Assessing Retinal Structure in Patients with Parkinson's Disease

Abstract

Objective: The retina is an extension of the central nervous system (CNS), and ocular symptoms can precede manifestations of CNS disorders. Given that several neurodegenerative conditions that affect the brain exhibit ocular symptoms, the retina may be an accessible biomarker to monitor disease progression. Dopamine, the key neurotransmitter related to Parkinson's disease (PD), is contained in amacrine and interplexiform cells, which reside in specific retinal layers. Understanding how loss of dopaminergic cells affects retinal anatomy could be relevant for monitoring disease progression. Here, our objective is to evaluate retinal structure (foveal pit morphology and thickness) in patients with PD.

Methods: Thirty-three Caucasian subjects diagnosed with PD and 40 age-matched Caucasian control subjects underwent retinal imaging with spectral-domain optical coherence tomography (SD-OCT). Axial length measurements were used to correct the lateral scale of each macular volume scan. From these corrected volumes, foveal morphology was quantified with previously described algorithms, and Early Treatment Diabetic Retinopathy Study (ETDRS) grids of retinal thickness were generated and incorporated into a logistic regression model to predict PD.

Results: Interocular foveal morphology measurements were highly symmetrical in PD patients and control subjects. There were no significant differences in foveal pit morphology between PD patients and control subjects. Using a model incorporating sex and axial length corrected ETDRS regions, we generated a receiver operating characteristic curve with a C-statistic of 0.80.

Conclusion: Our study, which to our knowledge is the first to properly scale OCT measurements when quantifying retinal thickness, demonstrates that PD patients retain foveal symmetry between eyes. When constructing a model to predict PD, sex, along with the center 1 mm and temporal outer ETDRS regions, were significant predictors of PD. In addition to proper scaling of OCT measures, gender and racial differences in retinal anatomy should be considered in building future predictive PD models when using OCT.

Keywords: Fovea; Optical coherence tomography; Parkinson’s disease; Retina.

Figure 1

Interocular symmetry of foveal morphology in HC Subjects (A, C, E, G)) and PD Patients (B, D, F, H). Bland-Altman plots for foveal pit depth (A, B), diameter (C, D), slope (E, F), and volume (G, H). For PD patients, the absolute mean difference between eyes (OD minus OS; solid line in each plot) was less than 0.0019 mm for pit depth, less than 0.0171 mm for pit diameter, less than 0.095 degrees for foveal slope, and less than 0.0029 mm³ for foveal volume. For HC subjects, the absolute mean difference was less than 0.0007 mm for pit depth, less than 0.0095 mm for pit diameter, less than 0.2063 degrees for foveal slope, and less than .0006 mm3 for foveal volume. The mean difference is represented by the solid black line, while the dashed lines represent the 95% limits of agreement (LOA) for the bias. Shaded regions represent the confidence limits on the bias and LOA. There was no apparent relationship between the mean difference and the magnitude of the measurement.

Figure 2

Ocular biometry corrected Early Treatment Diabetic Retinopathy Study (ETDRS) thickness maps for HC subjects and PD patients. PD patients have thinner retinas compared to HC subjects. The ETDRS measurements of all eyes were included in the analysis to help establish collinear predictors of PD. The measurements of all ETDRS regions were highly correlative as shown in Supplementary Table 2.

Figure 3

Receiver operating characteristic (ROC) curve using logistic regression models to predict PD. This model incorporates sex, temporal outer, and the center 1mm ETDRS region to predict PD. The cross-validated C-statistic is 0.799 (see methods), with a 95% confidence interval of 0.7928 to 0.8046. We additionally calculated the odds ratio estimates for these three effects. Sex, temporal outer, and the center 1mm ETDRS region had point estimates (and 95% Wald confidence limits) of 0.094 (0.036 and 0.248), 0.948 (0.907 and 0.990), and 0.963 (0.937 and 0.990), respectively. All p-values were less than 0.05 for these effects.