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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 \u03b1-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 \u03b1-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.<\/jats:p>","DOI":"10.1007\/s00702-025-02918-y","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T13:33:24Z","timestamp":1744724004000},"page":"1013-1022","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Optical coherence tomography reveals retinal structural abnormalities in \u03b1-synucleinopathies: insights from the Padua-CESNE cohort"],"prefix":"10.1007","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-7168","authenticated-orcid":false,"given":"M.","family":"Campagnolo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Puthenparampil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Emmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Weis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Basili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Mauceri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Miscioscia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Carecchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Misenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Fogliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Antonini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"2918_CR1","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1007\/s00415-016-8230-0","volume":"263","author":"J Ahn","year":"2016","unstructured":"Ahn J, Lee JY, Kim TW (2016) Retinal thinning correlates with clinical severity in multiple system atrophy. 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AA has received compensation for consultancy and speaker related activities from UCB, Bayer, Ever Pharma, Britannia, AbbVie, Zambon, Bial, Theravance Biopharma, Jazz Pharmaceuticals, Roche, Medscape; he receives research support from Horizon 2020, Italian Ministry of University and Research (MUR), Italian Ministry of Health, Next Generation EU\u2014National Center for Gene Therapy and Drugs based on RNA Technology and National Recovery and Resilience Plan, Investment PE8 \u2013 Project Age-It: \u201cAgeing Well in an Ageing Society\u201d.MC has received travel grants from Zambon and receives support from Progetto di ricerca di Rilevante Interesse Nazionale \u2013 PRIN 2022 FJAXY8. All the other authors have no financial disclosure to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Written informed consent was obtained from each participant after a detailed description of the study. Informed consent for the use of biological samples was obtained from all patients. All procedures on human tissue samples were carried out in accordance with the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}