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Retinal Imaging Can Predict Cardiovascular Mortality

Cardiovascular disease (CVD) and mortality risk could be detected by routine retinal scanning, according to a new study using data from the UK Biobank Eye and Vision Consortium and the European Prospective Investigation into Cancer (EPIC)-Norfolk study.

The researchers, from St George's University of London, Cambridge University, Kingston University, Moorfields Eye Hospital and University College London, developed a method of artificial intelligence (AI)-enabled imaging of the retina's vascular network that could accurately predict CVD and death, without the need for blood tests or blood pressure measurement.

The system "paves the way for a highly effective, non-invasive screening test for people at medium to high risk of circulatory disease that doesn't have to be done in a clinic", they said. "In the general population it could be used as a non-contact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention." Optometry specialists welcomed the prospect and hailed it as "an exciting development".

Retinal Vessels Give an Accurate Early Indicator of CVD

The study, published online in the British Journal of Ophthalmology,was based on previous research showing that the width of retinal arterioles and venules seen on retinal imaging may provide an accurate early indicator of CVD, whereas current risk prediction frameworks aren't always reliable in identifying people who will go on to develop or die of circulatory diseases. 

The researchers developed a fully automated AI-enabled algorithm, called QUantitative Analysis of Retinal vessels Topology and siZe, or QUARTZ, to assess the potential of retinal vasculature imaging plus known risk factors to predict vascular health and death. They applied QUARTZ to retinal images from 88,052 UK Biobank participants aged 40 to 69, looking specifically at the width, vessel area, and degree of tortuosity of the retinal microvasculature, to develop prediction models for stroke, heart attack, and death from circulatory disease.

They then applied these models to the retinal images of 7411 participants, aged 48 to 92, in the European Prospective Investigation into Cancer (EPIC)-Norfolk study. They then compared the performance of QUARTZ with the widely used Framingham Risk Scores framework.

The participants in the two studies were tracked for an average of 7.7 and 9.1 years, respectively, during which time there were 327 circulatory disease deaths among 64,144 UK Biobank participants (average age 56.8) and 201 circulatory deaths among 5862 EPIC-Norfolk participants (average age 67.6).

Vessel Characteristics Important Predictors of CVD Mortality

Results from the QUARTZ models showed that in all participants, arteriolar and venular width, venular tortuosity, and width variation were important predictors of circulatory disease death. In addition, in women, but not in men, arteriolar and venular area were separate factors that contributed to risk prediction. 

Overall, the predictive models, based on age, smoking, and medical history (antihypertensive or cholesterol lowering medication, diabetes, and history of stroke or myocardial infarction) as well as retinal vasculature, captured between half and two thirds of circulatory disease deaths in those most at risk, the authors said. 

Compared with Framingham Risk Scores (FRS), the retinal vasculature (RV) models captured about 5% more cases of stroke in UK Biobank men, 8% more cases in UK Biobank women, and 3% more cases among EPIC-Norfolk men most at risk, but nearly 2% fewer cases among EPIC-Norfolk women.  However, the team said that while adding RV to FRS resulted in only marginal changes in prediction of stroke or MI, a simpler non-invasive risk score based on age, sex, smoking status, medical history, and RV "yielded comparable performance to FRS, without the need for blood sampling or BP measurement".

Vasculometry Low Cost, Non-Invasive and With High Street Availability

They concluded: "Retinal imaging is established within clinic and hospital eye care and in optometric practices in the US and UK. AI-enabled vasculometry risk prediction is fully automated, low cost, non-invasive and has the potential for reaching a higher proportion of the population in the community because of 'high street' availability and because blood sampling or sphygmomanometry are not needed.

"[Retinal vasculature] is a microvascular marker, hence offers better prediction for circulatory mortality and stroke compared with MI, which is more macrovascular, except perhaps in women. 

"In the general population it could be used as a non-contact form of systemic vascular health check, to triage those at medium-high risk of circulatory mortality for further clinical risk assessment and appropriate intervention."

In the UK, for example, it could be included in the primary care NHS Health Check for those aged 41 to 74, they suggest.  In addition, 'high street' retinal scanning could directly feed into primary medical services and help achieve greater screening coverage for older age groups, who are likely to attend an optometric practice for visual correction, especially with the onset of presbyopia. "This would offer a novel approach to identify those at high riskof circulatory mortality, which is not currently screened for," the team said.

Test Could Help to Identify High Risk Individuals

In a linked editorial, Drs Ify Mordi and Emanuele Trucco of the University of Dundee, said that CVD remains a significant cause of mortality and morbidity and the most common cause of death worldwide, accounting for a quarter of all UK deaths – and its burden is increasing. "Identification of individuals at high risk is particularly important," they said, but current clinical risk scores to identify those at risk "are unfortunately not perfect", so miss some of those who might benefit from preventative therapy.

"The retina is the only location that allows non-invasive direct visualisation of the vasculature, potentially providing a rich source of information." In the new study, the measurements derived with the software tool, QUARTZ, were significantly associated with CVD, they said, with similar predictive performance to the Framingham clinical risk score.

"The results strengthen the evidence from several similar studies that the retina can be a useful and potentially disruptive source of information for CVD risk in personalised medicine." However, a number of questions remain about how this knowledge could be integrated into clinical care, including who would conduct such a retinal screening programme and who would act on the findings?

The editorial concluded: "What is now needed is for ophthalmologists, cardiologists, primary care physicians, and computer scientists to work together to design studies to determine whether using this information improves clinical outcome, and, if so, to work with regulatory bodies, scientific societies and healthcare systems to optimise clinical workflows and enable practical implementation in routine practice."

'Exciting Development That Could Improve Outcomes'

Asked to comment by Medscape UK, Farah Topia, clinical and regulatory adviser at the Association of Optometrists, said: "This is an exciting development that could improve outcomes for many patients by enabling earlier detection of serious health risks. Patients attend optometric practice for a variety of reasons and this interaction could be used to a greater extent to help detect disease earlier. With optometrists available on every High Street, in the heart of communities, it's an element of primary care that can be accessed quickly and easily, and optometrists are also already trained to have health and lifestyle discussion with patients."   

She added: "Retinal photographs are regularly taken when patients visit an optometrist, so being able to further enhance this process using AI is exciting.  

"We look forward to seeing how this area develops and how optometrists can work together with other healthcare sectors to improve patient outcomes and ease the burden the NHS currently faces." 

The study was funded by the Medical Research Council Population and Systems Medicine Board and the British Heart Foundation.

Lead Image Credit: Moment/Getty Images