OCT Spots Retinal Changes Years Before Parkinson Disease Diagnosis

Reduced thickness of specific retinal layers may predict the onset of Parkinson disease (PD), according to study findings published in Neurology.

Researchers in the United Kingdom and Spain performed a cross-sectional analysis using data collected from 2 studies — a retrospective, real-world, cohort study (AlzEye) conducted between January 1, 2008 and April 1, 2018 and the prospective, population-based, multicenter, UK Biobank cohort study with data collected between 2006 and 2010.

The researchers measured the thickness of the inner nuclear layer (INL), the ganglion cell-inner plexiform layer (GCIPL), and the macular retinal nerve fiber layer (mRNFL) using optical coherence tomography (OCT).

In the AlzEye study, 700 participants had prevalent PD compared with 105,770 control individuals (mean age, 66; 51.7% women. Retrospectively, the researchers ascertained that individuals with prevalent PD demonstrated reduced thickness of the GCIPL (-2.12 μm; 95% CI, -3.17 to -1.07, P =.000082) and the INL (-0.99 μm; 95% CI, -1.52 to -0.47, P =.00021). Only a weak association was found between reduced thickness of the mRNFL and prevalent PD in the inner temporal subfield (-0.69 μm; 95% CI, -1.37 and -0.02, P =.045).

In the UK Biobank study, 53 of 50,405 participants (mean age, 56; 54.7% women) with adequate quality retinal images developed PD over an average of 2653±852 days. Reduced thickness of the GCIPL (hazard ratio [HR], 0.62; 95% CI, 0.46-0.84; P =.002) as well as the INL (HR, 0.70; 95% CI, 0.51-0.96; P =.026) was associated with higher risk of developing incident PD. The researchers found that this association was maintained even after excluding all of the individuals who developed PD within the first 24 months after retinal imaging. This suggests the value of using retinal imaging to predict PD risk.

Dopamine is a principal neuromodulator within retinal circuitry. Dopaminergic cells of the neurosensory retina are found primarily in the inner plexiform layer (IPL) and the INL, which regulate dopaminergic activity between AII amacrine cells, horizontal cells, and retinal ganglion cells.

One explanation for the connection between PD and decreased retinal thickness is the intracellular accumulation of toxic alpha-synuclein protein aggregates contributing to oxidative stress, mitochondrial damage, and eventual neurodegeneration of dopaminergic cells.

“Individuals with PD have reduced thickness of the INL and GCIPL of the retina,” the researchers concluded. “Involvement of these layers several years before clinical presentation highlight a potential role for retinal imaging for at-risk stratification of PD.”

Study limitations included lack of information about PD diagnosis date, PD status, treatment patterns, or current therapies, use of ICD-10 codes for PD diagnosis, and lack of retinal histological data to confirm the proposed protein aggregation hypothesis in the INL.