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Objectives To relate retinal findings in children treated for severe malaria to disease outcome and to determine the course of changes in the fundus. Methods A prospective study of children with cerebral malaria (CM) and severe malarial anemia admitted to the Malaria Research Project, Blantyre, Malawi, during 2 malaria seasons. Indirect and direct ophthalmoscopy were performed on admission and daily, subject to the patient's cooperation. Results Three hundred twenty-six patients (91%) with complicated malaria were recruited. Two hundred seventy-eight patients had CM and of these 170 (61%) had some degree of retinopathy; 25 (53%) of 47 with severe malarial anemia had retinopathy. In CM, retinopathy was associated with subsequent death (relative risk, 3.7; 95% confidence interval, 1.6-8.5) and papilledema conferred the highest risk (relative risk, 4.5; 95% confidence interval, 2.7-7.6). Increasing severity of retinal signs was related to increasing risk of a fatal outcome (P<.05), independent of papilledema. In survivors, retinal signs were associated with prolonged time to recover consciousness (P<.001). Patients with severe malarial anemia had better outcomes and less severe retinopathy than those with CM. In 116 patients with CM, fundi were followed up longitudinally during admission and in 27 patients after hospital discharge. A large increase in retinal hemorrhages was associated with death (P = .02). Retinal signs resolved over 1 to 4 weeks without retinal sequelae. Conclusions In childhood CM, severity of retinopathy is related to prolonged coma and death. Our results support the hypothesis that retinal signs in CM are related to cerebral pathophysiology. [ABSTRACT FROM AUTHOR]