Proteomic and Clinical Characterization of Active vs. Quiescent Pterygium With Elevated Thrombospondin-1

Purpose: To investigate proteomic and clinical changes in active- and quiescent-stage pterygium and identify biomarkers. Methods: This study included 15 and 14 patients with quiescent- and active-stage pterygium, respectively. Clinical parameters (length, area, thickness, vessel density, and hemodynamics) were assessed using slit-lamp, anterior segment-optical coherence tomography angiography, and functional slit-lamp biomicroscopy. Label-free proteomics was performed on excised tissues. Thrombospondin-1 (THBS1) was validated via enzyme-linked immunosorbent assay, immunohistochemistry, and reverse transcription quantitative polymerase chain reaction. Correlation and receiver operating characteristic analyses were also conducted. Results: Compared with the quiescent stage, active pterygium exhibited significantly greater corneal invasion length, area, thickness, and vessel density, along with reduced vessel length. Proteomic analysis revealed 7 upregulated differentially expressed proteins whose pathways were mainly immune related and 15 downregulated differentially expressed proteins. THBS1 was significantly elevated in active tissue, confirmed by enzyme-linked immunosorbent assay, strong immunohistochemical staining, and higher messenger RNA levels. Receiver operating characteristic analysis supported THBS1 as a potential biomarker, yielding an area under the curve of 0.81 for distinguishing active-stage pterygium. Conclusions: Immune dysregulation and neovascularization may play an important role in pterygium progression. THBS1 may serve as a potential biomarker for predicting pterygium development and monitoring its progression. Translational Relevance: This work translates the discovery of elevated thrombospondin-1 into a potential clinical biomarker, bridging proteomic findings to the assessment of pterygium activity.