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Simon P Harding, Ian J MacCormick, Simon Glover, Macpherson Mallewa, Terrie Taylor, Malcolm E Molyneux; Retinal Vascular Leakage is Associated with Death in Cerebral Malaria in African Children. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2190.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the presence and severity of leakage from the retinal neurovasculature in pediatric cerebral malaria (CM) and relate it to death and neurological disability.
We performed fluorescein angiography in the pediatric research ward in Blantyre, Malawi, on children admitted between 2006-2010 who met a clinical definition of CM (acute onset coma (Blantyre Score ≤2) in presence of P Falciparum without other identifiable cause of altered consciousness). Images were graded for the presence and severity of leakage subtypes by a single observer masked to outcome. Data (left eye) were compared to outcome (death, survival without disability) using multivariate analyses.
Data on 158 cases were available. Three subtypes of fluorescein leakage were identified which varied in severity, could occur in multiple regions, and could coexist with other subtypes. Images were not gradable for all subtypes in a small number of cases. Vessel segment leak was common (102/155 (65.8%)) and seen in larger venules, post-capillary venules and capillaries - only one case had leakage from arterioles. Focal leakage (21/156 (13.5%)) involved areas of 100-500μm in greatest linear diameter and occasionally occurred in large numbers, up to 15 per eye. Serial images during admission suggested this is an initial phase of hemorrhage development. Punctate multifocal leak (21/155 (13.5%)) comprised significant dye leakage through very small segments of capillaries, and was often widespread. It did not appear to precede hemorrhage. After controlling for other confounders on admission, death was significantly associated with focal (OR (95%CI) 2.48 (1.39-4.44) p<0.01) and punctuate multifocal leak (OR (95%CI) 2.45 (1.36-4.41), p<0.01) but not with presence or severity of vessel segment leak (OR 1.26 (0.84-1.9), p>0.2). Severity of vessel segment leak was associated with younger age (OR 0.6 (0.49-0.76), p<0.001) and co-existent severe malarial anaemia (OR 1.6 (1.1-2.4), p<0.01).
Pediatric CM frequently involves distinct patterns of retinal neurovascular leakage, with a wide range of severity. Leakage from postcapillary venules is common and is more likely in younger children. Focal leakage subtypes are strongly associated with death. Damage to the blood retina barrier may reflect similar pathogenesis in the brain.
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