Underlying cause of diabetic retinopathy: Metabolic instability

Although diabetic retinopathy is still a major contributor to avoidable visual impairment, its pathophysiology is frequently only considered in relation to chronic hyperglycemia. This rigid viewpoint is challenged by new data that highlight the pathogenic importance of transient metabolic instability. Retinal endothelial cells, pericyte viability, and neuroglial equilibrium appear to be independently influenced by rapid glucose fluctuations, variability in fasting glucose, and transient metabolic stress, which accelerates microvascular and neurodegenerative injury. These results suggest that dynamic metabolic instability is associated with increased retinal vulnerability and may contribute to microvascular and neurodegenerative injury. Despite growing interest, the lack of validated thresholds for harmful glycemic volatility, inconsistent variability metrics, and diverse study methodologies limits clinical translation. To identify early neurovascular dysfunction, future research should integrate continuous glucose monitoring parameters with retinal imaging biomarkers. Adopting a dynamic metabolic framework may improve risk assessment, enable tailored screening plans, and ultimately advance the prevention and treatment of diabetic retinopathy.