Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of vision loss globally, affecting approximately one-third of the 285 million people with diabetes. Hyperglycemia and hypertension are established risk factors for DR, and their control has been shown to prevent onset and progression. Recent research has identified novel risk factors, including inflammation, oxidative stress, and genetic variations, which have improved understanding of the biological pathways involved in DR and DME. This review explores major trends in the prevalence, incidence, progression, and regression of DR and DME, highlighting regional differences and gaps in the literature. Established and novel risk factors are extensively reviewed, with a focus on landmark studies and recent updates. The review also discusses the impact of duration of diabetes, puberty, pregnancy, obesity, and other modifiable and non-modifiable factors on the development and progression of DR and DME. Additionally, it examines the role of metabolic hormones, oxidative stress, vitamin D, and genetic factors in the pathogenesis of these conditions.Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of vision loss globally, affecting approximately one-third of the 285 million people with diabetes. Hyperglycemia and hypertension are established risk factors for DR, and their control has been shown to prevent onset and progression. Recent research has identified novel risk factors, including inflammation, oxidative stress, and genetic variations, which have improved understanding of the biological pathways involved in DR and DME. This review explores major trends in the prevalence, incidence, progression, and regression of DR and DME, highlighting regional differences and gaps in the literature. Established and novel risk factors are extensively reviewed, with a focus on landmark studies and recent updates. The review also discusses the impact of duration of diabetes, puberty, pregnancy, obesity, and other modifiable and non-modifiable factors on the development and progression of DR and DME. Additionally, it examines the role of metabolic hormones, oxidative stress, vitamin D, and genetic factors in the pathogenesis of these conditions.