Liquid biopsy from the eye gives new health insights

With a view to helping diagnose diseases earlier...
20 October 2023

Interview with 

Kez Latham, Anglia Ruskin University & Vinit Mahajan




We’ve long used eye tests as a way of checking the health of our vision, but increasingly the medical community is finding ways of using our eyes as a way of examining the health of the rest of our body. Will Tingle has been taking a look…

Will - As a keen bird spotter and cameraman, I pride myself on having tip top vision. And so any research into maintaining healthy vision is very important. In a minute, we'll hear how researchers at Stanford University have used fluid in the eye to age the eye and even spot the early onset of certain diseases. But before that, back in the here and now, what can you or I learn about our own body's health from our eyes? Well, that's why I went to Anglia Ruskin University to have a checkup.

Kez - Hello, I'm Kez Latham. I am Professor of Optometry here at Anglia Ruskin University.

Will - How would you be able to tell about any kind of general health condition by looking at my eye?

Kez - The eye is composed of lots of different components, each of which can be affected by systemic diseases that affect the rest of the body. And the particular thing that we are definitely looking for is the blood vessels. When we look at the back of the eye, we can see the blood vessels spread across the retina, and it's the only place in the body that you can see blood vessels and visualise them directly without having to open the skin.

Will - Where do I get started?

Kez - What we're going to do to start with is I'm going to do some tests of your visual function, just to see how your eyes are doing at the moment in terms of how they're performing. So what we'll do is I'll get you to look over at that letter chart in the mirror there, and I will get you to start on a line that's comfortable and then carry on reading down the letters as far as you can go.

Will - H, E, P, R, V.

Kez - Lovely. How about the ones below that?

Will - D, N, O, H, N, E.

Kez - So you have got exceptionally good vision there. In an ideal world, what I would like is another line underneath that you can't see, just so that I can tell I've got to threshold, but you are reading the smallest line of letters that I've got there, which is excellent.

Will - You can see listeners why I can't afford to lose this.

Will - Now, I've been put into a booster seat.

Kez - Okay. Now I'm just going to adjust the height of the chair a little bit here. This looks like quite an intimidating machine, but basically all it is is a bright light and a microscope that will allow me to look at your eye under magnification. So what I'm going to do first is I'm going to have a look at the front of the eyes and just check the structures at the front of the eye to see if there is anything we need to comment on, there. Next, I'm going to do the same again looking at the eyes now, but this time I'm going to hold up a lens as well and that lets me look through to the back of the eyes, here. That's really super. So looking at the health of the eyes both front and back, I'm not seeing any problems there either in terms of issues that relate to the eye or issues that relate to other things that are going on in the body. So I can give you a clean bill of health, but hopefully that hasn't put you off from having an eye exam. We generally recommend for most people that you would have an eye exam every two years as part of your routine health checks. For some people it does need to be more frequent. Often children, if their vision is changing quicker, or older people where there's more likelihood of things changing with time.

Will - Always good to have a clean bill of health, but say there was something wrong: what are your options? Well, to get a better look at your eye, there's two ways of doing things. The first is you can take a tissue sample from the eye. The issue with that, of course, is that your eye is non regenerative, so won't grow back. The other way of doing things is to take a sample of the eye's liquid. It's called a liquid biopsy. And that plays very heavily into what Vinit Mahajan and his team at Stanford University have been doing. Thanks to some remarkable advancements in protein mapping, they have been making some very interesting findings about our eyes.

Vinit - When patients come in for regular eye surgery, let's say cataract surgery, fluid is removed from the eye and frequently just thrown away. But we collected that fluid and used newer proteomics techniques. So proteomics means, instead of just measuring one protein, we can actually measure several hundred or even thousand different proteins.

Will - Is that the idea then, that you are less likely to damage the eye, but is the trade off there that you don't really get as clear a picture, if you'll pardon the pun, as if you use samples directly?

Vinit - So that's a great question. When we take a liquid biopsy, it means we're taking some fluid, almost like taking the blood, and our hypothesis was that the fluid inside the eye is going to be really enriched with lots of proteins coming from the retina and different kinds of tissues within the eye. All these proteins would collect in there like a bunch of proteins or little molecules in the ocean. But the real challenge is where did those proteins come from of the million different cells and different cell types? We don't know where those proteins came from, they're just a big collection. And so a postdoctoral fellow in the lab, Julian Wolf, worked out a computer method that combined proteins and gene expression maps, and he connected the proteins to this DNA map. And what that allowed us to do was actually figure out which cells the proteins had come from.

Will - That in and of itself is remarkable, but I guess the question is what's the use of that? What's the use of knowing what came from where?

Vinit - With so many proteins, and mapping them back to the cells, we could actually see which cells were involved in different kinds of diseases and in specific diseases. The types of proteins they leaked were different between diseases.

Will - Ah, so you can tell which diseases are prevalent by looking in the eye. This is almost like an early diagnosis system?

Vinit - Very much so. And we had some different kinds of surprises. In the case of diabetes, for example, we could see that in advanced diabetes there was a different kind of immune cell that really hadn't been implicated in the disease. That cell was starting to show up in the eye and cause damage. One of the really interesting things that we were able to do, because there's so much data here, is we were able to use artificial intelligence to create a biological clock for the eye. So we know that different parts of our body seem to age at different rates. So a lot of our patients are super healthy except for their eyes: it's as if their eyes had aged more than their muscles or their heart or their brain. And we found using the artificial intelligence algorithm that if we measured 26 proteins, we could predict the chronic logical age, the actual birthdate of our patient, just by measuring those proteins in the eye. But what was really interesting was, we all have this question that, if we have a disease, does that actually accelerate ageing? And what we found is that in diabetes and inflammatory eye disease, this biological clock was accelerated. So it was as if a patient's eye was as much as 30 years older than their chronological age.


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