Metabolomics analysis between HEs present and absent in patients with PDR. (A) PCA score plot showed no trend of separation. (B) PLS-DA score plot indicated clear separation. (C) Permutation test of PLS-DA model. There was no over-fitting. (D) Top 15 metabolites ranked by VIP values of PLS-DA model. (E) KEGG pathway enrichment analysis of 19 differential metabolites. Abbreviations: DR, diabetic retinopathy; HEs, hard exudates; KEGG, Kyoto Encyclopedia of Genes and Genomes; NPDR, non-proliferative retinopathy; PCA, principal component analysis; PDR, proliferative retinopathy; PLS-DA, partial least squares-discriminant analysis.