A new neurology study provides compelling evidence that retinal imaging can detect Parkinson’s disease years before diagnosis.
Researchers found thinning of two inner retinal layers – the ganglion cell-inner plexiform layer (GCIPL) and inner nuclear layer (INL) – in people who went on to develop Parkinson’s disease up to 7 years later.
These findings suggest retinal screening could identify those at high risk of Parkinson’s, allowing earlier intervention to slow progression.
Key Facts:
- People who developed Parkinson’s disease had thinning of the GCIPL and INL layers on retinal imaging done years prior.
- GCIPL and INL thinning were also seen in those already diagnosed with Parkinson’s disease.
- The retina shows Parkinson’s-linked changes earlier than the brain, offering a window into early disease.
- Retinal screening could help identify high-risk individuals for clinical trials of new Parkinson’s treatments.
Source: Neurology. 2023 Aug 21.
What the Retina Reveals About Parkinson’s
The retina offers a unique window into the brain and neurodegeneration.
As an outpouching of the developing brain, it shares developmental pathways and cell types with the central nervous system.
Dopaminergic neurons – the cells damaged in Parkinson’s disease – are found in the inner nuclear layer (INL) of the retina.
Because the retina is more accessible than the brain, it provides a means to non-invasively detect neurodegenerative changes like those occurring in Parkinson’s disease.
Using advanced retinal imaging called optical coherence tomography (OCT), researchers can measure the thickness of retinal layers with near-micrometer precision.
Thinning of inner retinal layers indicates loss of neurons and their connections.
Prior Small Studies Hint at Retinal Changes
Previous small studies using OCT hinted at retinal changes in Parkinson’s disease, including thinning of the GCIPL layer. However, results were inconsistent, especially for the INL which harbors the dopamine neurons. Studies were also limited by excluding people with other conditions like diabetes.
Power of Big Data to Reveal Subtle Changes
To overcome limitations of small samples, researchers leveraged two large datasets – one containing over 150,000 patients who received retinal imaging and the other with over 50,000 people followed long-term in the UK Biobank.
The massive sample sizes enabled detection of small but consistent patterns.
Key Findings: Thinning of GCIPL and INL Precedes Diagnosis
In the first retrospective dataset, 700 people had a prior Parkinson’s diagnosis.
Compared to over 100,000 controls similar in age and sex, their GCIPL and INL layers were significantly thinner, by about 2 and 1 microns respectively.
Crucially, the prospective UK Biobank analysis followed thousands of initially healthy adults over time.
It found people who went on to develop Parkinson’s had thinner GCIPL and INL at baseline imaging, done 4-7 years prior to diagnosis.
GCIPL thinning was the most predictive marker.
A 1 standard deviation decrease in GCIPL thickness was associated with a 38% increased risk of developing Parkinson’s.
Insights into Parkinson’s Origins and Spread
Finding reduced thickness of both GCIPL and INL layers helps explain how Parkinson’s pathology arises and spreads in the brain and retina:
INL thinning likely reflects early loss of dopamine neurons in the retina itself.
GCIPL changes may result from retrograde degeneration spreading from the brain to the eye.
Combined INL and GCIPL thinning is consistent with a dual hit – both retinal dopamine loss and degeneration spreading from the brain.
Future screening focused on these two layers could identify individuals at high risk of Parkinson’s at a time when interventions may help slow its progression.
Wider Implications: Retinal Screening for Neurodegeneration
Beyond Parkinson’s disease, these findings demonstrate the power of “optometry” – using the eye to gain insight into neurological disease.
As the eye offers a window into the brain’s dopamine pathways, retinal changes likely reflect similar neurodegeneration unfolding in the brain itself.
Retinal screening and advanced OCT image analysis may enable early detection of other neurodegenerative diseases like Alzheimer’s.
Large, prospective studies in at-risk groups will help determine the predictive utility of retinal biomarkers.
In Parkinson’s disease, larger studies are still needed to define the timeline of retinal changes and their relationship with motor symptoms.
But the prospect of detecting pre-symptomatic disease through a quick, inexpensive eye scan is an exciting advance towards early intervention.
Study Methods and Design
This study combined data from two large cohorts with retinal imaging:
- AlzEye: Retrospective data from over 150,000 patients at eye hospitals in London, looking back at retinal scans in 700 people with a Parkinson’s diagnosis.
- UK Biobank: 50,000 healthy adults who had retinal imaging at enrollment and were followed for up to 7 years to track development of Parkinson’s disease.
Using advanced optical coherence tomography, the researchers measured thickness of the GCIPL and INL retinal layers in patients with Parkinson’s and controls.
They accounted for factors like age and diabetes when analyzing layer thickness.
Detecting Dopamine Loss in the Retina
Why would the INL show thinning in Parkinson’s disease?
This layer is full of neurons connecting to the overlying GCIPL and those harboring dopamine.
Parkinson’s is linked to dopamine neuron loss in the brain’s substantia nigra.
Similarly, autopsy studies show dopamine loss in the INL of Parkinson’s patients.
Finding reduced INL thickness on OCT imaging provides in vivo evidence of early dopamine loss in the retina.
When Retinal Changes Occur
A key question is when retinal changes emerge relative to Parkinson’s diagnosis.
The UK Biobank analysis detected GCIPL and INL thinning up to 7 years prior to Parkinson’s onset.
This suggests retinal imaging could identify high-risk individuals years before motor symptoms appear.
Early detection would aid clinical trial recruitment and allow timely intervention to slow disease progression.
However, larger studies are needed to definitively determine when retinal changes first emerge.
Tracking retinal layer thickness in those with prodromal markers like REM sleep behavior disorder will help establish a timeline.
Some possible limitations of this study
Limitations include reliance on hospital diagnosis codes to identify Parkinson’s rather than gold-standard clinical exams.
Not all controls were screened for pre-symptomatic Parkinson’s.
Additionally, the effects were small – on the order of 1-2 microns thinner layers in Parkinson’s. The predictive utility at the individual level remains to be determined.
Next steps include linking retinal changes to clinical features like Parkinson’s severity and progression.
Does more INL and GCIPL thinning equate to faster progression? Such associations would further validate retinal screening.
Studies also need to determine when retinal changes first emerge. Identifying those in early pre-symptomatic stages will be key for trials of disease-modifying therapies.
Major advance in Parkinson’s detection
This large dual cohort study provides compelling evidence that Parkinson’s disease can be detected through retinal thinning years before diagnosis.
Inner retinal layers, especially the GCIPL, show promise as predictive biomarkers to identify those at high risk and enable early intervention.
Further research is warranted to illuminate when retinal changes first emerge and how closely they track disease progression.
Nonetheless, this discovery of early retinal Parkinson’s fingerprints represents a major advance towards screening and secondary prevention.
References
- Study: Retinal Optical Coherence Tomography Features Associated with Incident and Prevalent Parkinson Disease
- Authors: Siegfried Karl Wagner et al. (2023)
