A major goal of the study was to assess the methodologies available for the quantification of retinal lesions suitable for application in trials of metabolic management. We describe the methods used for grading stereoscopic color fundus photographs. Overall retinopathy severity level for each eye ranging from normal (level 10) to high-risk category (level 70) was assigned on the basis of gradings of individual lesions. Change in retinopathy severity level over the 8-mo period was detected in 3–62% of patients, depending on the method used and the definition of change. Lesions responsible for change in level were mainly retinal infarcts (soft exudates) and intraretinal microvascular abnormalities.