Abstract
Background: Macular neovascular disease is a group disorder with complex pathogenesis of neovascularization for vision impairment and irreversible blindness, posing great challenges to precise diagnosis and management. Methods: We conducted a cross-sectional association study to identify serum-based potential biomarkers of human macular neovascular disease. We prospectively recruited participants with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV) and pathological myopia (PM), compared with cataract patients without fundus diseases as control group. The serum metabolome was profiled by gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS) analysis. Multivariate statistical methods as well as machine learning were performed for interpretation of macular neovascularization. Findings: A total of 446 participants with macular neovascularization and 147 cataract subjects as control group were enrolled in this study. By employing GC-TOFMS, 131 metabolites were identified and 33 differentiating metabolites were highlighted in patients with macular neovascularization. Pathway analysis using lilikoi package in R language revealed pentose phosphate pathway and mitochondrial electron transport chain as the most important pathways in AMD; purine metabolism and glycolysis were identified as the major disturbed pathways in PCV while the altered thiamine metabolism and purine metabolism may contribute to PM phenotypes. Interpretation: In virtue of machine learning, the pathway-based model provides more personalized metabolic patterns for patient stratification of three subtypes of macular neovascular disease than metabolite-based model. Funding Statement: This work was supported by the grant from the National Key Research and Development Program of China (No. 2016YFC0904800) and the Interdisciplinary Program of Shanghai Jiao Tong University (No. YG2016MS82). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: [The authors] intended to conduct a prospective, observational, registration study. The Institutional Review Board (IRB) approval (No. 2016KY115-2) was obtained.
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