Abstract
Diabetic retinopathy (DR) is a leading cause of vision impairment worldwide, necessitating early detection and personalized treatment strategies. Liquid biopsy, a minimally invasive diagnostic tool, offers significant advantages over traditional methods by enabling analysis of biofluids such as blood, tears, aqueous humor, and vitreous humor. This review highlights the advances in liquid biopsy techniques, sample collection methods and their applications in protein detection and metabolomics analysis for DR. It also explores the key protein biomarkers, including vascular endothelial growth factor (VEGF), inflammatory cytokines, and matrix metalloproteinases (MMPs), and investigates the associations between different biofluids. Metabolomics of liquid biopsy is emphasized for its role in identifying metabolic biomarkers linked to DR pathogenesis, providing new insights into disease mechanisms and personalized interventions. The challenges of liquid biopsy, such as technical limitations and the need for standardization, are also discussed. Advances in computational tools, bioinformatics, and artificial intelligence are supposed to further enhance multi-omics integration, thereby improving precision medicine in DR care. This comprehensive review brings attention to the transformative potential of liquid biopsy in DR diagnosis and management, with implications for broader ophthalmic and systemic diseases.