Measuring the Impact of Malaria on the Living Human Retina.

Retinal examination and imaging are relatively simple methods for studying the dynamic impact of cerebral malaria on the microcirculation of the central nervous system. Retina and brain are affected similarly by Plasmodium falciparum. Unlike the brain, the human retina can be directly observed using commercially available clinical instruments in the setting of a critical care unit, and this can be done repeatedly and non-invasively. Additional information about blood-tissue barriers can be gained from fluorescein angiography. Non-ophthalmologist clinician scientists are usually unfamiliar with ophthalmoscopy and retinal imaging, and some readers may feel that these techniques are beyond them. This chapter aims to quell these fears by providing a step-by-step description of how to examine and photograph the human retina in children with cerebral malaria.

Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina.

Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with P. falciparum cerebral malaria. We investigated their clinical significance and underlying mechanisms through linked clinical, clinicopathological and image analysis studies. Orange vessels and severe foveal whitening (clinical examination, n = 817, OR, 95% CI: 2.90, 1.96-4.30; 3.4, 1.8-6.3, both p<0.001), and arteriolar involvement by intravascular filling defects (angiographic image analysis, n = 260, 2.81, 1.17-6.72, p<0.02) were strongly associated with death. Orange vessels had dense sequestration of late stage parasitised red cells (histopathology, n = 29; sensitivity 0.97, specificity 0.89) involving 360° of the lumen circumference, with altered protein expression in blood-retinal barrier cells and marked loss/disruption of pericytes. Retinal whitening was topographically associated with tissue response to hypoxia. Severe neurovascular sequestration is visible at the bedside, and is a marker of severe disease useful for diagnosis and management.

Severity of retinopathy parallels the degree of parasite sequestration in the eyes and brains of malawian children with fatal cerebral malaria.

BACKGROUND: Malarial retinopathy (MR) has diagnostic and prognostic value in children with Plasmodium falciparum cerebral malaria (CM). A clinicopathological correlation between observed retinal changes during life and the degree of sequestration of parasitized red blood cells was investigated in ocular and cerebral vessels at autopsy. METHODS: In 18 Malawian children who died from clinically defined CM, we studied the intensity of sequestration and the maturity of sequestered parasites in the retina, in nonretinal ocular tissues, and in the brain. RESULTS: Five children with clinically defined CM during life had other causes of death identified at autopsy, no MR, and scanty intracerebral sequestration. Thirteen children had MR and died from CM. MR severity correlated with percentage of microvessels parasitized in the retina, brain, and nonretinal tissues with some neuroectodermal components (all P < .01). In moderate/severe MR cases (n = 8), vascular congestion was more intense (ρ = 0.841; P < .001), sequestered parasites were more mature, and the quantity of extraerythrocytic hemozoin was higher, compared with mild MR cases (n = 5). CONCLUSIONS: These data provide a histopathological basis for the known correlation between degrees of retinopathy and cerebral dysfunction in CM. In addition to being a valuable tool for clinical diagnosis, retinal observations give important information about neurovascular pathophysiology in pediatric CM.