Cerebral malaria: insight into pathology from optical coherence tomography

Abstract

We aimed to investigate structural retinal changes in malarial retinopathy (MR) using hand-held optical coherence tomography (HH-OCT) to assess its diagnostic potential. Children with MR (n = 43) underwent ophthalmoscopy, fluorescein angiography and HH-OCT during admission, 1-month (n = 31) and 1-year (n = 8) post-discharge. Controls were comatose patients without malaria (n = 6) and age/sex-matched healthy children (n = 43). OCT changes and retinal layer thicknesses were compared. On HH-OCT, hyper-reflective areas (HRAs) were seen in the inner retina of 81% of MR patients, corresponding to ischaemic retinal whitening on fundus photography. Cotton wool spots were present in 37% and abnormal hyper-reflective dots, co-localized to capillary plexus, in 93%. Hyper-reflective vessel walls were present in 84%, and intra-retinal cysts in 9%. Vascular changes and cysts resolved within 48 h. HRAs developed into retinal thinning at 1 month (p = 0.027) which was more pronounced after 1 year (p = 0.009). Ischaemic retinal whitening is located within inner retinal layers, distinguishing it from cotton wool spots. Vascular hyper-reflectivity may represent the sequestration of parasitized erythrocytes in vessels, a key CM feature. The mechanisms of post-ischemic retinal atrophy and cerebral atrophy with cognitive impairment may be similar in CM survivors. HH-OCT has the potential for monitoring patients, treatment response and predicting neurological deficits.

Retinal Imaging Technologies in Cerebral Malaria: A Systematic Review

“…The presence of hyperre ective vessels and hyperre ective capillaries in the inner retinal layers is unique to CM. This provides another potential example of in-vivo visualisation of sequestered pRBCs 29 . However, it is not yet known how hyperre ectivity of vessels relates to visible vessel abnormalities and their histopathological correlates.…”

“…OCT facilitates the detection of subtle and sub-clinical macular oedema and other changes to retinal integrity, as well as helping to differentiate causes of optic nerve head swelling. We identi ed only one paper describing changes on OCT in human CM 29 . A further study uses the technology in a murine model of CM 30 .…”

“…A further study uses the technology in a murine model of CM 30 . 4) 29 . Firstly, they identi ed hyperre ective areas (HRAs) affecting the inner retinal layers which, when large, colocalise to areas of retinal whitening and CNP on fundus photography and FA, respectively.…”

“…Cotton wool spots were visible in the retinal nerve bre layer (RNFL) as raised and well-de ned lesions with lower signal density when compared to HRAs 29 . They were much more common on OCT than have previously been appreciated clinically (37 vs. 5%), suggesting clinical misclassi cation as retinal whitening 18,29 . Cotton wool spots are caused by axonal injury in the RNFL, often secondary to ischaemia.…”

Identifying effective diagnostic biomarkers for childhood cerebral malaria in Africa integrating coexpression analysis with machine learning algorithm

“…Cerebral malaria (CM), a neurological complication caused by malaria, is one of the most serious neurological disease in the world, with a high mortality rate, and is the primary cause of malaria death [ 1 ]. The onset age of CM mainly occurs in children aged 40–45 months, and children under five years of age account for 67% of all malaria deaths [ 2 ].…”