VEGFA and Hyperglycemia: The underlying mechanism is as follows: hyperglycemia first induces hypoxia-ischemia and further leads to the over-expression of vascular endothelial growth factor (VEGF) (36, 37), i.e., a hypoxia-inducible cytokine to promote neovascularization (38–40), neo-vessels then branch off from pre-existing branch vessels, bend slowly and even cluster in balls (tufts), leading to elevated tortuosity of branch vessels (41), thus the increased tortuosity of branch retinal vessels may signal pathogenic neovascularization induced by hyperglycemia.