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In this concern, precise and high\u2010throughput molecular diagnosis and further pathologic insights are urgently needed. Here, through the combined strategy of nanoparticle\u2010enhanced laser desorption\/ionization mass spectrometry\u2010based rapid metabolic analysis (&lt;30\u00a0s) and machine learning, a precise molecular diagnostic approach of PM (HM with MMD grade \u2265 2) is proposed, which achieves areas under the curve of 0.874 and 0.889 for diagnosing PM and early\u2010stage PM, respectively. Further, the biomarkers indicate the PM\u2010associated systemic metabolic reprogramming of amino acid and lipid metabolism, which may mediate dysfunctional oxidative stress, inflammation, hormone\/neurotransmitter systems, and energy metabolism. Notably, MMD grade 4, featuring characteristic macula atrophy, exhibits specificity in this metabolic reprogramming. Of these biomarkers, azelaic acid shows a significant protective effect in the ARPE\u201019 cells under abnormal oxidative stress, which may be involved in PM development as a key antioxidative active metabolite. This work will contribute to PM molecular diagnosis and pathology exploration.<\/jats:p>","DOI":"10.1002\/advs.202505861","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T11:11:31Z","timestamp":1753441891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Plasma Metabolic Profile with Machine Learning Reveals Distinct Diagnostic and Biological Signatures for Pathologic Myopia"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5494-2613","authenticated-orcid":false,"given":"Ziheng","family":"Qi","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Engineering East China Normal University  Shanghai 200241 P. R. 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