Bidirectional retinal oculomics in Parkinson’s disease: A cross-sectional analysis of two cohorts

Abstract

Purpose : Dopaminergic impairment in Parkinson’s disease (PD) has been observed in the retina in cadaveric studies however it remains unclear whether this can be detected by in vivo imaging. We investigated inner retinal anatomy, measured using optical coherence tomography (OCT), in prevalent PD and subsequently assessed these markers as prognostic factors for the development of PD using a prospective research cohort.

Methods : This cross-sectional analysis used data from two studies. For the detection of retinal markers in prevalent PD, we used data from AlzEye, a retrospective cohort of 154,830 patients aged 40 years and over attending ophthalmic hospitals in London, UK from 2008-2018. For the evaluation of retinal markers as prognostic factors, we used data from United Kingdom Biobank (UKBB), a prospective population-based cohort where 67,311 volunteers aged 40-69 years were recruited from 2006-2010 and underwent retinal imaging. Retinal nerve fibre layer, ganglion cell-inner plexiform layer (mGC-IPL), and inner nuclear layer (INL) thicknesses were extracted from macula-centred OCT. Linear mixed effects models were fitted to examine the association between prevalent PD and retinal thicknesses. Hazard ratios (HR) for the association between time to PD diagnosis and retinal thicknesses were estimated using frailty models.

Results : Within the AlzEye cohort, there were 700 individuals with prevalent PD and 105,770 controls (mean age 65.5 +/- 13.5 years, 51.7% female). Individuals with prevalent PD had thinner mGC-IPL (-2.12 μm, 95%CI: -3.17, -1.07, p = 8.2×10^-5) and INL (-0.99 μm, 95%CI: -1.52, -0.47, p = 2.1×10^-4). The UKBB included 50,405 participants (mean age 56.1 +/- 8.2 years, 54.7% female), of whom 53 developed PD at a mean of 2653 +/- 851 days. Thinner mGC-IPL (HR: 0.62 per standard deviation increase, 95%CI: 0.46, 0.84, p=0.002) and thinner INL (HR: 0.70, 95%CI: 0.51, 0.96, p=0.026) were also associated with incident PD.

Conclusions : Our novel findings of reduced INL thickness in PD lend credence to a primary dopaminergic degeneration originating within the inner retina. Differences in thicknesses of the INL and mGC-IPL manifest early highlighting a potential role for retinal imaging for early detection and at-risk stratification for PD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Summary of findings for prevalent and incident Parkinson’s disease. Values are shown per parafoveal region and for the average of all inner segments (small donut).