Diabetic macular edema (DME) is one of the most common and severe complications of diabetes, and it is a leading cause of blindness in the working-age population. The pathophysiology of DME is complex, resulting from the interplay of various factors. Controlling these risk factors is crucial in reducing the incidence of DME. As a systemic diseaserelated ocular condition, the onset and progression of DME are influenced by numerous risk factors. However, previous literature has provided insufficient summaries of these factors. This review aims to summarize the risk factors for DME from both systemic and ocular perspectives. The systemic risk factors primarily include poor glycemic control, prolonged duration of diabetes, hypertension, dyslipidemia, obesity, renal dysfunction, pregnancy, the use of hypoglycemic medications, anemia, obstructive sleep apnea-hypopnea syndrome, genetic factors, smoking, alcohol consumption, hypercalcemia, and hypomagnesemia. On the other hand, ocular risk factors include cataracts, glaucoma and vitrectomy, panretinal photocoagulation, coexisting retinal vein occlusion, and related cytokines. A deeper understanding of these risk factors will aid in the better prevention and early treatment of DME, while also providing guidance and reference for controlling the progression of DME during the treatment of diabetic retinopathy. However, some of these factors remain controversial, and additional DME risk factors still need to be explored. It is hoped that, in the near future, more
foundational and prospective clinical studies will provide high-quality evidence on DME risk factors and treatments.