Retinal Response Testing May Help Early Diagnosis of Parkinson’s Disease

A recent study has indicated that the retina of individuals with Parkinson’s disease responds differently to light than healthy individuals.1

Despite being the second most common neurodegenerative disease in the world, with a global prevalence of >6 million individuals, no effective treatment for Parkinson's disease has been found. A variety of potential risk factors have been connected to pathogenesis, such as age, genetics, and environmental and behavioral factors. However, Parkinson's disease is typically diagnosed after a patient consults a doctor for symptoms, including motor problems.2

“By then, the disease has been present for several years and the affected neurons are already engaged in an irreversible degenerative process,” said Martin Lévesque, professor at Université Laval’s Faculty of Medicine and researcher at CERVO Brain Research Center. “That’s why it’s important to find biomarkers that detect Parkinson’s at an early stage of the disease.”3

Previous studies have indicated that visual impairments, including impaired color discrimination, deficits in visual processing, and reduced contrast sensitivity, may be indicators of Parkinson's disease. These disorders tend to originate from dysfunction of the retina, which establishes electroretinography (ERG) as a hypothetically effective tool for detection.1

“To our knowledge, this is the earliest recorded instance of ERG anomalies in diagnosed Parkinson's disease patients, supporting the development of a diagnostic tool for early detection and monitoring, with the potential to improve interventions and patient management,” wrote Victoria Soto Linan, a doctoral student at Université Laval, and colleagues.1

ERG waveforms allow investigators to examine retinal cellular function; the a-wave reflects photoreceptor hyperpolarization in the outer retina, while the b-wave indicates inner retinal activity. Oscillatory potentials (OPs) along the ascending part of the b-wave likely arise from interactions between amacrine and bipolar cells, and the photopic negative response (PhNR) is linked to retinal ganglion cell (RGC) function, which represents the output of the retina.1

Linan and colleagues performed ERG with patients with idiopathic Parkinson's disease, with a mean age of 63.35 +/- 7.73, a mean disease duration of 4.15 +/- 2.06, and a mean H&Y score 2.07 +/- 0.59. In total, 20 patients with Parkinson's disease (n = 12 males, 8 females) were paired with 20 age-matched healthy controls (n = 9 males, 11 females).1

Cone and rod ERGs of each patient were explored. The photopic test consisted of a White-6500K flash stimulus (2.37-50.00 cd.s/m2) presented on an 80.00 cd/m2 White-6500K background. Two series of 20 flashes were delivered with a 2-second interval. RGC function in the PhNR test was determined using red flash luminance stimuli (4.49 cd.s/m2) on a rod-saturating blue 80.00 cd.s/m2 background, delivered as 2 series of 80 flashes with a 1-second interval.

For the scotopic test, a green flash luminance stimulus (.001-1.00 cd.s/m2) was presented after a 20-minute dark adaptation, with intensity ranges including lower (0.001-.001778 cd.s/m2), intermediate (.00316-.056 cd.s/m2), and higher (.1-1.00 cd.s/m2). Two series of 20 flashes were recorded for the lower intensities, two series of 10 for intermediate, and 15 flashes for higher. Interstimulus intervals were set at 2 seconds for .001-.1 cd.s/m2 stimuli and 5 seconds for .18-1 cd.s/m2 stimuli.1

ERGs of female patients exhibited impairment of scotopic b-wave and PhNR waveform, indicating an attenuated amacrine cell output. Overall results suggested reductions in the rod b-wave, scotopic OPs, PhNR b-wave, and PhNR-wave amplitudes in individuals with Parkinson's disease, which supports their potential as disease indicators.1

Ultimately, evidence pointed to reduced photopic b-wave, PhNR b-wave, and PhNR wave amplitudes, particularly in female patients with Parkinson's disease. Additionally, scotopic oscillatory potentials isolated further identified an attenuated amacrine cell output in females. Linan and colleagues believe that these results indicate promise in the effectiveness of ERG in early diagnosis and monitoring of Parkinson's disease.1

“In conclusion, our findings suggest that bipolar cell output is diminished in the rod and cone systems during early and advanced Parkinson's disease, respectively, with RGCs ultimately transmitting attenuated signals through the optic nerve,” Linan and colleagues wrote. “These early changes contrast with more advanced impairments in later-stage Parkinson's disease, and provide a novel early characterization.”1

References

1. Soto Linan V, Rioux V, Peralta M, Dupré N, Hébert M, Lévesque M. Early detection of parkinson’s disease: Retinal functional impairments as potential biomarkers. Neurobiology of Disease. 2025;208:106872. doi:10.1016/j.nbd.2025.106872

2. Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson's disease. Lancet Neurol. 2021;20(5):385-397. doi:10.1016/S1474-4422(21)00030-2

3. Neurobiology of Disease. Detecting Parkinson’s disease with a simple retinal exam. Eurekalert! May 1, 2025. Accessed May 1, 2025. https://www.eurekalert.org/news-releases/1082383