Age-related macular degeneration (AMD) is an important cause of irreversible central blindness worldwide. Clinical manifestations range from asymptomatic in early and intermediate AMD to significant vision loss in late AMD. Approximately 10% of cases of early AMD eventually progress to the late advanced stage, influenced by the upregulation of vascular endothelial growth factor (VEGF). In this study, we evaluated VEGF concentration in the tears and serum of AMD patients. Our study revealed a significantly higher level of VEGF in the tears of patients with AMD compared with controls. The tear VEGF level has high sensitivity and specificity, and is significantly related to the severity of AMD, whilst serum VEGF level is non-specific and non-predictive of AMD severity. Thus, VEGF level in the tears may be used as a non-invasive biomarker for AMD progression. A large cohort study is needed for further verification.