Prophylactic photocoagulation may have a role in the treatment of proliferative sickle retinopathy in selected patients with SC disease, but none of the studies reported to date have established that such treatment of these eyes improves the long-term visual outcome as compared with the natural history as documented in this study. The similar visual outcomes in the eyes reviewed in this natural history study as compared with those that have been treated with photocoagulation should not be unexpected, because there is greater predilection for spontaneous involution or autoinfarction of the neovascular tissue in SC disease as opposed to the neovascularization that develops in other retinal vascular disease. A controlled, multicenter clinical trial designed to study those eyes at greatest risk should be considered. Such a trial should specify patient age (15 to 30 years), hemoglobin type (SC disease), and a minimum threshold of active proliferative disease (60 degrees or greater). Such criteria have been suggested by others. By comparing the outcome of eligible eyes randomly assigned to treatment or observation and followed for an extended period, it will be possible to learn whether laser photocoagulation offers a better prognosis than the natural history of proliferative sickle retinopathy. There is no question that in some eyes with proliferative sickle retinopathy, nonclearing vitreous hemorrhage and/or retinal detachment will develop. Clear definition of the risk factors leading to these advanced stages, however, is lacking, and the value of treatment is uncertain.