Oculomics – keeping an eye on your healthspan

Occuity’s Dr Emily Patterson explains why ocular biomarkers have a promising future in the quest for longevity.

Using a crystal ball to predict the future – “crystallomancy” – dates back to the first century in Ancient Rome. Although the art of “scrying” (from the word descry: to see something unclear or distant) is practiced to this day by Pagans, modern tools have enabled the modernisation of this ancient pastime. But now, rather than using a crystal ball, scientists can use the eye to predict one’s future or, more specifically, longevity.

Modern-day crystallomancy descries systemic health and disease using ocular biomarkers, and has been termed “oculomics” [1]. The crucial advantage of oculomics over crystallomancy is that it is rooted in science, with the eye sharing many biological features with other systems within the body, including:

  • Aqueous and vitreous humor – derived from the plasma (a component of blood) that allows transportation of lipid-soluble substances through diffusion, and water-soluble substances through ultrafiltration.
  • Lens – continuously-growing, and containing molecules that build up over the lifetime, enabling mapping of molecular history.
  • Retinal vasculature and choroid – the blood-retina barrier matches the blood-brain barrier, and the retina is one of the only places that allows direct visualisation of microvasculature.
  • Optic nerve and ganglion cells – the neurosensory retina is an extension of the brain, allowing direct visualisation of the nervous system.

The eye – not just a window to the soul

Oculomics relies on optical techniques that take biometric measurements or images of the structures within the eye. Such techniques are often used in conjunction with artificial intelligence (AI)-based tools, which enable analysis of large datasets. A significant area of interest for oculomics research is in predicting biological age – a measure of how well your body is functioning – as opposed to chronological age – the number of years you have been alive. Age itself is a significant risk factor for some of the most prevalent chronic diseases – such as cardiovascular, neurological and metabolic disease, as well as cancer – all of which pose major barriers to longevity. By using oculomics to estimate your biological age, it may be possible to issue a “wake-up call” that enables you to make the lifestyle adjustments necessary to increasing your longevity.

Oculomics – keeping an eye on your healthspan

Through the looking glass

From the very front of the eye to the back, age takes its toll on different structures within the eye. For example, cataracts (in the crystalline lens) are a common complaint with increasing age, affecting one in three people over the age of 65 years [2]. Although cataract surgery is a fairly simple outpatient procedure, it can also be indicative of age-related disease, such as sarcopenia (loss of skeletal muscle mass and strength) [3] and Alzheimer’s disease (ongoing decline in brain functioning) [4], which impact both lifespan (living longer) and healthspan (maintaining key physical and mental functions).

The lens comprises 60% protein [5] – the highest concentration of any bodily tissue. However, in aging and disease, harmful proteins can accumulate. One such example is Advanced Glycation End-Products (AGEs), which are associated with higher blood-glucose levels, and therefore risk of diabetes. AGEs are naturally fluorescent and, when illuminated by specific wavelengths of blue light, they glow green, providing a potential opportunity for non-invasive assessment of diabetes risk using oculomics. Moreover, as the lens is a continuously growing tissue, it essentially allows the discerning crystallomancer to travel back in time and discriminate between old and new molecules.

“Understanding what molecules are present in the human body, and where they are building up, is critical to many diseases,” says Dr Alistair Bounds, Senior Research Scientist at Occuity. “Oculomics promises new insight into these critical disease biomarkers with unprecedented ease of measurement for clinicians.”

Sense of humor

While the crystalline lens provides a history of the eye, the aqueous and vitreous humors provide a snapshot of the present. The aqueous humor is a clear, watery fluid that fills the space in front of the lens in the eye and the vitreous humor is a clear gel-like substance that fills the space between the lens and retina in the eye. Both humors are derived from the plasma (the liquid portion of the blood) and allows transportation of lipid-soluble substances through diffusion, such as fats, as well as water-soluble substances through ultrafiltration, such as glucose. One potential application for oculomics is to assess the properties of the aqueous humor to provide a snapshot of present blood-glucose levels. Not only could this be used to non-invasively monitor those who already have diabetes, but also by those who do not have diabetes to optimize their diet and lifestyle.

“At the moment, people with diabetes have to monitor their glucose levels via needle-based systems, where they have to puncture the skin to make a measurement,” says Dr Dan Daly, Founder and CEO at Occuity. “This seems medieval to us, as the same data is available in the eye and this can be accessed non-invasively with optical systems.”

(Not so) hidden depths

As we turn our attention from the front of the eye to the back, we also look to the future. Many studies have combined oculomics with AI tools to predict biological age from retinal biomarkers, such as retinal vasculature [1,6], and even linked this to chronic disease risk, such as cardiovascular disease and cancer [7]. High resolution imaging tools also enable direct visualisation of the neural layers within the retina, which can show signs of neurodegenerative diseases, such as Alzheimer’s disease [1,6], Parkinson’s disease [8], multiple sclerosis [6,9], and even rare conditions, such as Lafora disease [10]. In many cases, the oculomic signs are present before symptoms arise. For example, it has been shown that proteins related to Alzheimer’s disease (such as amyloid-beta) accumulate at least one decade prior to cognitive decline [11] and these proteins also accumulate in the retina [12]. This is particularly pertinent to clinical research and drug development, as it enables identification of those who may benefit from intervention before irreversible damage has taken place.

Oculomics – keeping an eye on your healthspan
Dr Emily Patterson is a Retinal Imaging Scientist at Occuity

Advances in imaging technology mean that we can now detect biomarkers at cellular resolution. We are continually finding new applications for imaging techniques to detect disease before it takes hold, providing the opportunity to intervene and potentially avoid disease altogether. It’s definitely an exciting time for oculomics research!

Predicting the future

Crystallomancy has come a long way since Ancient Roman times, and it makes one wonder whether the scryers of the past could have predicted the transformation of orb-gazing from a mystical art to a rigorous science. Not only does Oculomics enable us to look into your past and present, but also has the potential to look into your future, providing you the opportunity to change your “fate”. Although we cannot be sure what form the advancements in imaging and AI tools will take over the coming years, we can be sure of one thing – that oculomics has a promising future in the quest for longevity.

About Emily Patterson

Emily initially trained as an experimental psychologist at the University of Warwick and later went on to obtain a PhD in Optometry and Visual Science at City University. Continuing her time in academia, she then worked as a postdoctoral researcher in a retinal imaging lab at the Medical College of Wisconsin, studying adaptive optics. After five years in the US, Emily returned to the UK to work at the UCL Institute of Ophthalmology, where she became a Principal Investigator for a project investigating oculomics for diabetes.

Emily joined Occuity in February 2023 as a Retinal Imaging Scientist where she performs key roles in grant management, clinical research, dissemination, and ethics.

Photographs/diagram courtesy of Occuity

[1] https://pubmed.ncbi.nlm.nih.gov/32704412/
[2] https://www.bmj.com/content/316/7145/1643
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437169/
[4] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)12981-9/ppt
[5] https://pubmed.ncbi.nlm.nih.gov/3052280/
[6] https://pubmed.ncbi.nlm.nih.gov/36614953/
[7] https://academic.oup.com/ageing/article/51/4/afac065/6561972
[8] https://pubmed.ncbi.nlm.nih.gov/30721408/
[9] https://pubmed.ncbi.nlm.nih.gov/37971733/
[10] https://www.sciencedirect.com/science/article/pii/S2451993621001559
[11] https://pubmed.ncbi.nlm.nih.gov/14593169/
[12] https://insight.jci.org/articles/view/93621