Window to health: ocular imaging for chronic and systemic disease assessment

Chronic and systemic health conditions frequently suffer from a lack of convenient, non-invasive diagnostic tests and imaging instruments, resulting in missed opportunities to detect illnesses early and causing increased patient suffering, missed opportunities for early intervention, worse outcomes, and increased costs. The eye offers unique insight into several chronic and systemic conditions.

Blood vessels in the retina are shared with brain blood vessels, and when blood vessels in the brain experience disruption, this is often associated with retinal blood vessel disruption (e.g. malarial retinopathy in cerebral malaria). Protective barriers (the blood-brain and blood-retina barriers) in the smallest blood vessels prevent large molecules and pathogens such as viruses passing from blood into the retina and brain, and the breakdown of these barriers can lead to a range of chronic ocular and neurodegenerative conditions.

Understanding what is happening in the eye can therefore tell us what is happening in the brain. Imaging of the eye is already routinely practiced, and can be conducted quickly and non-invasively, but this is currently targeted primarily at understanding the health of the retina by looking at changes in retinal structure, rather than being used to understand the brain or detecting molecular and blood flow changes.

I will develop state-of-the-art retinal imaging systems and techniques to detect retinal indicators of chronic and systemic conditions.

I will build a fluorescence lifetime imaging ophthalmoscope, to detect molecular spectral signatures and detect the presence of biomarkers across the retina. This system will use state-of-the-art single-photon detector arrays from the University of Edinburgh to achieve the most thorough assessment of retinal molecular composition ever. This system will then be used to investigate two key conditions, Alzheimer's disease and diabetic retinopathy.

In the first stage of this fellowship, I will collaborate with clinical partners as part of existing research programmes to obtain preliminary evidence of molecular signatures of disease, which will be used to pursue larger clinical research projects in the second stage of this fellowship. This research programme builds on the scanning confocal and fluorescence imaging techniques already developed by Occuity that target the lens.

Potential commercialisation of this system will be built on a diverse long-term collaboration between multiple industry and academic partners developed in this second stage.

I will also develop a laser speckle contrast imaging system to assess retinal microvascular blood flow. Although laser speckle contrast imaging has already been used to assess retinal blood flow in large blood vessels, microvascular changes are far more relevant for conditions such as diabetic retinopathy and septic shock. Combining emerging multiple-exposure speckle imaging techniques with image stabilisation techniques pioneered by Occuity and utilising advances in camera technology, quantitative microvascular flow measurements will be demonstrated and validated through comparisons to existing methods such as optical coherence tomography angiography and fundus fluorescein angiography that are either invasive or prohibitively slow.

Collaborating with clinical partners with existing research programmes, I will then demonstrate the potential usefulness of the system investigating septic shock and diabetic retinopathy and generate the preliminary evidence necessary to establish larger clinical research projects in the second stage of this project. I will also develop a commercial prototype during the first stage of this project, supported by a market assessment and commercialisation case study, setting the ground for market translation in the second stage of this fellowship.