Diabetes is the most common cause of cotton-wool spots. The presence of more than eight cotton-wool spots has been associated with a higher risk of the more severe form of diabetic retinopathy known as proliferative diabetic retinopathy (PDR).
Cotton-wool spots are also a common sign of infection with the human immunodeficiency virus (HIV). They are present in more than half of the people with full-blown AIDS. Their presence can be an important sign of the severity of HIV-related disease.