PREDICTOR - PRE-symptomatic DIagnosis through adaptive optiCal Tomographic sensing Of the Retina
Lead Research Organisation:
UNIVERSITY OF OXFORD
Department Name: Engineering Science
Abstract
Medical imaging techniques such as MRI have revolutionised clinical diagnosis, treatment and monitoring of disease. However, they are expensive and not readily accessible outside specialist units. Imagine if instead, there was available a high-street eye test that provided diagnostic information for a range of diseases. These diseases could be neurodegenerative diseases such as Alzheimer's, systemic diseases (diseases with wide-spread effect on the body) such as heart disease, or psychiatric conditions, such as depression. The test would be sensitive, picking-up signatures of disease before any symptoms were apparent and before irreparable damage had occurred, and allowing fine scale monitoring of changes in response to treatment. It would offer specificity, differentiating between diseases with different aetiologies but similar retinal manifestations. This would allow mechanistic understanding of disease progression, paving the way for future therapies.
The key to realising this vision is the application of recent technological advances from microscopy, image and signal processing to high-resolution optical imaging of the living human retina. The retina, which is the tissue at the back of our eye, is in fact a part of the central nervous system and has long been recognised as a window to the brain and vasculature. In fact, psychiatric, neurodegenerative, and systemic diseases have been shown to have detectable correlates in the eye. However, current clinical technology cannot image individual cells, and so these diseases manifest in gross anatomical changes that cannot be distinguished amongst diseases. We will develop a non-invasive optical instrument, capable of imaging individual cells and testing their function, for sensitive and specific detection of these diseases. The technology would revolutionise point-of-care medicine by providing rapid, non-invasive diagnostics on a range of conditions, replacing costly, time-consuming current gold standard methods.
Our team is a collaboration between technology developers and ophthalmic specialists, spanning engineering and medical science within partner institutions. We already have experience in human participant testing across the life-span with bespoke optical instrumentation, and extensive experience in commercialisation of technology, industrial partnership and spin-outs. The required technological components - for example, optical interferometry, adaptive optics, spectroscopic and polarisation techniques, holography, and dedicated image and signal processing - are available in the related fields of microscopy and ophthalmoscopy, but delivering an integrated instrumentation package remains a significant engineering challenge. The development phase will be vital for establishing proof-of-principle demonstrations to engage stakeholders, and to target efforts to those areas that are most likely to have 'disruptive' impact in healthcare. Stakeholders - clinicians, industry partners and patient groups - will be engaged through local NHS Trusts and teaching hospitals, existing industry networks and charities representing specific patient cohorts. During the development phase we will widen and deepen these networks. With a long-term view, we will engage at all levels of medical training - from the pre-clinical undergraduate to the established consultant.
Three significant challenges facing society are the high incidence of mental health issues across the population, cardiovascular disease, and neurodegenerative diseases which disproportionately affect the elderly and are of great concern in an ageing society. Dementia and heart disease are the leading causes of death in the UK, and indeed world-wide. Faster and more effective diagnosis and treatment of such debilitating conditions will significantly improve outcomes for these patients. Widespread uptake of the technology will lead to new business growth through commercialisation.
The key to realising this vision is the application of recent technological advances from microscopy, image and signal processing to high-resolution optical imaging of the living human retina. The retina, which is the tissue at the back of our eye, is in fact a part of the central nervous system and has long been recognised as a window to the brain and vasculature. In fact, psychiatric, neurodegenerative, and systemic diseases have been shown to have detectable correlates in the eye. However, current clinical technology cannot image individual cells, and so these diseases manifest in gross anatomical changes that cannot be distinguished amongst diseases. We will develop a non-invasive optical instrument, capable of imaging individual cells and testing their function, for sensitive and specific detection of these diseases. The technology would revolutionise point-of-care medicine by providing rapid, non-invasive diagnostics on a range of conditions, replacing costly, time-consuming current gold standard methods.
Our team is a collaboration between technology developers and ophthalmic specialists, spanning engineering and medical science within partner institutions. We already have experience in human participant testing across the life-span with bespoke optical instrumentation, and extensive experience in commercialisation of technology, industrial partnership and spin-outs. The required technological components - for example, optical interferometry, adaptive optics, spectroscopic and polarisation techniques, holography, and dedicated image and signal processing - are available in the related fields of microscopy and ophthalmoscopy, but delivering an integrated instrumentation package remains a significant engineering challenge. The development phase will be vital for establishing proof-of-principle demonstrations to engage stakeholders, and to target efforts to those areas that are most likely to have 'disruptive' impact in healthcare. Stakeholders - clinicians, industry partners and patient groups - will be engaged through local NHS Trusts and teaching hospitals, existing industry networks and charities representing specific patient cohorts. During the development phase we will widen and deepen these networks. With a long-term view, we will engage at all levels of medical training - from the pre-clinical undergraduate to the established consultant.
Three significant challenges facing society are the high incidence of mental health issues across the population, cardiovascular disease, and neurodegenerative diseases which disproportionately affect the elderly and are of great concern in an ageing society. Dementia and heart disease are the leading causes of death in the UK, and indeed world-wide. Faster and more effective diagnosis and treatment of such debilitating conditions will significantly improve outcomes for these patients. Widespread uptake of the technology will lead to new business growth through commercialisation.
Organisations
Publications

Hexley A
(2022)
Measuring and modelling fixational eye movements
in Journal of Vision

Hexley A
(2023)
Contributed Session II: The relationship between temporal summation at detection threshold and fixational eye movements
in Journal of Vision

Williamson CA
(2023)
Bright-light distractions and visual performance.
in Frontiers in psychology

Young L
(2023)
Poster Session I: Does stimulus image quality affect fixational eye movement characteristics?
in Journal of Vision
Description | The feasibility of imaging candidate structural and functional biomarkers was addressed. Our readiness to obtain measures of neural function, both via system- level proxies and direct functional measures was developed by 1) A research visit to Indiana University to develop expertise in dual-channel blood flow monitoring via adaptive optics scanning laser ophthalmoscopy (AO-SLO), 2) Experimental AO-SLO work on parameterisation of stereotyped behaviour of fixational eye movement characteristics in the normal population and 3) A research visit to Indiana University to develop expertise in AO-OCT for structural and optoretinogram (ORG) measurements. Candidate novel biomarkers were prioritised in collaboration with stakeholders, including oculomotor metrics, imaging of vasculature, imaging of ganglion cells, and functional measures of changes in cell morphology (e.g. ORG). We explored the possibility of utilising ex vivo imaging in mouse as a "screening" for the most promising in vivo human biomarkers. We concluded that direct human imaging was more useful to pursue further as 1) mouse retina is quite distinct from that of humans, so some key biomarkers in humans may not be seen in mouse; and 2) post-mortem tissue is inappropriate for development of functional or longitudinal imaging methods. We met with technology developers, researchers, and healthcare stakeholders to develop our ideas on target biomarkers. We have established a collaborative network across the three universities of Oxford, Newcastle and Manchester, including clinicians (optometrists, neurologists, psychiatrists), biomedical researchers, patients and members of the public, and data scientists, providing a platform for future work. |
Exploitation Route | Through our new network, we have identified several projects for collaborative funding proposals, which will address technological developments required for predictive methods and their future translation to the clinic. We have identified multiple and diverse funding routes, such as charities, technology development streams through the research councils, and the NIHR, dependent on the relative stage of each development. We also engaged with commercial stakeholders who can connect us with additional clinical and commercial partners to expand in the future. |
Sectors | Healthcare |
Description | We have formally identified future routes to impact through engagement with members of the public and patient groups (PPIE), which has started to raise awareness of our research among those that may interact with this technology in the future. Similarly, we have laid the ground work for future developments with support from Medical Physicists, in readiness for future medical device regulatory processes. Our optometry networks have also provided a route into training programmes to educate future generations of healthcare practitioners who would be the primary users of our technology. The work we have done so far has enabled psychiatry, neurodegenerative and vascular disease researchers to envision how our proposed technology could help them develop new diagnostics and therapies. Our clinical stakeholders identified early-stage impact opportunities using our technology to overcome challenges in patient selection for interventional clinical trials. |
First Year Of Impact | 2023 |
Sector | Healthcare |
Impact Types | Societal |
Description | Training material added to graduate course |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Influenced training of practitioners or researchers |
Description | Early detection of cerebrovascular deficits via adaptive optics retinal imaging: Enhancing translation proof-of-concept in PREDICTOR |
Amount | £47,243 (GBP) |
Funding ID | 0011558 |
Organisation | Medical and Life Sciences Translational Fund |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2022 |
End | 07/2022 |
Description | Faculty of Biology, Medicine and Health Capital Equipment Funding - State-of-the Art Technology for High Resolution Retinal Imaging |
Amount | £368,000 (GBP) |
Organisation | University of Manchester |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2023 |
End | 07/2024 |
Description | Lifelong Learning lecture |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Members of Explore Lifelong Learning attended an hour long lecture on "Imaging neurons in the living eye". The talk described the basics of the eye and visual system and how researchers can study these in more detail using high resolution imaging technologies to better understand both the normal healthy retina and how it is altered in diseases that affect the retina, including ophthalmic and systemic diseases. The lecture prompted questions and discussions on a range of related topics and interest from members of the general public in the future of the technology. |
Year(s) Of Engagement Activity | 2023 |
Description | Pint of Science Talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Dr Hampson gave a talk at a local Pint of Science event. The talk title was The Eye as a Window to the Brain and was attended by around 20-30 members of the general public. The goal was to tell the public about how in the future they could get pre-symptomatic diagnosis of neurodegenerative and psychiatric disease during a routine visit to their local optometrists. There were several questions including a discussion on the ethics of diagnosing a disease that there is currently no cure for. |
Year(s) Of Engagement Activity | 2022 |
URL | https://pintofscience.co.uk/event/engineering-from-steel-to-psychiatry |
Description | Recorded presentation for the general public |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Dr Hampson gave a recorded talk for the general public to raise their awareness of how in future they could potentially get a diagnosis of neurodegenerative and psychiatric disease during a routine eye test. The talk has so far had over 150 views. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=qiPAdPpeaHs |
Description | Talk for Optometrists and Ophthalmologists |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | A talk on the uses of adaptive optics OCT for retinal imaging at the Manchester Royal Eye Hospital. The audience were a mixture of Optometrists and Ophthalmologists. This sparked discussion around when changes in the curriculum need to start being made and how pre-symptomatic diagnosis might affect health insurance. |
Year(s) Of Engagement Activity | 2022 |
Description | Talk to Newcastle Child Vision Team contributing to Continuing Professional Development |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | My lab and I presented our research to the Newcastle Child Vision Team as part of their Continuing Professional Development. |
Year(s) Of Engagement Activity | 2023 |
Description | The PREDICTOR project: Prediction and early diagnosis of disease by imaging the eye |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | We held a Patient and Public Involvement event through VOICE, who are a Newcastle-based organisation with an international network of diverse communities of patients, carers and the public who contribute their experiences and views to research and innovation. We held a consultation with a VOICE Research Support Group, consisting of four members of the public with a range of backgrounds and ages, on early diagnostics and the future use of retinal imaging technology within the healthcare system. |
Year(s) Of Engagement Activity | 2022 |