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Gap between ‘retinal age’ and real age may signal likelihood of death

retinal age

The difference between the biological age of a person’s retina and their actual age is linked to their risk of death, according to new research involving Melbourne academics published in the British Journal of Ophthalmology.

Professor Mingguang He, from the Centre for Eye Research Australia, along with researchers from Monash University’s e-Research Centre and Medical AI Group, co-authored the paper contributing to a body of evidence suggesting the retinal microvasculature might be a reliable indicator of the overall health of the body’s circulatory system and brain.

The researchers state that while the risks of illness and death increase with age, these risks vary considerably among people of the same age, implying that “biological ageing” is unique to the individual and may be a better indicator of current and future health.

While several tissue, cell, chemical, and imaging-based indicators can detect biological ageing that is out of step with chronological ageing, the paper suggested these techniques are fraught with ethical/privacy issues as well as often being invasive, expensive and time consuming.

Prof He and his research team turned to deep learning to determine if it could accurately predict a person’s retinal age from fundus images to see whether any difference between this and a person’s real age, referred to as the “retinal age gap”, might be linked to a heightened risk of death.

Professor Mingguang He, from the Centre for Eye Research Australia, was involved in the study.

The researchers drew on 80,169 fundus images from 46,969 adults aged 40 to 69, all of whom were part of the UK Biobank, a large, population-based study of more than half a million middle aged and older UK residents.

Some 19,200 right eye fundus images of 11,052 participants in relatively good health at the initial Biobank health check were used to validate the accuracy of the deep learning model for retinal age prediction.

This showed a strong association between predicted retinal age and real age, with an overall accuracy to within 3.5 years.

The retinal age gap was then assessed in the remaining 35,917 participants during an average monitoring period of 11 years.

During this time, 1,871(5%) participants died: 321 (17%) of cardiovascular disease; 1,018 (54.5%) of cancer; and 532 (28.5%) of other causes including dementia.

The proportions of ‘fast agers’– those whose retinas looked older than their real age – with retinal age gaps of more than three, five, and 10 years were, respectively, 51%, 28%, and 4.5%.

Large retinal age gaps in years were significantly associated with 49%-67% higher risks of death, other than from cardiovascular disease or cancer.

And every one-year increase in the retinal age gap was associated with a 2% increase in the risk of death from any cause and a 3% increase in the risk of death from a specific cause, other than cardiovascular disease and cancer, after accounting for potentially influential factors, such as high blood pressure, weight (BMI), lifestyle, and ethnicity.

The same process applied to the left eyes produced similar results.

The researchers noted their work was an observational study so it can’t establish cause. They also acknowledged the retinal images were captured at one moment in time, and that the participants may not be representative of the UK population as a whole.

“Our novel findings have determined that the retinal age gap is an independent predictor of increased mortality risk, especially of non-[cardiovascular disease]/ non-cancer mortality. These findings suggest that retinal age may be a clinically significant biomarker of ageing,” the paper stated.

“The retina offers a unique, accessible ‘window’ to evaluate underlying pathological processes of systemic vascular and neurological diseases that are associated with increased risks of mortality.

“This hypothesis is supported by previous studies, which have suggested that retinal imaging contains information about cardiovascular risk factors, chronic kidney diseases, and systemic biomarkers.”

The new findings, combined with previous research, add weight to “the hypothesis that the retina plays an important role in the ageing process and is sensitive to the cumulative damages of ageing which increase the mortality risk,” they explain.

The study also involved researchers from Guangdong Academy of Medical Sciences, Sun Yat-Sen University, Guangzhou Vision Tech Medical Technology, and the University of Bonn in Germany.

It was funded by State Key Laboratory of Ophthalmology; National Natural Science Foundation of China; Science and Technology Program of Guangzhou, China.

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