retina: OPL (green layer), outer plexiform layer; ONL (light-blue layer), outer nuclear layer; PRL (dark-blue layer), photoreceptors (rods and cones) layer; RPE (pink layer), retinal pigment epithelium. The macular region is a key area which is responsible for visual acuity and color vision. There are three main types of neurons in the retina located in different layers: 1. photoreceptor cells (dendrites PRL, somas in ONL, and axons in OPL); 2. bipolar cells (dendrites in OPL, somas in INL, and axons in IPL); 3. ganglion cells (dendrites in IPL, somas in GCL, and axons in RNFL), and visual signals are transmitted from outermost to innermost layer of the retina

Fig. 4

Forest plot showing Cohen’s d effect size (95% CI) in studies reporting the thickness of individual outer retinal layers [a OPL, b ONL, c PRL, and d RPE]. Each study is represented by a dot (mean Cohen’s d) with error bars (95% CI). Positive values represent thickening of the layers in the PD or iRBD group compared to healthy controls, while negative values suggest thinning of the layer. Asterisks (*) indicate significant differences between groups; ^#1 and ^#2 represent unilateral PD and bilateral PD, respectively; CI Confidence interval; PD Parkinson’s disease; iRBD idiopathic rapid eye movement sleep behavior disorder