Markers that indicate the presence of Parkinson's disease (PD) in patients on average seven years before clinical presentation have been identified by a University College London (UCL) and Moorfields Eye Hospital research team, offering hope for pre-screening of those at risk of the disease.
Eye scans and data are known to reveal indications of hypertension and diabetes, for example, and scans have recently revealed signs of neurodegenerative conditions, such as Alzheimer's disease, multiple sclerosis, and schizophrenia.
This "emerging and exciting" field of research is known as 'oculomics', explained the authors of the new study, published in the journal Neurology.
High-resolution retinal images were now a routine part of eye care – in particular, a 3D scan known as 'optical coherence tomography' (OCT), which produces a detailed cross-section of down to a micrometre.
"These images are extremely useful for monitoring eye health, but their value goes much further, as a scan of the retina is the only non-intrusive way to view layers of cells below the skin's surface", the authors pointed out.
Thinner Retinal Cell Layers Associated with Parkinson's Disease
Cadaveric studies had shown disease-related neurodegeneration and other morphological abnormalities in the retina of individuals with PD – specifically, differences in the inner nuclear layer (INL), explained the authors. However, it remained unclear whether these could be reliably detected with in vivo imaging, they stressed.
For the cross-sectional analysis study the researchers investigated inner retinal anatomy — measured using OCT — in prevalent PD, and subsequently assessed the association of these markers with the development of the disease. They used two datasets – AlzEye, which combines the world's largest single institution retinal imaging database with nationally collected systemic data, to investigate retinal markers in prevalent PD, and the UK Biobank to investigate these in incident PD.
Macular retinal nerve fibre layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL), and inner nuclear layer (INL) thicknesses were extracted from fovea-centred OCT.
Within the AlzEye cohort, 700 individuals had prevalent PD and 105,770 controls – mean age 65.5, 51.7% female. Individuals with prevalent PD disease had thinner GCIPL (-2.12 μm) and INL (-0.99 μm).
The UK Biobank included 50,405 participants — mean age 56.1, 54.7% female — of whom 53 developed PD at up to a mean of 2653 +/-851 days. Thinner GCIPL (hazard ratio: 0.62 per SD increase) and thinner INL (hazard ratio: 0.70) were also associated with incident PD.
The authors highlighted that they had "confirmed previous reports" of a significantly thinner GCIPL associated with PD. However, for the first time, they had identified a thinner INL as also associated, which they highlighted was a "novel" finding. This was relevant, they stressed, because the INL represented the "hub" of dopaminergic activity in the neurosensory retina.
In addition, they found that the "reduced thickness of these layers" was also associated with increased risk of developing PD, "beyond that conferred" by other factors or comorbidities – age, sex, ethnicity, hypertension, and diabetes mellitus.
Potential Role for Retinal Imaging in Pre-Screening Those at Risk
The findings strengthen the argument that neurodegenerative pathology in PD involves the GCIPL and INL, and that these retinal layers might have "prognostic clinical relevance", the authors postulated.
"Individuals with Parkinson's disease have reduced thickness of the INL and GCIPL of the retina," they explained. The involvement of these layers several years before clinical presentation highlighted a potential role for retinal imaging for at-risk stratification of Parkinson's disease, they suggested.
Alistair Denniston, consultant ophthalmologist at University Hospitals Birmingham, and professor at the University of Birmingham, said the study findings demonstrated the "potential for eye data, harnessed by the technology to pick up signs and changes too subtle for humans to see". It was now possible to "detect very early signs" of PD, which could open up new treatment possibilities, he suggested.
The study did not have detailed clinical information about PD status in the patients, such as diagnosis date, treatment patterns, or current therapy, cautioned the authors, so they were not able to relate retinal changes to disease duration or progression. In addition, they recommended future studies to determine whether progression of GCIPL atrophy was driven by brain changes in PD, or whether INL thinning preceded GCIPL atrophy.
Dr Siegfried Wagner of UCL's Institute of Ophthalmology and Moorfields Eye Hospital, who led the investigation, expressed amazement at what could be discovered through eye scans. "While we are not yet ready to predict whether an individual will develop Parkinson's, we hope that this method could soon become a pre-screening tool for people at risk of disease," he said.
Dr Wagner added: "Finding signs of a number of diseases before symptoms emerge means that, in the future, people could have the time to make lifestyle changes to prevent some conditions arising, and clinicians could delay the onset and impact of life-changing neurodegenerative disorders."
Early Intervention "Key"
Asked to comment by Medscape UK News, Claire Bale, associate director of research at Parkinson's UK, stressed that "intervening earlier" to stop the loss of brain cells was the "key" to preventing the condition.
She echoed the hope that eye scans could be used to identify people at risk of developing Parkinson's disease to enable early treatment, and pointed out that because the eye scans analysed were non-invasive, and already in routine use, they could easily "be put into practice in the NHS".
The study was funded by Fight for Sight UK, the Medical Research Council, UK Research & Innovation, Basque Health Department, and the Wellcome Trust.