Optical coherence tomography reveals retinal structural abnormalities in α-synucleinopathies: insights from the Padua-CESNE cohort

The complexity of α-synucleinopathies, namely Parkinson's disease (PD) and multiple system atrophy (MSA), calls for the adoption a multimodal approach integrating biological, morphological, and functional data. Phosphorylated α-synuclein (α-syn) detection in bodily fluids and tissues such as the skin helps provide biological characterization of the disease, but specific and accessible biomarkers are not available yet. The aim of this study was to define the role of Optical Coherence Tomography (OCT, a minimally invasive retinal imaging technique) patterns as possible biomarkers in the early stages of α-synucleinopathies, also supporting the differential diagnosis. Thirty-five (23 PD, 12 MSA), clinically, biologically and genetically characterized patients included in the PADUA-CESNE (Centro Studi per la Neurodegenerazione) cohort underwent OCT. A significant atrophy in the inferior, superior and temporal regions of the Retinal Nerve Fiber Layer (RNFL) and in the inner nuclear layer (INL) were observed in PD compared to controls, differently from MSA. Hyperreflective foci (HRF) counts were elevated across all retinal layers in all patients with PD exhibiting significantly higher numbers, suggesting microglial activation and greater retinal damage. Further research regarding OCT patterns in PD and MSA may consolidate the role of specific features, such as INL abnormalities and different HRF counts, in supporting the diagnosis and differential diagnosis in α-synucleinopathies. In light of the availability of potentially disease-modifying therapies, studies should focus on newly diagnosed patients, also undergoing thorough clinical, biological and genetic characterization.