Diagnosing Parkinson’s disease (PD) can be challenging. Symptoms may begin 15 years before diagnosis.¹ But until enough symptoms that fit the criteria for diagnosis are present, no treatment will come. While many doctors wait to initiate treatment until symptoms progress, evidence shows the potential benefits of beginning treatments as early as possible.² However, identifying the signs of PD is a costly and potentially invasive imaging procedure.³ What if a simple scan of your eyes, like at the eye doctor, could predict PD diagnosis several years in advance? Let’s talk about it.

Three takeaways to tell your friends:

• Parkinson’s disease (PD) symptoms begin years before a diagnosis occurs.
• The back wall of the eye is called the retina, which consists of multiple layers of cells.
• Two layers of cells in the retina are thinner in PD patients, and each layer’s thickness can predict PD diagnosis several years in advance.⁴

If you have been to the eye doctor, you most likely have had an optical coherence tomography (OCT) scan. It is a perfectly safe way of visualizing the back wall of your eye, known as the retina. Within the retina are layers of cells that turn visual information into chemical signals. There are several layers, but the relevant ones to this study are the combined ganglion cell-inner plexiform layer (GCIPL) and the inner nuclear layer (INL). Now, you can disregard the complex and undefined terminology and instead recognize GCIPL and INL as layers of cells on the back wall of the eye (Figure 1). Under an OCT scan, the operator can see clear images of the layers of the retina and measure their thickness. It is a common technique for diagnosing eye diseases but never before for PD.

This study analyzed a database to prove retina thickness correlates with PD. In London, a recently created database contains hospital and eye records of patients, referred to as AlzEye.⁵ Using the Alzeye database, they collected data from 700 PD patients and 105,770 controls. They found that the PD patients were more likely male, older, and more likely to have hypertension and diabetes.⁴ Additionally, PD patients had vastly thinner GCIPL and INL than non-PD patients.⁴ To test if the effect was due to the diabetes patient’s data, as diabetes can affect vision, they removed the patients with diabetes and re-analyzed the data. Even without the diabetes patients, the remaining 344 PD patients had significantly thinner GCIPL and INL than non-PD patients.⁴ To summarize, PD correlates with thinner retina layers, specifically the GCIPL and INL.

If the thinning of GCIPL and INL precede PD’s diagnosis, then they could be used as a predictor of PD. Using data from the database of a long-term study, the UK Biobank, the researchers could examine eye scans from the past and align them to the patient’s current healthcare status (i.e., if and when they received a PD diagnosis). From the group, they examined 50,405 patients’ data. Of those, 53 became diagnosed with PD. The average time from eye scan to PD diagnosis was 4.9-9.6 years. So, the eye scans were taken years before PD diagnosis. What did the scans show, you ask? In future PD patients, the retina layers GCIPL and INL were significantly thinner than non-PD patients.⁴ Therefore, retinal layer thinning is a viable predictor of PD diagnosis years in advance.

In summary, early in the progression of PD, achieving a proper PD diagnosis is difficult. However, a noninvasive method of diagnosing PD several years in advance is here. We could begin treatment early,² do more research into early intervention therapies (now that we can diagnose in advance), and maybe just knowing what is coming can bring solace. Regardless, this is a leap for PD research.

REFERENCES

1.         Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson’s disease. Lancet Neurol. 2021;20(5):385-97.

2.         van den Heuvel L, Evers LJW, Meinders MJ, Post B, Stiggelbout AM, Heskes TM, et al. Estimating the Effect of Early Treatment Initiation in Parkinson’s Disease Using Observational Data. Mov Disord. 2021;36(2):407-14.

3.         Bidesi NSR, Vang Andersen I, Windhorst AD, Shalgunov V, Herth MM. The role of neuroimaging in Parkinson’s disease. J Neurochem. 2021;159(4):660-89.

4.         Wagner SK, Romero-Bascones D, Cortina-Borja M, Williamson DJ, Struyven RR, Zhou Y, et al. Retinal Optical Coherence Tomography Features Associated With Incident and Prevalent Parkinson Disease. Neurology. 2023;101(16):e1581-e93.

5.         Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, et al. AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353 157 patients in London, UK. BMJ Open. 2022;12(3):e058552.