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Differentiating it from pseudopapilledema is often challenging and may require invasive investigations. Optical Coherence Tomography (OCT) is a non-invasive imaging modality, allowing visualisation of the ONH. We identified OCT-derived biomarkers for papilledema and pseudopapilledema in the existing literature. 213 patients with confirmed papilledema, optic disc drusen (ODD), tilted optic discs (TOD) or crowded optic discs (COD) were included. OCT scans were analysed for qualitative and quantitative biomarkers, with sensitivity, specificity, and AUC calculated for individual and combined biomarkers. Logistic regression modelling including qualitative biomarkers to differentiate papilledema from ODD and COD demonstrated a sensitivity and specificity of 89% and AUC of 0.96. Inclusion of TOD reduced the sensitivity of the model to 66%. In a model differentiating papilledema from TOD, the best-performing biomarker achieved a sensitivity of 87%, specificity of 61% and AUC of 0.83. Using qualitative biomarkers, we identified a model with high sensitivity and specificity to differentiate papilledema from ODD and COD. Quantitative biomarkers displayed high AUCs for differentiating TOD from papilledema. Our findings show that OCT demonstrates promising utility in differentiating papilledema from pseudopapilledema.<\/jats:p>","DOI":"10.1038\/s41598-025-09778-2","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:27:20Z","timestamp":1752139640000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identifying biomarkers for papilledema and pseudopapilledema"],"prefix":"10.1038","volume":"15","author":[{"given":"Rishi","family":"Sekhri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen J.","family":"Kuht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanhan","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail D. 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