In a study involving 97 patients with hemoglobin SC sickle cell disease (Hb SC) and 87 subjects with hemoglobin SS sickle cell disease (Hb SS) on the island of Curaçao, we found a higher incidence of peripheral retinal vascular closure and proliferative retinopathy in the former as compared with the latter. Examination of composite fluorescein angiograms obtained from 15 Hb SS and 36 Hb SC patients, whose mean and median age were the same and in whom more advanced stages of sickle retinopathy were equally represented, revealed statistically significantly smaller measurements of perfused retina (indicative of larger areas of non-perfusion) in Hb SC patients as compared with Hb SS patients (P = 0.002, P = 0.014) as well as in subjects exhibiting neovascularization as compared with those who did not (P = 0.022, P = 0.004). This suggests that a vaso-occlusive tendency in the retina is greater in individuals with Hb SC than in those with Hb SS; the more extensive ischemic areas provide a stimulus for neovascularization, explaining the higher prevalence of proliferative retinopathy in the former patients as compared with the latter.