Dopamine loss tied to retinal thinning; may be early disease biomarker
Retinal thinning was linked to dopaminergic neuronal atrophy in a cross-sectional analysis, raising the possibility that it could be a way to detect pathologic changes in early Parkinson's disease (PD) patients, researchers said.
Drug-naïve patients with early Parkinson's showed retinal thinning as measured by optical coherence tomography (OCT) that correlated with both disease severity and nigral dopaminergic degeneration, reported Jee-Young Lee, MD, PhD, of the Seoul National University Boramae Medical Center, and colleagues in Neurology.
"Our study is the first to show a link between the thinning of the retina and a known sign of the progression of the disease -- the loss of brain cells that produce dopamine," Lee said in a statement.
"We also found the thinner the retina, the greater the severity of disease. These discoveries may mean that neurologists may eventually be able to use a simple eye scan to detect Parkinson's disease in its earliest stages, before problems with movement begin."
Retinal pathology has been tied to other neurodegenerative disorders including dementia. In previous studies, retinal nerve fiber layer thickness has been linked to Parkinson's disease, and OCT is a potential PD biomarker.
The search for a definitive Parkinson's biomarker has been extensive and includes clinical (anosmia; REM behavior disorder), genetic (GBA mutation; LRRK2mutation), and biochemical (blood and cerebrospinal fluid) techniques, along with positron emission tomography (PET), magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT) imaging.
No biomarker has been validated for clinical practice, noted Jamie Adams, MD, of the University of Rochester Medical Center in New York, and Chiara La Morgia, MD, PhD, of the University of Bologna in Italy, in an accompanying editorial:
"Because of the complexity of the disease, combining biomarkers from different categories is likely the best strategy to accurately predict PD status and progression."
In this analysis, Lee and colleagues studied 49 Parkinson's patients with an average age of 69, along with 54 age-matched controls, including only early-stage, drug-naïve PD patients without ophthalmologic disease.
The researchers used high-resolution OCT to measure retinal nerve fiber layer thickness, microperimetry to measure retinal function, and dopamine transporter analysis to measure N(3-[18F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane uptake in the basal ganglia. Retinal layer thickness and volume were measured and compared in PD patients and controls.
Retinal thinning was found in the inferior and temporal perifoveal sectors of the PD patients, particularly the inner plexiform and ganglion cell layers, along with an association between retinal thinning and dopaminergic loss in the left substantia nigra. The team also reported an inverse association between inner retinal thickness in the inferior perifoveal sector and disease severity (Hoehn and Yahr stage), and a positive correlation between macular sensitivity and retinal layer thickness.
"Overall, these data support the presence of an association between retinal thinning and dopaminergic loss in PD," said Adams and La Morgia. "Inner retinal thinning in individuals with PD has been reported in previous studies, but this is the first study that demonstrates a correlation between inner retinal thinning and nigral dopaminergic loss."
"These findings may point to a pathologic connection between the retina and basal ganglia in PD and are in line with previous studies reporting asymmetric retinal nerve fiber layer loss, more evident in the eye contralateral to the most affected body side."
The results need to be interpreted with caution, Lee and co-authors noted. Retina analysis was limited to the macular area in this research. Studies with larger numbers of Parkinson's patients are needed to confirm the findings. And this study was a cross-sectional analysis, so correlations between retinal changes and PD severity need to be established over time.
But if the findings are confirmed, "retina scans may not only allow earlier treatment of Parkinson's disease, but more precise monitoring of treatments that could slow progression of the disease as well," Lee said.
The study was supported by the Seoul Metropolitan Government Seoul National University Boramae Medical Center and the Korean Ministry of Education, Science and Technology.
The researchers reported relationships with Samsung Bioepis and Retimark Inc.
The editorialists reported relationships with VisualDx, Azevan Pharmaceuticals, and Santhera Pharmaceuticals.
https://www.medpagetoday.com/neurology/parkinsonsdisease/74575
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