Oh thank you, thank you so much for the introduction and welcome everyone. I've been hearing Ron's presentation, so for those that you have, you'll see that I'll be giving a bit more detail to some aspects of what, he's gone through. And also I just wanted to give a, a bit of a notice that this is really a bit of an unusual of the presentation because What I'm gonna try and explain is how ulcers truly heal and how do we expect ulcers and certain types of ulcers to heal?
How can you as a clinician assess that this ulcer actually is getting better? And this is not something you can learn in an hour of a lecture, but I'm hopefully gonna be able to give you some hints that will help you to develop this knowledge and feel a bit more confident that that ulcer is actually healing and that you're doing the right job, OK? So let's start the plan for today.
So we're gonna go through some corneal key facts, so some basic standard knowledge that we need to have before we move to understanding the physiopathology of, of corneal healing. Then we'll talk a bit about the epithelial ulcers and some of the kids ulcers, which, we, we go there in a bit more detail. And then some stromal ulcers, a bit more complex ulcers to interpret.
Corneal perforation, how can I identify them, and then we go through a bit of a review of what we've seen and some tips to help you in your day to day practise. So some corneal key facts, yeah, we've got the cornea. This is the section of a, of a globe and we're gonna go to the corneal part which is the front, the window of the eye as we say.
And we've got the epithelium which is the more outer layer of the cornea, then we have the stroma, and then we have the deceme membrane and then the endothelium. All right. So, in this schematic, what I've done is, to put the stroma green because that's what stains with fluorescent, and it's a very useful tool that we use in our clinical examination.
So try to remember that. And this is an histopath picture that I've put just so you see the the width of its structure, OK? So we can see how the actual epithelium is more or less 77% of the full corneal thickness.
And then we have the stroma which is 90% of the, of the corneal stroma. Over there we have the, the, the seme membrane which is more or less it depends with, with age, but it, it can be about 10 to 20 micrometres and then the endothelial cell layer which is like a red blood cell in with the 7 microbes, OK, so really, really thin. So the corneal thickness as Ron has said, is around 500 micrometres and more than 90%, as we've said, is the stroma, is that collagen is a fibrous tissue.
There's some cells there that get out the side. Which if they are activated when there's been a disease, or, or a trauma, they can transform into myofibrocytes and they can, or they are the responsible for tissue remodelling. And we'll talk about them a bit later on.
Another important key fact is that innervation of the cornea, the cornea is really highly innervated, but most of the innervation of the cornea is on the upper half of the cornea or the, on the upper fourth in the most superficial structure or superficial part of the cornea. And as we go deeper into the cornea, that in Nation reduces the amount of of nerve endings that the cornea has. And this, this can cause some issues when an owner is seen a dog with a or a cat with a corneal ulcer, a superficial one, the cat dog is very painful and a few days later, the owner tells you so much better eye's less painful, eye open.
That might be great because it might mean that the patient has healed, but it could well be that actually what has happened is that it has progressed and gone deeper, OK? So that's something to take into account when we are assessing our patients. So let's go through some examples of what happens if.
So what happens if I remove the whole epithelium of the cornea? So I strip it off, yeah. Imagine that.
So, as Ron mentioned, what's gonna happen is that the tear film, the water that is within the tear film will go into the stroma and will hydrate the stroma. That's gonna cause a corneal edoema and it's gonna increase my corneal thickness in up to 200% more. What we do know is, that, that epithelium is gonna be able to grow over in 7 to 10 days.
That is, if it's a completely healthy young patient, yeah. So we're gonna have stromal hydration because we're gonna have that tel embedding into my stroma. And actually, when do we see this in clinical practise?
When do we see that there's an epithelial damage? Well, we see that when there's a corneal ulcer actually, we've said that the fluorescent will stay in the stroma. Therefore, it will be a tool that I can use to evaluate if the epithelium is missing, OK?
Very basic, but I, I thought I would go to that to just basic, so we are all in the same, in the same spin. So what happens, another, another situation. Let's say I'm gonna be removing the whole of the endothelium.
So the endothelium, as Ronalre has mentioned, is is pumping out all that aques out of the, of the cora. So it's permanently in a Kind of dehydrated state, so it's transparent and that's the job of the endothelium. What happens is that if you stop that from happening and you remove the whole endothelium, is that the increasing thickness is gonna be much more.
So the corneal edoema of endothelial origin is gonna be much more severe than that of the epithelial. Again, we're gonna have a stromal hydration because we're gonna have aqueous pumping into the stroma and and causing that gloss appearance that I was showing you. And when do we see endothelial damages?
Most of the times when we have UVI, imagine when we have UVIS, we have an inflammatory environment in the aqueas with inflammatory cells, with prostate glandins, and all of that the environment is quite toxic for the endothelium and that leads to an endothelium cells not being able to work and therefore, they fail and auss can go into the stroma. Another situation is the high intraocular pressure. So patients, for example, with glaucoma, with because of the intraocular pressure, the pressure that the endothelium, that mechanical pressure that the endothelium is having, will lead to aqueous going into the stroma and hence we're gonna have again called lyema.
So those are 22 situations where you can see cornea lyema, that loss appearance of the cornea, but also, we know that some pathologist will, will make blood vessels grow into the cornea and that's what we call neovascularization. So Vessels in the cornea. The cornea is transparent and should always be transparent.
And if it's not, it's probably because there is some pathology there and one of those pathologies is bringing blood vessels into the cornea. And actually can be quite helpful for us to know for how long has this eye had problems for. Because for the eye to start all the machinery to build all those blood vessels, it takes up to 24 hours.
And then once the, the, the eye is ready to build up those blood vessels, the eye is able to build a millimetre length every day. OK, so it can gives us an idea if we see a very long blood vessel, that that didn't happen yesterday, that there's been a pathology in the cornea for much more time, yeah. And because we have those blood vessels that are fairly new or relatively new, they can leak contents and that can lead to a bit of edoema around that, that, that blood vessel and that will also help us to see some of the pathologies.
So a bit of a review, we've seen that the aqueous can lead into the cornea when there's endothelial damage. Tearin can cause corneal lyema when there's epithal damage and we can see that with our fluorescence thing. And then, even if the endothelium or the epithelium are healthy, if there's blood vessels, we can also see corneal edoema, and it's more, mostly around, excuse me, mostly around the, the blood vessels that have been built in the cornea.
So, what opacities can we see? Yeah, because that's what is gonna help us to define what kind, what sort of corneal pathology we have. So if you go area by area, we've seen corneal edoema, we've discussed all of those three when there's epithelial damage, endothelial and neovascularization.
Pigmentation, you've seen quite a few pictures of corneal pigmentation with those that were withdrawn in the presentation before and he's discussed how pigment is not a disease, is basically a clinical sign and it indicates that there's chronicity of superficial disease so that there is a long-term corneal disease there. The pigment, however, can also come from the iris and that I'll show you a picture a bit later on, how a completely theoretically normal cornea, you can see a blob of pigment in the middle, and that can actually be when you've had a, a perforation of the globe and the iris goes and plug that hole. There you're gonna be able to see an area of pigment on the cornea, and I promise I'll show you a picture in a few minutes.
And then we have proliferative disease, we could have limbal limbal melanocytomas or melanomas of the eye, which will show, which will appear as a, as a proliferative mass nodule on the eye, that will be pigmented. Of course, then we have neovascularization that we've discussed and when it's very, very, very pronounced, it looked like granulation tissue, and the differential diagnosis would be also neoplastic as those pictures of a squamous cell carcinoma that you've seen in the lecture before. And of course, all of those blood vessels and granulation tissue is gonna cause per se opacification.
It's gonna cause a pathology there. And lastly, we have infiltration of the cornea. We have fungal, bacterial keratiis, melting keratiis, which we'll see in a minute.
We can have abscesses, infiltration within the stroma that causes corneal opacities and also aerosinophilic caratitis, which is an immunemediated disease where the er aerosinophyll cells invade the cornea typically of cats and horses, and they will, Because corneal opacity, and we'll talk about corneal cytology and how to identify them later on. OK, so some, these were some of the key factors, dropping some information out there. And let's start seeing how the corneal, corneal ulcers heal.
So the superficial ulcers, those superficial ulcers are by definition, when only the epithelium is missing. So we have a completely healthy cornea and the one that we see in the picture, next to the picture which actually what's happening is that it is missing a piece of epithelium. And so what happens is that you can see actually corneal lima around it.
And when you use your fluorescent, which you should always use it in a red eye, painful eye, then it highlights that there's actually a lack of epithelium there. How is the healing process of these ulcers? Well, the limbus plays a very important role, and the limus is this this line normally darkly pigmented that separates the sclera from the cornea.
And that's where we have limbar stem cells. That's where when you've had, when a dog or a cat has a corneal injury, the whole cells which are here painted in green that will activate and will cause the epithelium to grow over. And what happens on the epithelium, getting a bit closer to that a more surface area is that the limal cells will make transform into the basal cells.
Of the epithelium and they are gonna start migrating to cover the stroma. So the aim is to cover that stroma that is being Exposed to the to the outside, because what happens is that the stroma can be invaded by bacteria, for example, very easily. So what the body has to do is to close that entrance, that potential entrance to pathogens, and that's the first thing that the cornea does.
They start moving those basal cells to cover that defect as soon as possible in this horizontal line, yeah. Once that happens, and these cells, these new cells are kind of set out and well attached to the, to the basal membrane here, then they start bringing up the rest of the keratocytes, or the, the cells in a more normal pattern until it reaches a normal level. Once the basal cells have been, have covered the whole area, at that stage, it will be flow negative.
You won't be able to see a fluorescent stain in that in that area anymore. So that, that would be our routine superficial ulcer. Now, let's go through another superficial ulcer, but it has very specific qualities or or changes that we see in our clinical examination.
And these are SATS, which stands for spontaneous chronic corneal epithelial defect. Because it's such a long name, we normally use the word scats, and it's what we used to call a box, a boxer ulcer or an indolent ulcer. And there's a slightly di differences with a routine superficial ulcer.
In dogs, and is that if you look, carefully to the picture that I'm showing, you can see the epithelialates there. Yeah, I'm trying to delineate with my, with my mouse, yeah, and you can see how you can see like a geographic a bit of a map, yeah, and you can see how I can delineate quite nicely the epithelium there. I've seen already this patient with fluorescent, and can you see that there's underrunning, the fluorescent goes up to there.
There shouldn't be fluorescent if the epithelium is healthy. What is telling me is that the fluorescent has underrun this epithelium. This epithelium is flopping, has loose edges, and this is a classical characteristic of of a skets.
And why does that happen? Why does the epithelium grow and does not attach to the surface of the cornea? Well, actually, in this patient on what happens is that you've got a what is called a yin, a cellular membrane on top of, of the Stroma of that ulcer, of the area of the ulcer.
And what happens is that when the when the limbal cells start to try and grow over, they cannot attach to the stroma because they have this the island membrane that stops them from doing. And what they do, they still will grow, the, the limbar cells are very stubborn and they continue growing. So there's gonna form an epithelium, but it's not gonna be able to be attached to the stroma.
The epithelium, however, because it's not anatomically correct, it, it has some of these plastic changes. So, what we do in these cases is to debride them. So we get rid of those epitheliums, flops, flopping, epithelium or loose edges, because it's not gonna be a healthy epithelium anyway, and then it can be bright the surface of, the ilium membrane.
So, The treatment for these guys is very varid and I'm sure you've all heard of them, and it comes from a very, A very simple procedure, which is a department with a cotton bud, which 65% of them will heal in 10 to 15 days with that procedure. Then we have a great keraotomy, which is a bit more invasive. And what I like to say here is that if you see the great keraotomies, You need to remember that the aim, the reason why you're doing this is to try and remove some of this is in membrane, and this is really, really thin.
You don't need, this actually is, is, they are, it's not even that big as I've drawn it here, but this is how deep you need to go. You don't need to go any deeper. You should actually not even see the line that you are drawing on the cornea with your great keraotomy.
So it's a very superficial terms that you need to do on those corneas. And when I say we're actually not doing them that often is because we've got the diamond vert prime and which is a, a small instrument that is used to, to the bride mechanically more aggressive than with a cotton but the base of the ulcer. And actually, there's an RBC study that has shown that with the diamond ver debride and you remove some of this is in membrane.
And actually the, the, the healing, success of this is free of 92%. So with the bit, you are getting an 85% after 7 to 50, 10 to 15 days, with a diamond where you get a bit of a higher healing rates. So this is the aim of this treatment or, or this procedure is to try and remove some of that in membrane.
But of course, just, we need to be very careful and we need to be sure that what we are dealing is aches ulcer and not deprive anything that is not aches. This is completely different than from cats. When you see a cats with loose epithelial edges, then a grid is completely contraindicated.
A diamond bird is completely contraindicated, and the rmen is controversial. Some, some ophthalmologists does it and some don't. But, in cats, these, these ulcers that have loose epithelial edges are generally secondary to herpes, so a completely other world, but they will look quite similar to what you see now.
But just remember a cat is not a small dog. Yes, we, we always say that, correct? So, with, those are how epithelial ulcers heal, so closing the surface.
Remember when you have the stroma exposed, when you have a corneal ulcer, always give an antibiotic, a broad spectrum antibiotic. I normally like to use isothery or With alvi, it's a once a day. This not tend to be non-infective, so you're just giving a, a, a, a broad spectrum antibiotic just to avoid infections, but you're not fighting an infection.
So you don't need a strong antibiotic for them. And then in 1015 days you be evaluate them and, and see whether they feel or not. If they haven't, you might have missed an ectopic or you might have missed a dry eye.
So, you might need to restart again with a concept, but it should be fairly easy to heal. Let's go now through stromal ulcers, which can be a bit more tricky. So when, when stromal ulcers are happening is that you, we've got a piece of a stroma missing and also the epithelium.
And there can be some superficial, so just a bit of the stroma is left or it can be quite deep nearly up to the senate. They can be complicated, so they can be infiltrated and have a lot of pus in them, which we see some pictures, they can be melting where the collagen as enzymes melt the corneal collagen and are cause a threat to the, to the structure of the eye. And what is key in these patients is to assess the depth rather than the diameter of the cornea, of the corneal ulcer, yeah.
So, knowing the diameter of the ulcer helps a lot, but what is most important is to know how deep that corneal ulcer is. And that's not an easy task, especially if you don't have a slit lamp, and sometimes if you have a slit lamp can be tricky, but, but we'll go through those in a minute. What is also very important is, to make an in-depth assessment of each individual case.
So I might not treat the same as superficial stromal ulcer, so, an eye that has some stroma left, but I have 70% of the cornea left. I might not treat it the same if it's a young dog, that is, if is a senile dog, because the healing capacities of a very young dog are much better and higher and faster than in an elderly patient. And the same for a patient that might have diabetes or Cushing's, which the healing process is quite compromising these patients.
So it's always good to, to approach its its case individually. So let's go through stromal ulcers, yeah. Either if there's a bit of stroma missing or a lot of stroma missing in that ulcer, what we need to do is that the stroma needs to become less infiltrated.
It has to become healthier. Yeah, and I'll show you a picture in a minute. Once that stroma has stabilised, and there's less infiltrate, then the epithelium will start growing over, yeah.
So, the same as in a superficial ulcer, the limbal cells on the limbus, the limbal stem cells in the limbus will activate and will start, sending all those cells to cover the stromal defect. Yeah. And that will be the first step once the stromal is less infiltrated and it's healthier.
So as soon as the healthier, the epithelium will be able to grow all the surface all over to cover the defect. And then the keratocytes within the stroma, which are these brown orangey clouds that I draw, then they will start to become activated and they will start building up the extracellular matrix. So the stromal thickness increases and the defect decreases and it will build in and in and in and then we have a less of a, of a Defect.
Now in very young patients, this filling in of the defect that the keratocytes can do might be much more efficient and it might need reach up to the normal length or width of the cornea. In elderly patients, we sometimes we may like the second picture here. They might not be able to fill in the gap as well.
So what you would see is a corneal defect that is true or negative and that it remains like that for the rest of the time of that talk. And we'll talk about the risks of this scenario, if, if you ever come across to it. So what happened with with this trauma ulcers as well, at the RBC we tend to manage them medically quite often.
But in general, the rule is that surgery can be justified when there's 50% of the defect or more. Medical management. So if you go for medical management, you require an in-depth knowledge of corneal healing and an excellent approach to cases.
Our, our patients that go medically so that we attend them medically, they go to our of intensive care and receive quite an in-depth medical management. If we have time we can go through it. And just to make you feel, this is not an easy task.
It takes years for our residents to feel confident to say whether they would take the patient to theatre or not. So it's not something that you can learn very quickly, but I'm hoping to give you some tips to make you feel a bit more confident confident on your decisions. So let's go through those trauma ulcers, yeah.
We've said we have these, these two pictures on your right-hand side, and these are probably clinical cases that you might see in your day to day basis. The one on the top is a pug, and these are classical ulcers that we see in dry-eye patients. It looks like someone has taken a punch biopsy.
Of part of a cornea of this dog, correct? And you can see how there's corneal edoema and the appearance overall is quite bluish, yeah. If you look at the picture below, it's a different patient and you can see how all of this area is infiltrated.
It's not a blue colour. It has like a yellow tint in it. So the, the, the characteristics of cholera is really important and sometimes that takes time to be able to see the differences, but I'm hoping with these two examples, it's quite clear.
So you can see this halo of blood vessels coming from the limbus, those machinery of blood vessels that the cornea builds 24 hours to, to build up and then a millimetre each day. So, you can see how this bluish aloe, I agree, that's corneal edoema, but the rest is infiltrate. And what we normally recommend when we see this type of infiltrate is to take a cytology.
Because that's gonna help us to decide whether we see lots of bacteria, whether we see lots of neutrophytes, whether we might even see fungi depending on the area where you work. So it gives us an idea of which pathology are we, are we dealing with, we might see lots of rods and that might be a pseudomonas, and this also could start melting in a minute. So it gives us some information and I think it's something that is easy to do.
And I, at the end of the lecture, so I'll give you some tips on how to do that. So this would be an example, this drawing, that I've made of the cornea would be a characteristic of the, the bottom picture. So there's a bit of stroma missing, not much.
In the picture above, there's much more, it goes to nearly deep stroma, that little crater, yeah. But in the drawing, what I show is that there's some neutroars, there's some bacteria which are Magnified for teaching purposes and some high faith, so you can see lots of pathology there. So what happens with those stromal ulcers that we've discussed briefly before, how do they heal?
So let's put this example of this picture. Yeah, we've got a pear-shaped corneal ulcer. We see that this stroma has been exposed because it's staining with fluorescent, and we see that this area where my mouth is a bit deep and this here, of course, it's already stained, but prior staining, it looked more yellowish.
It looked a bit more infiltrated. So let's see what does this dog to be able to heal this. So this was 36 hours after us starting treatment.
Do you see how the epithelium has grown over the defect? And now the area that is still flow positive is that area that was a bit more infiltrated, that is gonna take a bit longer until that stroma gets healthier for the epithelium to be able to grow over it. So you see how the epithelial cells have grown over.
They are still not causing, not closing the whole defect, but they are nearly there. Is going in the right direction. There's no more infiltrate.
There's not intraocular signs of disease. So it looks like this dog is able to heal with the medication we've we've started him with. This will be another example of an infiltrated ulcer.
And let me go through what I see in this picture, OK. So what I see is again a flu stained area, quite circular. And I can see and you need to trust me because you don't, haven't seen it before staining, sorry, is that there's quite a bit of infiltrate in this area.
And this area here, although it looks healthier, what actually happens is that it's deeper. So that can be also a red herring. If you have a lot of stroma like here.
What you see from the inside of the eyes, so the appearance of the eye is, you might not be able to see. But because if you have less trauma, less unhealthy stroma to see through, you might be able to see the interocular structures much better. So with that, we need to be careful.
But let's, let's We'll revise that in a minute, but let's go through the rest. So there's a bit of corneal edoema, but actually I can still see quite well the iris here, but I can see that there's a meiosis there. So probably this dog has what we call a reflexivitis when we have a very severe corneal ulcer and And there's a risk of corneal perforation.
The eye creates an what is called the reflex of secondary uveitis. So we will see a meiosis, we will see flare, we will see hypopion, so we'll see Intraocular changes that is telling me I'm not happy, this eye is not happy. I'm about to rupture.
Yes, so these are the ones that we need to take into, into into words for, for intensive care or to theatre. So this is the same I 48 hours after intensive medical management. So you can see how actually the ulcer went up to here and now we have this epithelium that has grown over that effect quite nicely.
Do you see this? This white structure, this is hypopion. If you go to the slide before, You don't see that hypopion here.
Always remember to pull the lower eyelid down to see if there's hypopion. If not, you will miss them, and that has happened to me. So make sure you pull the bottom down of the lid gently and you might be able to see hypopion on the ventral aspect.
This is pus in the eye and it's telling you there's a reflexitis so this eye is quite unhappy. So remember how I was saying in the picture before, how this area here, this hallows was quite infiltrated. The cornea has remodelled that and has get rid of that infiltrate and actually now there's a defect there of a stroma.
They're still staining with ferroane and this area is probably superficial stroma and this is deep stroma. But it's going in the right direction, it's healing nicely, so we'll continue with our medical management and you can see how different view of the picture, but how this This epithelium is growing over the defect more and more and that floor area is reducing and the inside of the eye, although in this picture, it's quite difficult for you to see, was also getting better. So those are little things that you can look for to see whether the, the cornea is healing in the right direction.
And this is, me drawing you what flu area was still positive because I had a, had a picture of, of the floor stain, but you can see how this cornea is looking healthier and healthier. It's fluoro negative apart from this part. And this was like around 45 days.
After the initial treatment, so it's all going in the right direction, and the dog is everyday more comfortable and so on. So they, they can be managed medically. It's just that you need to be very, very, very confident in, in what you're seeing and that what you're seeing is the right thing that should be happening.
So let's go through melting ulcers. The first melting, the first thing that needs to happen is for the melting process to stop. Like we said, the stroma needs to get healthier.
If not the epithelium won't be able to grow over it. And what you'll see, especially if you have a little la or some sort of magnification, is that that stroma will organise like in, onion layers. It looks like a, a layered stroma.
And sometimes depending on how the lights hits the eye, you might be able to see those lines and hopefully we'll be able to see that in some of the pictures. Once the stroma has become healthier, then the epithelium will be able to grow over it. So this is a picture of the melting, and a melting ulcers, a quite focalized axial corneal melting ulcer.
And how you can see them is, of course, with a picture, it is more difficult, but when this dog blinks, all of this whitish mesh of tissue moves around and that is straight diagnosis of a melting ulcer. And melting ulcers can either be infective or so aseptic with rods or with coca, or they can be actually aseptic. So that's when again, the corneal cytology might help you to identify whether the bacteria play an important role on them or not.
Certainly, you'll see neutrophiles, you, you'll see, you might see bacteria, you might see hyphae of fungal. In, in England, it depends on the area and at the time of the year, you might be able to see them. They are not super common, but, it's good to be ready for them, or at least be able to identify them.
And this is how a decimatocele would look. Actually, the decimatocele as, as, remember I mentioned before, how the area that is deeper, it looks healthier because you can see more inside the eye. Of course, you're gonna be able to see more inside the eye when you have highly no.
That is hydrated because the the cement is gonna be transparent. So you can see really well inside the eye. You could potentially look at the fundus through this and not through the very edemato cornea.
So sometimes looking better doesn't mean that it's actually better, but of course, you'll be able to see the, this, like crater-looking lesion and, and remember that it's 500 microns, a healthy cornea. So, that's probably going way deep into, into the SMS. And again, what we said, the SME doesn't stain with fluorine.
So you might see that in this ulcer, for example, The edges of the crater stain, if it's a recent SMS and the base, if it's the SMS won't stain. What can happen is that you have a pool effect and it's when you're flushing out the fluorescence which you should always flush it out. You might get a pool of fluids, of fluorescent fluid in there.
So make sure when you have One of these crater-looking ulcers to try and gently flush away to make sure the flaw that you are seeing is not a full effect, but it's actually a true stain of tissue. So, so that's right. So we have these two axial decimatoceles, and, we have this one that is very round but has a little nose there, which, which of course, this is not something that we would deal medically, .
This eye or an eye with a decimatocele is being supported by a 7, 10 microns with the SMS membrane is 7 microns with, and then a bit of the the endothelium, sorry, 7 microns with, and the dese membrane had maybe 7 or 10 more. So you are really In front of a very, very, very fragile eye. So those are not candidates for medical management unless systemically they are unwell, of course.
And and yes, they can heal actually. But this is not the ideal scenario. So what can happen and we sometimes see this in elderly patients, is that they have a, a very deep corneal ulcer and that progresses.
But the eye is able to heal over it. And what you see in this picture or in this drawing is a decematoil that has been epithelialized. And in your right hand side is a histopathologic picture of exactly the same.
That is a cornea. That's the stroma, the epithelium over, all over the the edges of the crater, all over the decimet's membrane covering the whole defect. So truly, you could get a completely fluorescent negative decimatocele.
So this is just to say that fluorescente helps a lot, but you need to be able to interpret. If you see a Flu negative crater, it doesn't mean that it's not fragile that eye because this eye, that has epithelialized is not less fragile than when the the seme is exposed because mechanically has a very, very little strength. So this patient's sneezing potentially could lead to a globe rupture.
So that's why we need to take into account the whole pictures and not, not only rely on our fluorescent stain. And I think it's important to be aware of this. And it's not unusual to see elderly patients with stromal ulcers, mid stromal ulcers that have been there for ages, and yet it doesn't mean that we will do surgery in all of them, but I think it's important that the owners are aware that, that I might be, a fragile, a fragile eye for sure.
So let's say this one of these stromal larers keep progressing and it ends up with a perforation. So things to know is that perforations can be very painful. So when there's a dog or a cat that gets corneal perforation with a cornea that has been there for a few days and it progresses further, when it perforates, they normally scream.
So it's quite a painful scenario that we would like to avoid, of course. And what we see is that aqueous flows out of the, of the face. So our nurse described a lot of tearing and tearing with blood.
And what happens is that the inside of the eye will try and clot that hole, either with iris or either with a fibrine clot or sometimes with both. And the aim is to stop the fluid from coming out so the eye can get its normal, normal globus structure again. So it can refill again with acres, to get, to restore its normality basically.
So what we can see is that there's pigments, or iris, or yellow infiltrate that might be coming out of the defect, and I'll show you a picture in a second. If that is the case, we would withdraw all topical medications. Just because some drugs can be toxic in the inside of the eye.
So we would probably just go on systemics and give systemic anti-inflammatories and antibiotics. And this is when certainly referers should be considered a leaking eye is not an eye that can restore itself. So how do we look, how does it look like?
And remember how I said that you can see a blob of pigment in the middle of an otherwise healthy cornea at the very beginning. This is the example, yeah. This is also an example of someone that has not flushed out the fluoresce.
So in It makes it very difficult for us to evaluate intraocular structures. So always try and flush, flush out the fluorescent excess once you've stained it. And what we see here is actually a fairly relatively normal corneal ulcers with a black corneal, fairly healthy cornea, sorry, with this pigmented area.
That it's coming from nowhere. So we don't see any pigment around it. So the only way this pigment would come from is either from a neoplastic disease or most likely with the history of this patient is iris, is an iris prolapse.
So this is iris prolapse lugging the hole of the perforation. So not only the I can do that job. Remember the hypoion, the pus, cells that we were seeing on, on one of those patients, once the aques come out, sometimes this plaque of fibrin and inflammatory cells will go and plug it.
So this is what we are seeing here, that reflex UVIis that the eye was getting ready for has actually done its job because the fibrin and the process have managed to block. That hole. And again, you can see how there's corneal edoema, because there's this reflex uveitis that has damaged the endothelium and not only the corneal epithelium that is missing on that ulcer, but also the inflammation in the eye that is damaging the endothelium that is leading us to have corneal edoema.
So, let's go through some review and some tips. So the epithelial and limal cells, will move towards the defect within days and weeks. So that is quite a fast, healing process that happens if the stroma is healthy.
Now, when there's a stromal defect, the stromal keratocytes will get activated and they will fill in the stroma that is missing, but this takes weeks to months, and sometimes it doesn't happen at all in elderly patients. So the fastest thing that you need to assess when you are seeing a dog with a, a mid stromal or a superficial stromal ulcer is to see that that epithelium is growing over the defect. And then you see how that stromal defect is getting less and less.
So the stroma is filling in. Those keratocytes are doing the job of producing that extracellular matrix to fill in the defect. Deep defects or perforations need surgical intervention, especially in those patients that have compromised healing.
And in that, I would include those patients that have dry eye. Even a young dog that has had dry, dry eye for a long period of time doesn't have good capacities of healing. So probably it's gonna need surgery to help him heal.
Knowing the healing process of corneal ulcers can help you manage some patients and remember how to look for flare, which I'll show you in a minute. So look for inflammation in the, in the eyes, see there's hypopion but also look for flare and do corneal cytology that will help you a lot as well to manage your cases. So let's give, let's put you an example since we, I think we have a bit of time.
And if you see, let's go through. Sorry, I'm going back on purpose. Let's go through this one, OK?
So I see this patient, what am I gonna do? So these patients, this patient has had already atropine in my clinic. So there's already dilated pupil, but this patient came with a pinpoint pupil, a very meiotic pupil.
Which indicated me that there was a start of a reflex UVitis. What I did was take a cytology very gently. I would avoid the deeper areas which are the ones that look more normal, if you like, and I would try and get it from here, which looks like there's more tissue or here.
And just a little samples is enough and then you stay in it with ad quick and you look for it. For sure, you see lots of neutrophiles, but what I look is, do I see rods, which could be pseudomonas, could I see cocai? And depending on what I see, I might choose an antibiotic or another.
So my rule of thumb is if there's cocai. I would use l fennele, for example, that has a very good penetration, of the cornea, or, if I see rods, then I would probably be using exacin, which is a fluxacin or orthobramycin, which is Dorex. .
And for sure, these ulcers need serum, need topical serum because that's gonna stop your melting so your collagen as enzymes to be, to continue melting your cornea away and that is quite intensive. We normally do it every two hours, so an antibiotic. 1 hour, a sum another hour, an antibiotic 1 hour.
So we alternate hourly these drops. Now, if I don't see bacteria, which doesn't mean they are not there, but it's probably means that it's not the predominant cell that is causing the melting, then I might not give them as intensively and I will concentrate more on the serum. To stop those enzymes from breaking my cornea down.
So that's how the cytology will help you to tailor the treatment to that individual. So there's not a recipe for it's melting. I don't treat all melting is the same.
It depends a lot on the patient. And again, I will get atropine to provide cyclopplegia to help that I to be more comfortable and because it dilates the pupil, it's gonna reduce the risks of having posterior cymeia of the iris attaching to the lens, when there's CVI. So I hope that gives you like a broad view of how I treat ulcers, which was not the end of the lecture, but at least you've seen a, a, a little bit of a, of a hint of how we treat them at the RBC and let's go back through the tips that I wanted to show you.
So how do we look for flair and this will be to, to finalise and start with questions. So you don't need fancy equipment to look for flare, a direct ophthalmoscope, or a small in the smallest dot you have on the highest intensity, you bring the lights down and, and you don't use the ophthalmoscope if you look at the picture down on your right, with your eye here. You are the one taking the picture, yeah, so you are in that position, you Open the eye in one, with one hand and you, you put the ophthalmoscope very close to the eye.
And what you do is you try to see, and you will certainly see the dot or the line on the cornea reflected on the cornea and that's the first line and the second line you see it either on the lens or on the iris depending on if it's myoical or meteatic. And between these two lines, you should not see anything because the aques is optically inert. In this case, can you see how I can trace the two lines together?
That means that there is flare, OK. So in a normal patient, you see one dot here and one line on the cornea and one line on the lens, and between them, you are not able to see anything. When there's a patient with flare, you are able to link the two together, OK?
So that's an indication of flare. How do I do corneal cytology? So there's lots of instruments that you can use, at the RBC we use a lot of the cyto brushes.
They are very gently to the cornea and you get really nice cell morphology. I have sometimes used interdental brushes, the ones that you can get in pharmacy or in even in supermarkets. They are a bit more aggressive, so you need to be a bit more gentle, but actually they are smaller, so I think you can be much more accurate with your sampling with them.
And then, if you don't have those or you don't want to purchase those, You could use the end of a scalp, a scalpel blade. This is a kimura spatula, of course, you don't need to buy an instrument to do that, but just so you know, it exists. And then it's describes also to use a stick swabs or cotton buds, but the cellular yield of this is really poor, so I would not advise you to do that.
I have sometimes been very fragilized use it to take a sample of the discharges, if I'm worried that I might perforate the eye with my cytology. And then I would use one of these to a bit more than that. And how do I do it?
So with a brush, what is really important is that you just glide the, the brush over the slide. You don't mash it on the slide, because just You see how the, the brushes, the little hairs are not being smashed on the slide like here. And, and you just slide it really gently so you have a really nice cellular morphology.
If not, you'll break all the cells and you won't be able to see what's happening in that cornea. So those are kind of dos and don'ts for corneal cytology. And this is an exercise that I'm not sure if we have time, they can stop me if not.
This is not an easy task and you might want to do it afterwards and email me your responses, and you probably have your answers already on your, on your slides, but it's just to see if you are able to identify the progression of this ulcer and how, actually this ulcer we managed to heal it medically, . And how are those steps, and, let's see if you want, I'll go through them, yeah, because I think it might be a bit tricky after all the information I, I vomited, but to you guys, but, and it's just interesting to see how a horrendous answer which is how we saw it is this one, the one bottom left, B1. And the exercise that I wanted you to do, guys, is to follow the next ones in a, in a chronological way, yeah, getting better and better and better.
Let's me, yeah, let's go through them, yeah. So the first one is B1. Yeah, that's the start.
The second one is C2, and it's all very subjective, but you can see there's less corneal edoema. The, the cornea looks less, less edematose. There's a bit less infiltrate.
This step is probably the most difficult one, but let's go through the third one. You can see how, there's even less corneal edoema, and you can see how the epithelium there where my mouth is starting to grow. And it's getting further into the stroma.
And the next one, which is E4, you can see how the epithelium continues growing and growing and there's less less corneal edoema. So the area of fluorescing is getting smaller. The hypopion remains the same, it's not worse.
And then the last one, which is not a flu stain picture, but you can see the edge of the epithelium as I, as I am following it around. So certainly a much smaller diameter corneal ulcer and again less corneal ulcer corneal edoema, sorry. So this is kind of a progress, it's probably quite hard one, a difficult one, but you can see how following them and certainly taking pictures can help you to monitor corneal ulcers.
And this patient, of course, was hospitalised with highly intensive medication and for systemic reasons, we couldn't anaesthetize him. So we managed well medically, luckily. But that's not always the case.
So, let's see this picture and you can see how there's this traumal ulcer that is a bit infiltrated. You cannot see it now because it's already stained, so always as since that, since that before. You can see there's a hint of hypopion there and diffuse corneal edoema everywhere.
This was 24 hours after intensive medical management. What's that hypoium? How much more hypopion there is there despite our treatment.
How much more corneal edoema is there despite our intensive intensive management, and you can see how the corneal ulcer is much, much larger and also deeper here. So, of course, medical management is not for everyone and in this patient, we have to put an amnion graft to close that hole. .
But sometimes we can, we can manage them medically. We normally give you 24 hours. If there's improvement, then we're happy.
If not, we'll probably go ahead for surgery. So a lot of information that I've delivered here, which is maybe a bit new to the ones that have just started, but I hope it's gonna help you to with your clinical decisions and your patients. And I'll be happy to answer any questions that you might have and also email me if you need to clarify some.
Thank you so much for listening. Thank you very much Marianne. I think that was a really excellent talk and particularly all of those, practical tips at the end were really helpful so thank you very much.
We have got, we have got kind of 5 minutes or so for questions at the end and we have been sent to you through. So, if you're happy to answer those, . Oh got one to keep with the practical theme, someone's asked when you would use serum drops and how you, how you actually make them.
OK. So serum drop, we at the RSC we have our blood donor programme, so we get blood donors to come to us, and those patients that cannot give a full Those for transfusions are used or it depends on each patient, but the blood work, the blood donor team will decide and will take maybe less blood volume from a donor for us to do serum. And we are very simple doing it.
So we, we just basically take blood, spin it down, and we store it in A little Eppendorf tubes, which are those tubes that have like a cone shape that are like 2 centimetre wide and we freeze them, yeah. It's, it keeps, its properties quite well when they, they are rest in, in the freezer. As soon as you defrost them, every time it's not in the fridge, they will lose properties.
And because there are no preservatives in them, it's a highly It's very easy that it gets infected and you have a, a cultural growth in there of bacteria. So that's why we use quite a small volumes, recipients of small volumes because we discard them nearly every day. You use them a lot when you are treating intensively, but we just want to be on the safe side to make sure it doesn't get infected and we're not putting more bacteria in an ulcer than, than not.
So we don't add anything else, we just use serum, 100% serum, . And the other question of when do we use them, I guess there is no contraindication on when to use it. You could, there's no ulcer that would not benefit from serum, I guess, but those that are indicated are mainly melting ulcers, for sure, and stromal ulcers.
And for me, any ulcer in a dry-ey patient, so a patient that cannot provide with a tear film, . I would add 0. So an example, a, a dog that comes to your practise with 5 millimetre chert test readings and a superficial ulcer.
The tears bring nourishment to the cornea, so the cornea can heal. If there's no tears or very few tears, that ulcer is going to take ages or, or might not even be able to heal. So you're giving serum, you're providing it with nourishment so the ulcer can heal.
I, I am super against those lubricants that are called tear, artificial tears. I hate the word artificial tears. There's no artificial tears.
They don't exist. They are just lubricants. OK.
So, there's no fancy drugs that will help, healing the cornea. You, you just really need serum and help that patient for that. But there's no fancy, drops that will, miraculously, heal a cornea.
Hopefully you can answer the question, yeah. Yeah, I think so. That was really good.
And another question that's been asked by Caroline is, with those the ones with the stromal ulcer and hypoium, how long do you take, you expect that to take to heal up for the hypoium to resolve? OK. So, you still see my screen, correct?
Can, can you, can, yes, perfect. OK, so, let's, let's say an example for the, in this case, yeah, this ulcer that I've seen, showing you the progression every 24, 48 hours. So you can see how there's still quite a lot of hypopion for the first few days, but this one, which I think there were 2 days between these two.
The hypopion, you can hardly see it here anymore. So I wouldn't expect the hypopion to go in 24 hours, but I would give it at least 3 or 4 days. Of course, it depends on how much there is, but I would say that probably I would expect this hypopion within 5 to 7 days to be gone.
OK, excellent, thank you. We've got a couple of questions about antibiotics use Eileen has asked whether you ever need to use systemic antibiotics as well as topical antibiotics or if you always just stick to topical antibiotics. OK, I'm very keen on treating topically and avoiding treating systemically.
I don't like to affect the rest of the system of my patients if I can avoid it now. So having said that, there There are some articles, some published articles that talk about the benefits of using doxycycline systemically and this is not because of its antibiotic properties. This is because doxycycline has some anti-PMM effects which is PMMs are metalloprotease as some of the enzymes that break down the cornea.
So the doxycycline appears to have some benefits to stop those enzymes happening. And actually we've seen in some research that doxycycline is excreted by the Mabomian glands, which means that it reaches the tar film. So sometimes in, in very specific cases, we might use doxycycline orally at the normal dose, 10 makes per k SIV or 5 BIV.
Just for the anti-methalloprotease, properties, not for the antibiotic properties, if that makes sense. Now, if, if there is a perforation, then for sure, I will be using cephalexin or amoxicla to protect the intraocular structures, that's for sure. Perfect, thank you.
Just one last question for you, because two people have asked about Remend, the, the brand of gel, so just wondered what your, what you thought about Remend, and whether that is suitable as an alternative to serum drops. The answer is no, categorically no. Reman has been marketed extremely well by the pharmaceuticals companies, and, I am, I've seen a few disa or a handful or more than a handful of disasters with women.
So, not because Ri is not good, it's just that I think it's being marketed as an the amazing, wonderful drug that I was mentioning before, trying to avoid the brand name. But, women. Has still not been shown to heal the cornea or has a wonderful characteristic of healing.
I think it's it's a marketing success, but not an after success. So I think truly, The agreement for me is an a lubricant and is not an artificial tear. So, that's why I think we need to be careful with how we call things and I, I, I think that's probably a, a place for remand, but it's not how it's been marketed, at least not in my experience.
And, and another thing to add is that it's a really expensive drug. So I think I, I don't see the benefits of using it. I don't use it at all.
Thank you, sorry to give you a political hot potato there at the end. I think, I think, I think we've run over, very slightly, so, we'll call it a day there, but thank you again very much. It's not your, it's not your fault.
We kept asking you questions, so thank you, thank, thank you very much, Marianne for an excellent, presentation, and, thank you to everyone who's been, listening. I hope you enjoy the rest of virtual congress.