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Last Updated: 09/01/2023

Predicting acute and post-recovery outcomes in cerebral malaria and other comas by Optical Coherence Tomography (OCT)

Objectives

To develop an OCT based bedside test to identify and quantify brain swelling in cerebral malaria (CM) and other comas, and predict neurodevelopmental deficit (NDD) in CM.

Specific objectives:

  1. To determine the accuracy of OCT measures of ONH swelling to detect severe brain swelling in children with CM compared to brain MRI.
  2. To ascertain the accuracy of OCT measures of macular ischaemia to predict NDD in children with CM at 1 and 2 years post-recovery.
  3. To establish if large accumulation of retinal haemorrhages predicts progression to severe brain swelling in children with CM.
  4. To determine if OCT measures of ONH swelling can detect and quantify raised ICP in other comas in children.
  5. To establish if a low-cost handheld OCT with AI analytics and tested to ISO standard can replace the commercially available OCT and human image analysis.

 

Principal Investigators / Focal Persons

Nicholas Beare
Karl Boynton Seydel

Rationale and Abstract

Children in Africa continue to die in large numbers from CM, mostly with severe brain swelling. New treatments for severe brain swelling and to reduce intracranial pressure (ICP) in CM are under clinical trial, but rely on MRI scans to identify severe brain swelling. Hardly any children with CM have access to MRI scanning, so those likely to benefit from new treatments are not identifiable. Children in coma for other causes would also benefit from the identification of raised intracranial pressure. Children who survive CM are at high risk of neurological and developmental complications. It is thought that this may be due to cerebral ischaemia but at present there is no method to identify these children other than waiting for their deficit to become manifest. Identifying CM patients at risk of neurological deficit or developmental delay would enable early intervention. Identifying a link between cerebral ischaemia and neurodevelopmental deficit (NDD) would also support the development of new treatments for CM which mitigate ischaemic injury. Optical Coherence Tomography (OCT) is a non-invasive ocular imaging modality which uses low-coherence light to obtain detailed cross-sectional images of the retina and optic nerve head (ONH). The ONH swells with raised intracranial pressure (papilloedema).

Study Design
  • Study design: Observational single-site cohort study with an acute phase and 1- to 2-year follow-up
  • Trial setting: Hospitals
  • Trial type: Diagnostic
Date

Jul 2021 — Apr 2026

Total Project Funding

$374,150

Funding Details
Wellcome Trust, United Kingdom

Grant number: 222530/Z/21/Z
£270,441
Project Site

Malawi

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