Elevated α-synuclein and NfL levels in tear fluids and decreased retinal microvascular densities in patients with Parkinson's disease

The pathognomonic hallmark of Parkinson's disease (PD), alpha-synuclein, has been observed in the retina of PD patients. We investigated whether biomarkers in the tears and retinal microvascular changes associate with PD risk and progression. This prospective study enrolled 49 PD patients and 45 age-matched healthy controls. The alpha-synuclein and neurofilament light chain (NfL) levels were measured using an electrochemiluminescence immunoassay. Retinal vessel density was assessed using optical coherence tomography angiography (OCT-A). The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Mini-Mental State Examination score were used to assess motor and cognitive progression. The alpha-synuclein and NfL levels in the tears were higher in PD patients than in controls (alpha-synuclein: 55.49 +/- 8.12 pg/mL vs. 31.71 +/- 3.25 pg/mL, P = 0.009; NfL: 2.89 +/- 0.52 pg/mL vs. 1.47 +/- 0.23 pg/mL, P = 0.02). The vessel densities in the deep plexus of central macula and the radial peripapillary capillary layer of disc region were lower in PD patients with moderate-stage compared with early-stage PD (P < 0.05). The accuracy of predicting PD occurrence using age and sex alone (area under the curve [AUC] 0.612) was significantly improved by adding alpha-synuclein and NfL levels and retinal vascular densities (AUC 0.752, P= 0.001). After a mean follow-up of 1.5 +/- 0.3 years, the accuracy of predicting motor or cognitive progression using age, sex, and baseline motor severity as a basic model was increased by incorporating retinal microvascular and biofluid markers as a full model (P = 0.001). Our results showed that retinal microvascular densities combined with alpha-synuclein and NfL levels in tears are associated with risk and progression of PD.