Abstract
Purpose :
Cerebral malaria is an infectious disease with high mortality and inadequate diagnosis prior to death. The retina is an optically accessible neural tissue in which changes to blood vessels and hemorrhage match the changes seen in the brain in cerebral malaria. We and others have previously reported the imaging of hemozoin in retinal vessels. Here we report the presence of amyloid beta (Aβ) spherulites (deposits) previously found in conditions associated with neuronal injury (e.g., in traumatic brain injury).
Methods :
One retina from each of two subjects with a diagnosis of death due to cerebral malaria and two who died from coma due to other causes were flat mounted. Hemozoin deposits and Aβ spherulites deposits were detected in the quarter section of the retinas using a microscope modified with a polarimeter to image with polarised light. The presence of hemozoin and Aβ spherulites was then compared to the diagnosis of cerebral malaria based on brain pathology.
Results :
Fields were imaged that contained only hemozoin, only spherulite deposits, and both hemozoin in blood vessels and spherulites in tissue. Malaria negative brain pathology correlated with no evidence of hemozoin or spherulites in the retina. Malaria positive brain pathology correlated with both hemozoin and spherulites in the retina. The spherulites displayed the Maltese cross under crossed polarized light and birefringence which is characteristic of Aβ. Aβ spherulites have previously been reported in other conditions, but not to our knowledge in cerebral malaria. The deposits could be differentiated from the surrounding retina by their optical retardance, its fast axis orientation, and other interactions with polarised light. The morphology of the spherulites found is similar to some reports in the brain of those with Alzheimer’s disease (AD), but differed from the morphology of amyloid deposits that we have found previously in retinas of those with AD.
Conclusions :
The hemozoin clumps and presumed Aβ spherulites in the retina were large enough to be resolved in vivo without the use of adaptive optics. In vivo retinal imaging is a promising non-invasive tool for improving the diagnosis of cerebral malaria with hemozoin as a marker of malaria and presumed Aβ spherulites as potential markers of retinal damage from cerebral malaria.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.