Retinal Changes Identified in Incident and Prevalent Parkinson Disease

Siegfried Wagner, MD

Using data from 2 studies, a cross-sectional analysis showed that individuals with Parkinson disease (PD) have reduced thickness of the inner nuclear layer (INL) and ganglion cell-inner plexiform layer (GCIPL) of the retina. Collectively, these findings strengthened the argument that neurodegenerative pathology in PD involves the GCIPL and INL and that these retinal layers may have prognostic clinical relevance.

Published in Neurology, the detection of retinal markers in prevalent PD was collected through AlzeEye, a retrospective large-scale cohort, while the evaluation of such retinal markers were examined through participants from the UK Biobank. Led by Siegfried Wagner, MD, an honorary research fellow at the UCL Institute of Ophthalmology, macular retinal nerve fiber layer (mRNFL), GCIPL, and INL thickness were extracted from fovea-centered optical coherence tomography (OCT).

From the AlzeEye cohort of 154,830 individuals with retinal imagine, there were 700 individuals (0.45%) who had prevalent PD and 105,770 controls. After adjustment for age, sex, ethnicity, hypertension, and diabetes mellitus, individuals with prevalent PD had significantly thinner GCIPL across all parafoveal subfields (all inner: –2.12 μm; 95% CI, –3.17 to –1.07; P = 8.2 x 10^-5). Thickness point estimates were most reduced in the inferior subfield (–2.38 μm; 95% CI, –3.54 to –1.22; P = 6.0 x 10^-5) and least reduced in the temporal subfield (–1.75 μm; 95% CI, –2.82 to –0.68; P = .001).

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With regard to the findings of reduced INL and GCIPL, the investigators wrote that "It remains unclear whether such changes relate to the increased neurodegeneration found in the brains of individuals with Parkinson disease and resulting RTSD, or could represent a primary dopaminergic degeneration focused within the inner retina with anterior propagation of neurodegeneration. Further studies exploring the chronological sequence of retinal sublayer thickness would help elucidate the mechanism and determine whether retinal imaging could support the diagnosis, prognosis, and complex management of patients affected by Parkinson disease."

Across all subfields of the INL, patients with PD had significantly reduced thickness (all inner, –0.99; 95% CI, –1.52 to –0.47; P = 2.1 x 10^-4), with the most significant mark observed at the superior subfield (–1.09 μm; –1.70 to –0.47; P = 5.9 x 10^-4). Of note, there was limited evidence of reduced mRNFL thickness and prevalent PD with only a weak association seen for the inner temporal subfield (–0.69 μm; 95% CI, –1.37 to –0.02; P = .045). When excluding individuals with diabetes mellitus, effect measures were slightly reduced, but significant association between PD and the thickness of both the GCIPL (all inner, –1.79 μm; 95% CI, –3.30 to –0.27; P = .020) and INL (all inner, –0.85 μm; 95% CI, ­–1.58 to –0.13; P = .022). The lack of association between mRNFL and prevalent PD continued in this subgroup (all inner, –0.36 μm; 95% CI, –1.30 to 0.57; P = .45).

A total of 50,405 individuals from the UK Biobank had images of sufficient quality for the retinal marker analysis and fit the inclusion criteria. Of these, 53 individuals developed PD during the study period. Regarding retinal markers, reduced thickness of the GCIPL was associated with incident PD (HR, 0.62; 95% CI, 0.46-0.84 per SD increase; P = .002). There was also some evidence that thinner INL was associated with incident PD, especially at the inferior subfield (HR, 0.66; 95% CI, 0.51-0.86; P = .002). These associations persisted even when all those who developed PD in the first 24 months after having had retinal imaging were excluded.

REFERENCE
1. Wagner SK, Romero-Bascones D, Borja M, et al. Retinal optical coherence tomography features associated with incident and prevalent Parkinson disease. Neurology. Published online August 21, 2023. doi:10.1212/WNL.00000000000000207727