Systemic risk factors contribute differently to the development of proliferative diabetic retinopathy and clinically significant macular oedema

Aims/hypothesis The purpose of screening for diabetic retinopathy is to detect either of the two sight-threatening complications: proliferative diabetic retinopathy (PDR) or clinically significant diabetic macular oedema (DME). The aim of the study was to evaluate whether systemic risk factors affect the risk of developing these two complications differently. Methods Survival analysis with death as a competing risk was used to describe the effect of sex, age and time of onset of diabetes, systolic (SBP) and diastolic (DBP) BPs, and the weighted exposure and CV of HbA(1c) for the development of PDR and DME from all 2773 patients treated for diabetic retinopathy in a defined population from the Aarhus area, Denmark, between 1 July 1994 and 1 July 2019. Results Increasing HbA(1c) above normal increased the risk of developing both PDR and DME (p < 0.04), and values below normal increased the risk of developing PDR (p < 0.013). Increasing DBP increased the risk of developing both PDR and DME (p < 0.0001), whereas increasing SBP increased the risk of developing DME (p < 0.0001), but not PDR (p > 0.08). The risk of developing PDR increased with decreasing age of onset of diabetes (p < 0.0001), whereas the risk of developing DME was maximal for a known onset of diabetes at about 30 years of age and decreased significantly for both lower and higher ages of onset (p < 0.0001). The risk of developing both PDR and DME was lower in women than in men (p < 0.004) and was reduced with lower variability of repeated HbA(1c) measurements (p < 0.0001). Conclusions/interpretation Systemic risk factors such as metabolic regulation, arterial BP and the age of onset of diabetes contribute differently to the development of PDR and DME. The overall risk of developing treatment-requiring diabetic retinopathy should be calculated from the risks of reaching each of the two complications separately.