Professor Mark Daniell

00:41

S1

On Vision Australia Radio, this is Vision Extra with Peter Greco.

S2

Let's welcome to the program Professor Mark Daniel from the Centre for AI Research specialises in the area of corneal conditions. And Mark, welcome to the program and thanks so much for your time. 

S3

Oh, it's a pleasure. Good to be here.

S2

One of the things that you were working the ear of is the condition of Fuchs endothelial dystrophy. Can you tell us a bit about what the condition is? And then your quite remarkable work that's going on into that particular condition. Yeah.

S3

Thanks, Peter. So Fuchs endothelial dystrophy is probably the commonest cause for acquiring a corneal transplant in Australia. What it is, is it's a disease of the the cells that line the inner lining of the cornea. Now, the function of those cells is to maintain the clarity of the cornea. The cornea is normally crystal clear in life, and that clarity is maintained by a layer of cells called the endothelial cells that pump fluid out of the cornea and keep it in a in a crystal clear state. 

What happens in Fuchs in the field dystrophy is there's a disease process that inherited disease of those cells. And eventually with time, they fail to function. And that usually means that initially the eyes you can see the abnormal cells and the patients might notice some glare symptoms or trouble with seeing fine detail. And as the disease progresses, the cornea becomes more swollen, particularly in the mornings. Early on, they get a mess of their vision and eventually the whole cornea compensates and become swollen all of the day, in which case the vision drops quite dramatically. What we do is, is we remove those endothelial cells and replace them with a with a transplant with the donor cells.

S2

And is inheritance kind of the biggest risk factor?

S3

Yeah, that and old age. So as you get older the proteins that the abnormal cells deposit build up and you get what we call [indistinct] to little lumps on the back of the endothelium, which you can see. And they seem to damage the function of the endothelial cells. So it does tend to run in families. We haven't worked out the exact inheritance yet. We're doing some some work on that area, but it does seem to be a relatively common condition, at least in Australia and the Western world. And as you get older, the manifestation become more apparent.

S2

Is it quite easy to diagnose that? 

S3

Yeah, from a specialist point of view or maybe going back a step. The people quite obviously notice that change in their vision that might alert them to getting some professional help. I think early on it's quite can be quite tricky to see. You've got to look very closely at a very tiny layer of cells on the back of the cornea and this can be a problem in patients who are having cataract surgery if it isn't noticed beforehand. The cataract surgery can can damage those cells and that can lead to a failure of the cornea to clear after cataract surgery.

So a number of patients I see have got a mixture of some abnormal endothelial cells and cataract. And once the cataracts removed, their cornea compensates. I think as the disease progresses, though, it becomes more and more obvious, both to the patient and to the doctor. And when the cornea is sort of decompensated and swollen, then it's usually fairly clear what the diagnosis is.

S2

And what about as far as the sort of corrective surgery, if you like? Is that kind of available for everyone? It kind of can everyone or anyone that's diagnosed be a candidate or is it not quite as straightforward as that?

S3

No, a little bit more complicated than that, unfortunately. So there's no medical treatment at the moment. You know, we're looking into various possibilities there. Once the cornea becomes decompensated, the only treatment is a corneal transplant. And we used to do full thickness corneal transplants, take out the whole cornea and sew in another cornea, which is quite a big operation for the eye. It would take, you know, 12 to 18 months for the eye to recover, for the stitches to come out and the vision to be restored. 

The newer way of doing that, it's just to replace that layer of cells. So we call it an endothelial deposit. So it's sort of a strip the the disease cells off the back of the cornea and then using a donor cornea, we just take off that layer of cells and apply that into the into the back of the eye, hold it in position with an air bubble and usually the recovery there is much quicker. They can often see within a few weeks.

05:11

S2

And is that because, you know, in layman's terms, the operation, if you like, is is smaller in terms of the, you know, the size of the transplant or is that too simple a way to put it?

S3

Yeah, no stitches is the simple way to put it. So, you know, the way we used to do it, you'd have 16 stitches that would require a great deal of skill and and accuracy in placing them and getting the attention exactly right to get it all even. And then the whole wound would have to heal this way. We use a very tiny wound, just a three millimetre wound, which may require one stitch which can go out, come out of a couple of weeks. That means the natural curvature of the cornea is maintained. And so once the cells start adhere and start to work, then your vision returns pretty much to its best potential.

S2

So 16 stitches in the eye. It's not that big, is it? Sort of 16 stitches.

S3

Because it's an eight millimetre diameter corneal transplant we usually use, and 16 stitches have to be placed absolutely perfectly to get the best possible result. And if you put less than that, it tends to not be watertight, which is obviously bad. Sometimes you need more, but then that distorts the curvature of the cornea a little bit. So it's quite tricky, quite a degree of hand-eye coordination to get it to strike.

S2

Yeah, pardon the pun. That's amazing, isn't it? Do people get it in both eyes if they are diagnosed with a condition?

S3

Yeah, it's a bilateral condition. Often it can be a little asymmetric. You know, if you've had cataract surgery, it might present in one eye before the other, but often it's in both eyes.

S2

So the new work or the new way of doing it, you still rely on on donors to sort of make the the bit that you're transplanting, without putting it too crudely, make that available.

S3

Yeah, exactly. So which is sort of the problem that our labs have been working on at the moment, it's a 1 to 1 transfer. You have one donor who's who's deceased and donated their their organs. And we apply that to to one patient, which is fine when we've got a well-organised banking system that can safely procure and store and then distribute the corneal tissue. But many other countries in the world don't have that sort of system. And so there's a huge shortfall in the number of of the amount of donor tissue available. 

And so we've been working on that from a number of angles, but basically trying to tissue engineer a cornea. So make a cornea in our laboratory, taking a few cells and amplifying them in the lab. They normally don't grow in the body, but we've worked out ways of getting those cells to to divide and multiply into. That way we can use maybe produce 30 or 50 transplants from each donor. And with the engineers at the University of Melbourne have scaffolds that we can grow these cells on which mimic then the normal sort of surgery that we used to doing so we can grow the cells to a confluent sheet on our scaffold, do our normal sort of surgery. And then the hydrogel that the engineers have made is is quite amazing. It slowly dissolves without causing any toxicity inside the eye, leaving the cells firmly attached on the back of the cornea. 

S2

Wow. So you still need the data to get the the original cells and then sort of multiply those cells from the original donor?

S3

Exactly. So, you know, the other more blue-sky area of research is to is to get the patient's own cells, maybe, you know, a skin cell or something and then turn that into a corneal cell. And then they've obviously got unlimited supply. There's a few that's using what we call induced pluripotent stem cells. So we turn the skin cell into a type of stem cell. We get that to grow that grows in an unlimited way. And then we've worked out ways of getting those stem cells to turn back into corneal cells. And that's still at a fairly basic level of research.

And there's a whole lot of issues that we'd have to deal with to get that to work as a possibility. But that's probably going to be the future. The intermediate step, though, is, as you say, we take one donor and turn it into 50 or 30-to-50 donors and then we've overcome the sort of shortfall of corneas that we need at the moment.

S2

And is rejection an issue when you're taking one donor and sort of spreading it to 30 or 50 recipients?

S3

Yeah, so that's an interesting question. With doing a full thickness corneal transplant, rejection is a major issue. Maybe 30% of grafts suffer rejection at five years when we just do a single layer of cells, that that level of rejection is markedly reduced. So maybe down to 1 or 2% at most. 

S2

Wow. That's interesting. 

S3

So we've been sort of thinking about that as well. What's causing the rejection? And it may not maybe that the endothelial cells aren't causing the rejection, but the stromal... some cells in the stroma we call them cells or antigen presenting cells, and they might be going off to the lymph node inducing the rejection, and then the body rejects the endothelial cells and attacks them. So by just transplanting a strip of endothelial cells, they're sort of stuck on the cornea and don't go to the regional lymph nodes and they probably don't have the same rejection inducing potential. And so we think rejection is going to be much less of an issue than doing it the traditional way. 

10:43

S2

Gee, that's extraordinary, isn't it? What about you said that, you know, 30% have rejection within five years. So I guess I was always under the impression that, you know, if you're going to get a rejection, it's going to be kind of early on. So it can take a while for the body to reject a transplant.

S3

That's right. Yeah. No, that's a common misconception. You know, it is possible to get a really acute rejection early on, but often it's... you've got a lot of immunosuppressive drugs at that time. And we see rejections, you know, often quite late, you know, months and even years after the original surgery. So you're never fully, you know, in the clear as far as that goes.

S2

Is the rejection kind of an easy thing to diagnose, if you like, this sort of something happen either blood test wise or to the eye itself, that there's a rejection about to happen or a rejection in the happening right now?

S3

Yeah, again. So, you know, all of that is fairly subtle. You know, there's small signs and little things that you've got to notice. The patients would notice the vision going off, you know, the vision becoming blurry there. It might become red or photophobia, you know, sensitive to light. When the doctor looks in, they've got to notice tiny little cells floating inside the eye. And, you know, some people might miss those. And it can be particularly difficult to pick up rejection in our endothelial transplants where there's much less inflammation. 

And the layer of cells, the donor cells is so, so thin. It's very hard to see often. So it can be tricky to pick it up quickly and early enough. If we pick it up quickly, you can treat it. You can... we can pour on anti-rejection medications, you know, like steroid drops and so on. And that can reverse the signs and we can save the graft. If it's sort of not noticed until late, then the graft can be lost and we have to go back to square one and do another transplant.

S2

Okay. And that's, of course, assuming that a transplant is available. 

S3

Yeah, well, that's right. It's a bit of planning and and booking and all that sort of stuff as well.

S2

And we're running out of time. We could chat for hours. This is amazing. I just can't fathom how incredible the human body is and the human eyes. I guess you probably see it every day and you probably kind of maybe, pardon the pun, become immune to it, perhaps.

S3

Oh, no. This well, not only is the human eye and the human brain amazing, but all the science behind it. It's pretty extraordinary as well. And I'm lucky to work with a team of scientists that understand the details of of what's going on in the way the cells are growing and why they're dividing and why they're not dividing, how they're attaching onto these various scaffolds we're using, how we can get them to stick better inside the eye and really, you know, push on the surgery and the science to to a new level so that we can hopefully do things better than we did them when I started 20 or 30 years ago.

S2

Well, so I'm just always amazed at the incredible talent and the work that people at the Centre for Research and indeed other people in this sector are doing. Mark, great to talk to you. Congratulations on the work that you're doing. May you keep it up for a long time to come. And again, it's it's been an absolute fascination. Speaking to you, I wouldn't mind one day maybe gatecrashing into one of your laboratories and having it all explained sort of firsthand because it just sounds remarkable. But thanks again for spending some time with us. 

S3

Oh, Peter, it's a big and absolute pleasure. And keep your eyes posted because there might be some news coming from the government in the next few months about all of this.

S2

Okay. We had some news on the program last week regarding some spinal cord injury research. So when the news comes through, we'd love to get you back to talk about it.

S3

So I could only say that that's the chat to you.

14:26

S2

There you go. How good is that? That's Professor Mark Daniel, who's a specialist in the area of ophthalmology and also in particular, recording diseases from the Centre for Research with some really amazing and so insightful information. That is it for the program. If you've missed some of them, if you'd like to hear it again, you can search for an extra on the iTunes store on Spotify or your favorite podcast service.