Abstract
INTRODUCTION: Atrophic myopic maculopathy (AMM) causes irreversible and progressive visual impairment. Metabolomics offers a valuable opportunity for exploring the pathological mechanisms of AMM and identifying potential therapeutic targets. This study compared serum metabolite profiles between patients with high myopia with and without AMM. METHODS: This case-control study included 57 adults with high myopia (30 with AMM, 27 without AMM). Clinical data including body mass index (BMI), fasting blood glucose, and lipid profiles were recorded. Serum samples were analyzed using untargeted metabolomics based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Differential metabolites were first screened for their discriminative performance using receiver operating characteristic (ROC) curves. Weighted gene co-expression network analysis (WGCNA) was then applied to explore co-expression patterns and identify metabolite modules associated with clinical traits. Multivariate logistic regression was performed to identify independent metabolic predictors of AMM. RESULTS: Compared with controls, patients with AMM showed significant alterations in serum metabolites, including 18 upregulated and 26 downregulated compounds, enriched in 5 pathways. WGCNA and ROC analysis identified 11 potential biomarkers associated with atrophy grades in AMM. Three metabolites were independently associated with AMM after adjustment: triglyceride (OR = 2.73, p = 0.021), ln[Tetracosahexaenoic acid] (OR = 3.54, p = 0.004), and ln[Decanoylcarnitine] (OR = 0.37, p = 0.025). The model showed good fit (χ² = 22.89, p < 0.001) with 71.9% accuracy and AUC = 0.821 (95% CI: 0.715-0.927). CONCLUSIONS: This study provides exploratory evidence of dysregulated serum fatty acid metabolism in AMM. These findings suggest that such metabolic alterations may be associated with mitochondrial dysfunction and inflammatory processes, offering a potential direction for future mechanistic and therapeutic research.