Description

During the webinar, there will be a basic overview of what a corneal ulcer is and its diagnosis. The pathogenesis and consequences of corneal melting (keratomalacia) will be discussed. The medical management of keratomalacia will be described with advice on antibiotic selection, the use of anti-collagenases with discussion on the pros and cons of different ones, and management of predisposing factors. Surgical options and more advanced treatments will be outlined with advice on when it is most appropriate to refer.
 
This webinar is kindly brought you by TVM.

Transcription

Hello, my name is Helen. I'm the technical vet at TBM UK and I'd like to just steal 5 minutes of your time before David's talk to introduce you to a very exciting new product that we have joining our Corneal focus range later on this month called Strames. So strays is the first and only licenced product for the supportive treatment of corneal ulcers in dogs and cats.
It contains an acetylcysteine and it's an off the shelf anticalaginase eyedrop. There are many benefits to having a ready-made antilagenase product on your shelf. We know that homemade products can often be time consuming to prepare, they can often require a fridge or freezer storage, and they generally involve drawing blood from either a patient or a donor, which can obviously cause, you know, patient stress, etc.
We also need to be mindful that there can be microbial contamination of these homemade preparations if they're not stored or used correctly by pet owners. Stoney's offers a convenient alternative that saves time and stress for all involved, and as a bonus, has a long and open shelf life of 3 years with no fridge storage required. The licence dose is 3 to 4 times a day into the affected eye.
So an acetylcysteine or NAC for short, is a potent anti-allagenase, so it's really useful when we're concerned about protease and colagenase activity in corneal ulceration. So MMPs are protease and colagenase enzymes, so they're secreted from host cells, but also from invading bacterial species during corneal ulceration. They normally sit in a nice balance with colagenase inhibitors, but when they're secreted in excess, which can occur during any ocular surface disease, including corneal ulceration, they can then overwhelm these inhibitors, which leads to the destruction of that cornea and stromal caladinolysis or corneal melting.
And this is really a disaster that we all want to avoid, known as a melting ulcer. So adding in stromies as an adjunctive treatment is crucially important in cases of melting ulceration to try and help reverse this MMP attack. But we also should give consideration to using stromme preemptively in maybe what might seem a seemingly simple ulcer that is at high risk of melting.
So brachycephalic pets or those who got preexisting ocular surface disorders. NA also has mucolytic properties, so it helps to thin the mucus from the eye, aiding its removal. And thick mucus around the eye could be really uncomfortable for a patient and access anitis for infection.
It also has additional antioxidant and anti-inflammatory properties which can aid corneal healing. So straymes is a new addition in our corneal focus range, which includes various products that support corneal health alongside in practise educational tools and resources. More information about any of our products and services can be found on our website, or alternatively, please contact us by phone or email, we're always happy to talk.
And I really hope that you enjoy today's presentation and I'll pass you over to David. Hello, my name's Vicky and I'm head of memberships here at the webinar vet. Thank you for joining us today at this lunchtime webinar, Melting Ulcers, how to recognise and manage them.
As you can just see, the webinar has been very kindly sponsored by TM, so it's a huge thank you to them. Today we have the privilege of David Nut Brown Hughes as our speaker. David is an ophthalmologist and clinical director at Rural Referrals in Bristol.
He qualified from Bristol Vet School in 1995 and has gained his RCVS certificate in veterinary ophthalmology in 2004. Before joining Rural Referrals in 2012, David had worked in both mixed and small animal practises. His general practise background gives him a pragmatic and practical approach.
David has been recognised as a clinical teacher at Bristol Vet School and he's on the committee of the British Association of Veterinary Ophthalmologists. If anyone has any questions today as we go along, please just pop them in the chat box at the bottom and we'll come to them at the end of the session. It's over to you, David.
Hi there, so, I'm, I'm David. I'm one of a team of ophthalmologists at Ro Referrals, in Bristol, and obviously I'm here to talk about melting ulcers today. I think before we get going, it's good just to remind ourselves what the structure of the cornea is all about and what it's like.
So the bulk of the cornea is, is made up of the corneal stroma, which is layers of collagen, sort of layered in a very organised fashion. Which is what gives the cornea its transparent appearance. And on top of that, on the outer surface of it is the corneal epithelium, which is a stratified epithelium.
It's, it's adhered to the corneal stroma by a basement membrane, and I think that has clinical importance because it's problems with that basement membrane that causes indolent ulcers or scares or boxer ulcers, different names for the same thing. The inner surface of the stroma er it is, it is where we find the endothelium, and the endothelium's job in life is to keep the cor cornea stroma dehydrated, to keep those layers of collagen in an organised fashion. It's a bit like I always.
Think of it as like having a paperback book with nice pages on top of each other. But if you get it wet and you drop it in the bath, then the, the, the, the pages become all wibbly wobbly, and it's the same with the cornea. If, if that system breaks down, the lead structure breaks down and you get acity of the cornea, corneal edoema.
And whenever you talk about corneas, it's always worth remembering that the tear film is really part and parcel of the cornea. There's a really tight interaction between the tear film and the cornea. At the glycocalyx, the, the sort of, inner surface of the tear film where, mutants attach the tear film in a purposeful fashion to the cornea.
So, and then the tear film has its own structure, sort of lipid outer layer, then an aqueous mid layer. So what is a corneal ulcer? So any loss of corneal tissue is a corneal ulcer.
So that's a really broad brush. It could be a like a superficial ulcer, like we can see in this cat on the top photograph, or it can be a really deep right the way down to Des May's membrane. Her situation, really sight threatening, eye threatening situation like we've got in this pug at the bottom.
And what are the clinical signs? So usually corneal ulcers are painful. If you've got a painful eye then then sort of top of the list probably has to be a corneal ulcer.
So when we talk about ocular pain, we talk about the triad of ocular pain, which is really plethrospasm, so we've got a squinty eye, larymation, which is a watery eye, and then we would expect a painful eye to generally have a meiotic pupil. So if we've got an ulcerated eye where there isn't increasedlach cremation, where perhaps we do a Sherman tear test and and the the tear production's normal, then that should ring alarm bells because we would expect it to be elevated. And then you can get other perhaps more non-specific signs like conjunctivitis.
So when we say conjunctivitis, we really mean conjuncti for hypeaemia and perhaps chemosis, swelling of the conjunctiva, and we might have, for example, a change in the transparency of the cornea, like this ug on the bottom photo. There's this corneal edoema where the endothelium presumably is, is not able to cope with that water ression to the cornea. And as a general rule, ulcers stain with fluorozine.
But beware of the ulcer that doesn't stain with fluorozine because Desma's membrane doesn't stain with fluorozine. So if you have a sort of rim of fluorozine staining around an ulcer and a non staining centre, then again that should ring alarm bells. So if we see an ulcer, we need to sort of remember that an ulcer.
In effect, is a symptom, not a diagnosis. And so when we see an ulcer, you need to be thinking about like what's the cause of this ulcer? How deep is it?
Is there an infection? Is the corneal melting, which obviously we're gonna talk about lots as we go on, and is there any other disease? Is there dry eye going on?
Is there entropion, is there dyticiasis or whatever. So really, when you see a corneal ulcer, that shouldn't be the end of it, that should be the beginning. You need to get your detective head on and try and work out what the cause is.
And there's lots of causes, so, the simplest situation is that there's a trauma. The dog runs into a bush, scratches his eye, and gets an ulcer, or the owner shampooing the dog and gets some shampoo in the eye. But there can be sort of other traumas such as trichosis, so that's rubbing hairs.
It could be a Pekinese with a huge great skin fold rubbing the cornea, er, or it could be entropion or an ectopic cilia. And then I think particularly the last few weeks with brachycephalics and pugs being in the news so much over the past week or so, we need to remember that these corneas in the brachycephalic dogs are under sort of metabolic stress. The, the tears provide most of the nutrition for the cornea.
And, and so if you've got poor quality tear film or poor confirmation, then that cornea is just asking to have a corneal ulcer. And then there are other causes. Whatever your mnemonic that you use, or we, we were always taught to use vitamin D or damage when I was training, but you need to kind of go through that process and just go through the checklist of possible causes.
And I often think it's really worth really accurately describing what you see with a corneal ulcer because by doing that, you might well er get your diagnosis too. So think about the shape and the position of the ulcer. Is it, is it a sort of dorsal ulcer right underneath the upper eyelid?
Because that could give you a clue to perhaps there being an eyelid lesion that's causing an ulcer. Is it linear, is it dendritica, the multiple ulcers, and how deep is it? Is it, is it a superficial ulcer in a boxer dog which might sort of give you the, a clue that it's probably a scare, or, or is it a more deeper ulcer in a young dog just below the eyelid, which might make you think perhaps you need to be looking for an ectopic cilia.
So with your, when you've been a sort of detective, a corneal detective, then here's a sort of few things to think about as well. The first thing is make sure that there's a blink reflex. It's worth just quickly as part of your general examination, just quickly tapping the lateral and the medial campfi of an eye, just to check that there's a a blink there, cos obviously if you've got a facial paralysis, then that that could, that could be your answer, that could tell you why you've got a corneal ulcer.
And as I've already alluded to, a really important thing is just have a really careful check of the eyelids. So, in, in, in a young dog or an elderly cat, for example, there could be entropion, there, and sometimes, er, entropins are intermittent. It could be that you get an entropion when the, the, the head is in a particular position.
So, so, so have a look at from all sorts of different angles and all sorts of different positions. And if you've got a young dog and it's particularly painful, always remember that ectopic cilius like is at the bottom right of the screen. Can cause, can, can cause a really nasty corneal ulceration.
And also don't underestimate the power of an eyelid lump. I always, I always think of. The, the eyelids and the cornea a bit like the windscreen of a car, and if you had a leaf under your windscreen, you'd probably, a windscreen wiper, you'd probably stop the car and take the leaf out because it's, it's, it's, it's, it's annoying and, and it affects the way the windscreen's working.
And it's the same, it's the same with an eyelid on a cornea. And I kind of take this analogy a little further because the tears are a bit like the washer fluid in a in a in the in in the reservoir of your car and you need to think about the amount of tears, so sure if you run out of water in your washer fluid. You're gonna have problems keeping your windscreen clear.
But also remember that your washer fluid works better if you put that blue stuff that you buy from the garage, the, the additive in the reservoir. And I think that means you've got to have good quality washer fluid, and it's the same with eyes, you've got to have good quality tears. If you don't have good quality tears, then you can have plenty of them flowing in your eye.
You can have a normal Sherman tear test, but if there's some problem with the fats or the mucus in the tears, then. Then, then you can have problems. I think a telltale sign, if you're, if you're looking at an eye just across the room, if you see these sort of mucousy strands, you know, nearly every cavalier that I see has these mucousy mucousy strands, then to me that should just be a warning sign that there might be a a problem with the quality of the tears, and it's worth just sort of investigating what's best to do about that.
And it's also worth just checking that you can see a nice reflection of your fluorescent light or whatever lighting you've got in your consulting room on the cornea, because if you've got a disrupted reflection, then that's usually a sign that there's a problem with the corneal surface. You know, the corneal surface should be a nice refractive surface for clear, crisp vision. So if you're not getting a crisp, clear reflection, then that's a sign of trouble.
So there are a couple of really useful, simple things to do almost without thinking, as well as obviously doing your tear test. The other thing to do is just make sure you look from different angles. So here's a obviously a a very poorly cornea.
If you look at it, straight on, you can see that, that, you know, there's things going on. But if you actually take a, take a look at a photo from the side, you can see that the profile of that cornea is really, really changing. It's, it's, you know, it's, it's slumping down, heading south, it's like Homer Simpson's belly there, and that's because the, the sort of integrity of the cornea has been lost and gravity is, is, is, is, is pulling on that, on, on that corneal tissue and making it slump downwards.
When you're when you're assessing a cornea, it's really important to to have a, have a handle on how deep. An alter is if you can. I think, we, we have the luxury of, of having slit lamps and, and with a, with a slit beam, we, we, we kind of swing the slit beam across the cornea and, and we look at how that beam deviates as we go across a lesion.
So here's a beautiful photograph from, from, from one of my colleagues, at the clinic, Matt, who, who, who's managed to capture the slip beam, sort of getting a a lot thinner as it crosses this this matter seal here. So that's where As we do the examination, we move the beam of light across, across the ulcer, and you can see as the as the beam crosses the ulcer, you can see how it deviates and, and we can then assess how deep that ulcer is. It, it's the depth of an ulcer that really stresses us.
A large shallow ulcer is, is a nuisance and it's painful, but a small deep ulcer is gonna be much more sight threatening for the dog. Now obviously a lot of people don't have absolute lamps, you know, they're expensive bits of kit, but there are a few simple things that you can do and are worth just sort of getting in the habit of doing. So the first thing is if you've got an ophthalmoscope and it's actually working and it's actually got a battery in it and all those sort of things, then if you dial up 20, the plus 20 lens, then that's a 20 dapter lens that you can use to to magnify and get a closer look at the eyelids.
So, so it might be that you wonder whether there's an ectopic cilia there, while reaching for the ophthalmoscope on plus 20 is a useful thing to do. So you can see how on my laptop I'm able to magnify it. The logo on my laptop quite nicely.
And you can use an otoscope in the same way. I've got a kilo otoscope, which actually isn't isn't as helpful as perhaps the Welsh Allen one that I used to have, but if you have a go and use the sort of little lens that, that you use for your otoscope, then you might find that quite handy little magnifying glass. And then the other thing that we've all got in our pockets is, is a phone, so you could just take a photo and try zooming in.
So that's what I've done here, I've zoomed in on the, the photo on the left. You can see it, you do start to lose detail and does pixelate quite readily, but it can be, can be useful. The other thing for a couple of quid or, or, or certainly less than a fiver, you can buy these, these clip-on macro lenses that you can just get on eBay or Amazon or wherever and clip them onto your phone camera.
And then if you get a torch and illuminate from a different angle, you can then start to get a real appreciation of 3D by doing that. So here's, here's a picture of my the logo again on my. On my laptop and you can see that actually the Fink writing is, is below actually below some plastic and, and the oblique lighting is really showing up the dust that's on my laptop.
So, so actually using your camera taking a photo and then reviewing it is a really useful thing to start practising and thinking about doing. So here's an example, a good example of just sort of using a logical approach to corneal ulcer. So we've got a corneal ulcer here and you can see that it's, it looks quite shallow, but the fluorozine saying is very much associated with the third eyelid.
There's a, there's like a triangle, and the closer to the third eyelid, you get the wider the fluoroine area. So, so it's, it, it's, I've, I've highlighted it here with this triangular green. So what you need to do is basically read your cornea, think, well, what, what, what could be causing that?
And if you think logically, you think, well, maybe there's something underneath the third eyelid, and sure, when you lift the eyelid back, there's a lovely grass seed under there. So just by thinking logically about the, the ulcer and what you're seeing, you can often find the cause. But what we're really here to talk about today is, is, is is melting cornea, sort of keratomalacia.
And here we've got a melting ulcer in a cat and you think, well, look, there's some, there's some mucus on the on that lower eyelid. Well, that's not mucus, that's actually sort of melted corneal collagen that started to sort of slump down the eye. Onto the face, and it's a, it's a really serious, really sight threatening, problem, so, and, and it's one that we do commonly see.
So melting ulcers always start out small. And then they get, the process goes on and on and they get bigger and bigger and, and as the name suggests, they literally melt the cornea away. So here we've got 222 examples.
Apologies, they're they're not quite quite in focus, but the, the picture on the left you can see. There's, there's significant loss of, of, of, of corn cor the the corneal structure there. And if you look carefully, you can see that there's some hypo, some pus inside the eye ventrally.
And on the picture on the right, again, you've got complete loss of the corneal structure on that melting area. The, the cornea is literally liquefying and you can see that there there is probably corneal collagen getting stuck to the eyelids on that, on that French bulldog. So when you get these melting ulcers, I think there's a few things that you, you, you, you, kind of need to ring alarm bells.
I mean, seeing a corneal melt should ring an alarm bell in its own. Own right, really, but if you see these things, then you need to be really, really worried. I think the first thing to be concerned about is if you get an ulcer, and you start thinking that the cornea is beginning to look clear.
Well, remember that's probably because there isn't any cornea anymore. So in the picture on the left, I, I, with, with, with the IFA you can probably imagine that there's a, there's a, there's a pupil behind that cloudy cornea. In the centre of the ulcer, and that's a, that's a bad sign, that basically means the whole of that cornea has gone and we're literally looking straight into the eye.
And when the eye ruptures, this is the sort of appearance that you get. We've we've got a large central corneal ulcer here and then and then then a hole that's plugged with fibrin and blood and probably a bit of iris tissue. It's a disastrous situation for an I to let that happen.
A couple of other warning signs, as I mentioned on the, a photo, a couple of slides back, if you, if you see hypoium, if you see pus in the eye, then that, that really worries me as well, because that's a sign that this inflammatory mediators actually inside the eye. The mediators aren't just sitting happily on the surface of the cornea. They've got, they, they, they, there's an inflammatory process happening right close to the inside of the eye, which tells me that there's, there's, there's deep down action and, and, and, and we shouldn't ignore that.
The other thing to be on the lookout for, would be high femur. So the iris kind of naturally wants to bleed. It's kind of, it, it, it, it, the only thing that stops an iris bleeding is really the intraocular pressure, the pressure of the areas and I guess the vitreous pressing on it, stopping.
Leaking out of those blood vessels. So if you get high femur or blood in the eye and there's an ulcer, then that tells me that there probably has been a collapse of the eye, that the eye has perforated, because there, there would have been a sudden drop in pressure and that means that the corneal blood vessels can start bleeding. So if you see high femur, that, that's of concern.
The other time you might see that is if there's been a puncture wound again where there's been a sudden collapse of the eye, maybe the fall has, has left, has left the eye. been and gone, but the high femur tells you that there has been a, been a rupture. And I guess like anywhere in the body, if you see something greeny yellow, it, it, it, it, it's usually a bad sign, so it's, if you see a greeny yellow rim to an ulcer, that tells me that it's infiltrated and it's, it's that there could well be infection or there could well be a significant inflammatory process going on with lots of lots of neutrophils.
So even if it's a small ulcer, if you're seeing a yellowy green sort of sort of corneal tissue around it, then that should ring an alarm bell. And the other thing you often see, you often see this in in corneal melts that that have healed, perhaps you had a small focal corneal melt that's self resolved, but when you look at it under magnification, you can see concentric circles going deeper and deeper into the cornea. And I think that's a bit like the rings on a tree or or an oyster shell type.
Pattern as, as, as the, as the cornea melts inwards and, and more and more lamellae are destroyed, you get these concentric circles of corneal melt. And that's a brilliant example in this photo of, of corneal clarity. That, that, that's an eye that really is about to, to rupture because you can, you can almost, you can see that you almost see the fundus quite clearly through that perilously thin cornea.
And I think if you're thinking, is this also melting or isn't it, you know, should I be worried? I think it's always safest to be worried. So there's 48 hours between these pictures, so, so the eye, the eye I've just shown you in the previous slide on the left is how this eye looked two days before.
That's a photo from an advice email that came in, and, and then two days later when we actually, when we actually saw the eye, things, things had sort of progressed significantly. So, if, if, if you see an eye and you're worried, we're obviously going to be talking about the, treat what what treatments to give and what's available, but it's best to overreact and be, be aggressive in your treatment to try and stop this, this sort of situation progressing. So there are certain, there are certain risk factors.
I think the one that's, that's, that's really current is the whole confirmation problem. I mean, if you, if you look at this Japanese chin, you can see plugs of hair all sort of stuck horizontally on, on the centre of the cornea. And, and they're stuck there because those eyelids haven't been there for months.
Those eyelids can't close over that eye. There's no way that those eyelids can act like an efficient windscreen wiper over, over the windscreen. There's incomplete, there's incomplete blinks, there's corneal exposure, it's probably got dry eye, and even if there were tears, those.
Those lids, there's no way that those lids are able to distribute tears, and remember tears provide all the nutrition to a cornea. There's no way that that cornea can be healthy. So in the bracketcephalic, it it it it's, it's just a, a disaster waiting to happen, you know, they have poor corneal sanitation, they tend to have poor tier quality, poor blink rates, incomplete brinks, it's, it's, it's just asking for trouble, as, as, as unfortunately we all probably know.
I mean, the main thing that you can do for these guys, is a medial the sort of go to thing that we use is a medial camproplasty. So this is a sort of immediately pre-op and an immediately post-op picture of a, of a pug who's had, who, who's had camproplasty and, and actually a lower lid hot Celsius procedure as well. But I think cosmetically, to me, cosmetically, the postoperative appearance is, is much nicer and hopefully those, those corneas are gonna be much better protected and .
And, and, much less likely to get a corneal ulcer. And that's the plan. I mean the poor dog, you can see he's got his tongue out because he's gasping for breath, so we've sorted his eyes, but he's got all these other problems as well.
There's things that we can do that cause problems, so it I think most people are aware that steroids do predispose to corneal ulcers, so that's, that's topical steroids in particular. So, if you've got a sore eye and you're not really sure what's going on, then before you reach for the steroids, just always remember that you might be making a small ulcer that you perhaps haven't noticed worse. The other, the other thing to bear in mind is topical non-steroidals aren't .
Particularly kind to corneas as well, they're pretty epitheliotoxic, so I think just remember that that any topical potentially can cause, could cause issues and just before you before you use some of these drugs, just go through a thought process, a sort of a cost benefit analysis if you like, of what you're using. The other thing where we commonly see corneas run into trouble with corneal melting is, is sort of indolent ulcers or box with ulcers or skeds is their correct name, spontaneous chronic corneal epithelial defects. And these are the sort of underrun ulcers that you see, and I think everyone's very good at staining an iron and realising that the fluorozine is underrunning a sort of corneal epithelial lip at the edge of the ulcer.
And I think of this as like the, the corneal epithelium being like flaky paint on a door, and actually to get this problem fixed you need to do some decor decoration preparation. So whether that's sanding down the wood or even planing down the wood with a superficial chaotectomy, to me, these are often really a surgical problem. But you need to be careful that you are indeed treating a scared and not a superficial ulcer that's happened for some other reason.
So we're particularly nervous when we're sort of treating ulcers that look like this in the brachiocephalic. And the procedures that get talked about for these keratoomies, whether it's a grid keraotomy, a diamond bear or a puncate keraotomy, they are specifically aimed at treating these treating scads. So, like I was saying earlier on, there's there's a specific problem with the basement membrane of the epithelium.
There's poor adherence and so the keratotomies are aimed at increasing that adherence. Then, a grid keraotomy or a diamond bear or any of the procedures, aimed at treating scads are certainly not to be used on streal ulcers. If there's any streamal involvement at all, they're not, they're not the thing to go ahead with.
So, a lot of practises now have diamond bears, quite rightly, cos you can treat, indolent ulcers or scareds er in conscious dogs. With, with a diamond bear, but just remember it's not a safe process. It, it, it, it usually is, but in one study, 13 out of 341 dogs develop keratomalacia after diamond burring, so we're really careful, we treat these aggressively and we're very careful with the hygiene of our diamond birr between uses.
My, my go to, surgery for a scare is a grid keraotomy. But you can have problems with a grid keraotomy. So here's a, here's a, a postoperative, photograph of, a grid keraotomy, and you can see there's, there's, there's trouble, with this cornea.
We've got quite significant corneal melting. Now that eye, did resolve, but it, and heal up, and we, you know, there was good vision, you could see a pupil, we can see into the eye and the and the doctor could see out, but it was harder work than we were hoping for. And here's another example, this, this was a case that had had a, a grid keratotomy in practise and, and some of the the score lines had melted and, and, and, and the significant corneal loss there.
So if we do a keratotomy, then we, we treat them aggressively. We assume that they're gonna develop a corneal melt, beforehand and treat them as we're going to discuss sort of almost prophylactically to try and prevent er these problems happening. So what's actually going on with a corneum out of keratomalacia?
So it's not rocket science, and I, I, I just try and simplify everything down so it's logical because I'm. Kind of quite simple, so I like to keep things quite simple so. The, the corneal stream is made of collagen, so if you're getting an ulcer, there must be loss of corneal corneal collagen.
And we're dealing with nature, so the thing that gets rid of stuff in nature are are are enzymes. So if we've got collagen being broken down, we must have enzymes at work, there must be collagenases present. And there, there are various enzymes in that that that that can affect the cornea, various proteolytic enzymes.
So for example, the serum proteinases which are produced by macrophages and and neutrophils. But the ones we're particularly interested in, as Helen mentioned in her talk, is it the MMPs, matrix metalla proteases, and the two we're particularly interested in are called MMP2 and MMP 9. There there's, there's MMP one, and, and so on, but the, the ones we're interested at MMMP2 and MMP 9, and metalloproteases, MMPs, which is what I tend to call them, are, are, are proteases, pepidases, but they, they have metal ions as cofactors, so usually calcium and zinc, and they have the ability to degrade the extracellular matrix.
And they're not just found in the cornea, they were originally discovered, I believe, in tadpole tails. So again, a similar situation, tadpoles turn into frogs, which means some collagen must be got rid of, which means that there must be colagenasis there. But they're also important in the pathogenesis of arthritis, in neoplasia, you know, metastasis, there has to be changes going on in the extracellular environment for metastasis to happen and MMPs are involved in that.
But they also have a normal role, like, with all, all things in the body, there's a kind of a turnover of tissue, so it's normal for corneal tissue to be destroyed and replaced as part of normal housekeeping. And it's, it's MMP2 that is, is that sort of housekeeping enzyme. It's MMP2 that's kind of produced by corneal curatocytes and, and, and is, is the sort of, kind of wear and repair, wear and repair, kind of, kind of enzyme.
And then MMP 9 is, is, is produced much more in response to corneal wounding. There's, there's the flip side. So in tissue there are inhibitors of MMP, so, so there are these guys called tissue inhibitors of metallo matrix metalloproteases, and then there's alpha 2 macroglobulin, that that inhibits, glainase.
And also there's not like a constant production of MMP MMPs, the, you know, the, the, the genes for MMPs are switched on and off as appropriate, so there is, there is some, some gene expression control going on. You can also get exogenous MMPs so, so we've talked really about MMPs from in the body, er, from within the cornea, but also you can have other sources and the classic source would be from bacteria. And if you look at MMP levels in ulcerated eyes, ulcerated eyes have higher levels of proteolytic activity, and then this, these, these increased levels decrease as the cornea heals.
So if you have there's been. Studies where there's been MMP levels compared between a normal eye and ulcerated eye, and you can document that difference or rise and then fall back to normal. And if that didn't happen, then you're gonna get corneal melt because because the MMP levels are gonna be high and inappropriate.
So we've kind of got like a, a sort of homeostasis, corneal homeostasis where, where these enzymes can perform their sort of housekeeping roles without getting out of hand, and it's like a balancing act between the inhibitors of the. And of the enzymes and the enzymes themselves. And then we've got these contributing factors like dry eye or corneal exposure or bacteria or, or, or, or some steroids going into the cornea that can tip the balance in favour of the MMPs and we might get a corneal melt.
So it's, I find it quite useful to think of it as a sort of homeostatic situation. So, how do we manage these cases? Now, like with a lot of things in veterinary medicine, you know, we, we're desperately trying to be evidence based these days and there was a lovely review of all the treatment options of keratomalacia .
Written last year, but, but the clue to the problems in the title in that it says, including non-randomized controls and non-controlled studies. So we try and be as evidence-based as we can, but like all things in, in, in veterinary medicine, you know, we have to fill in the gap sometime. But why is, why is, why is good case management important?
Well, This was this was a card that I saw in our local card shop and, and I think it demonstrates quite nicely why case management is important because the model for this, this picture obviously it had two banks of poorly controlled car to Malaysia and lost both his eyes, you know, it's, it's a disease that we need to take really, really seriously. There's a couple of things, just common sense things to say before we sort of get into the nitty gritty, but remember these, these eyes are fragile, you know, very often there's just Des May's membrane, which is, I don't know, however vanishingly thin Desmay's membrane and an interthelium is holding that eye together. So just remember they're fragile, you know, if you, if you, if you start having a bit of rough and tumble with the, these guys to.
I don't know, for example, take a blood test, then that can finish the job off and you can rupture the eye. So it's worth just thinking outside of the box. So here's, here's a pug that I treated, actually a little while ago now, and he, he was a bit like a cat, he liked being wrapped up in a towel.
But some pugs prefer just being examined on their owner's shoulder or upside down. You need to think outside of the box, but sort of strong arm techniques just aren't appropriate, you know, they stress you up, they stress the dog up, they create phobic dogs, hedgeshy dogs, and, and, and, and that's not the way forward. Now, kind of as with most wings veterinary, there's various ways you can treat, you, you can treat melting ulcers.
There's there's. Medical, surgical, and the new kid on the block is cross-linking. So I guess the bulk of my talk really is gonna be about the medical management.
And I think the first thing to point out is all cases need medical management. Even if they go to surgery, you still need to be doing medical management because there's no point in doing an amazing corneal graft, repairing a corneal perforation if you then don't give any appropriate antibiotics and appropriate sort of adjunctive treatment. But there are, there are some cases where you can just treat them medically, and there have, there has been a, a couple of studies sort of looking at the success rate of medical only management.
And, and one study in 2020, found that 31 out of 57 cases treated with medical treatment only were successful. So that's. To me, it is a success rate, but it, it's by no means perfect.
In another study, in that study, in, in the second study they were comparing medically treated eyes with eyes that were treated with medical management in in conjunction with corneal cross-linking, and 9 out of 30 of the medically treated eyes needed some rescue. And, and they're also skewed populations, these, these, these studies didn't include desmatoceles or perforation, so the very, very deep ulcers weren't being included in the study because they, they weren't appropriate for medical management only. But you must remember that every case needs medical management.
And here's a case that we managed medically, it, it, this also looks a mess, but actually with a slitland examination, it was a very, very superficial corneal melt. I mean they were owners that literally lived practically next door to our surgery and they were, they were in quick as a flash. We were able to instigate appropriate medical management and we got successful treatment.
But as with most pug eyes, you once you get problems with the cornea, you get corneal pigmentation and, and so yes, we got healing, but we did get corneal pigmentation. And if you look carefully at the medial campus, you'll see that, that, that it's changed shape. They, they had a medial camproplasty as well.
So The first thing to think about with treatment is antibiotics and as I've already mentioned, the, the bacteria can be a source of MMPs and, and the normal kind of protective mechanisms of the cornea are damaged, if there's, you know, the epithelium and, and, and likely the tear film are there to protect the cornea. So, so if that's damaged, then we need to be thinking about antibiotics, but. You know, we need to be appropriate with our antibiotic stewardship, and, and we need to follow the cascade, you know, drugs don't get licences just willy-nilly.
They get licences because they're, they're good products and, and they're designed for the job. So, yes, you do have to go off Cascade sometimes, but it's always worth just going through a, why am I using this antibiotic, and is it the most appropriate and is it the most appropriate licenced product? I think it's, it's always good practise to go, go through that sort of thought process.
We do corneal sampling on pretty much all our ulcers, and I appreciate that's the benefit, you know, with the benefit of working in a referral practise. But certainly cytology is something that, that is, is, is, it can be a bit, bit of time to do, but it isn't costly to do. And it can give you the heads up of what's going on.
It could, if you're in doubt, if you're . Wondering whether an ulcer is about to melt, you could just do cytology and if you see a sea of neutrophils, then that, that, that, that, that might prompt you to, to kind of act differently. And you can also try and see bacteria on, on the samples and that.
Give you a clue as to what the most appropriate antibiotic pending culture is. But I think culture is really useful because we do see resistance. It's common, to all the antibiotics that you're likely to use.
We regularly see resistant, sensitivity profiles. So we, we take samples, you can use swabs, we use little dental, brushes like in the photograph or, or if appropriate and the eye is strong enough, then you can use yer brushes. And here's, here's some examples.
So on, on, on the left, here's a cytology sample and we can quite clearly see some rods shaped bacteria and in and indeed that we later went on to grow pseudomonas from this cornea. But we knew ahead of time that we had a, a probably a gramme negative rod and we were able to tailor our our treatment accordingly. And on the right, again this is from a a a severely nasty melting ulcer and and on cytology we were able to quite easily see these fungal hyphae and again we isolated Aspergillus from that eye and fungus can cause.
Really severe corneal inflammation and melting processes. Corneas don't like having fungus there at all. So finding that on cytology was able to give us the heads up right from the start that we needed to be really, really going at this, hard to, to, to get a cure.
And like I say, resistance is, is common, and with the isolates that we're likely to get the, the sensitivity profiles are likely to be different. You can use a a charcoal swab for your cultures, but, there was a, there was a little abstract, last year, suggesting that, E swabs might be a more appropriate, you know, the swabs that you break off into the liquid, might be more appropriate for corneal culture. And from corneal melting, the, the most common isolates, obviously you can isolate pretty much anything, in, you know, when you read these papers, there's a whole list, but the two common ones were pseudomonas, and beta hemolytic streptococcus, so they're gonna probably have very different sensitivity profiles.
But it's also worth remembering that a lot of these ulcers are sterile, you know, you, you, you've got MMPs, you don't have to have bacteria to have MMPs in your, in your, . In, in, in your cornea. And they say the paper, the recent paper from last year looking at this, er did comment that pseudomonas is bad news.
You, you're statistically more likely to end up with no I if you've got pseudomonas also there. So the antibiotics are available, so, first of all, fucidic acid, I think it's most vets in first opinion practises their, it's their go to, you know, it's a licenced product and it's, it's, it's for conjunctivitis and so on. But just, just remember that it is, it's activity is really only against gramme positive bacteria.
So, so if you're suspecting that there's a gramme negative or you don't know, then, then, then just go through that, that thought process. If we, if you've isolated a streptococcus and you know it's sensitive, absolutely, but just go through that thought process. And the same with the other licenced product, there's, there's a couple of gentamicin licenced products, it's a, it's a good bacterial yal anti antibiotic with excellent, .
Activity against gramme gramme negatives, the, the, the main concern with gentamicin with overuse is that it can be epithelial toxic and can delay, delay healing, but if you know you've got a pseudomonas, it might be that gentamicin is just the ticket and it and and as I say, it's licence. Off licence, a commonly used antibiotic is chloraphenacl, and I guess that's is probably our go to certainly prophylactic antibiotic, or, or, or based on sensitivity, you know, there's no reason why chlorophenacl can't be used against a staph or a strep, but it hasn't got activity against pseudomonas, but it's commonly used and and it's a good choice. And then there are the fluoroquinolones, so, so the one that we use in our practise is afoxacin oreoin, but it is a fluoro it is a fluoroquinolone and, and I think, more and more, everyone's increasingly aware about the whole bacterial stewardship thing.
It's bacterioidal this broad spectrum, it often has good activity against pseudomonas, although we do get resistance and again it has activity against staph and strep, again you get resistance. And the resistance patterns can be very, very different, so sometimes pending culture, if you've got a dire situation, then then we sometimes do use combinations of antibiotics until we've got results. So that's the antibiotics done, but what what about MMPs, you know, they're they're, I've kind of already alluded that they're the sort of big thing with corneal melting.
So like we were saying, if we don't get sort of rapid normalisation of MMPs then we're gonna get a corneal melt. And so one of the key objectives to treating a corneal ulcer has got to be getting that proteolytic activity back to normal. So we've got a few options there for doing that.
So as with treating anything, you need to get to the root cause. So if there's dry eye, remember to treat dry eye. If there's corneal exposure, think about a medial camproplasty.
If you think there's a an infective process on going on there, then, then identify the bacteria and treat them. A a bit like putting out a fire, you can, if you get rid of some of the melted cornea, so those early pictures with the slumping corneas, if you were to just kind of get rid of that slumping tissue, it's doing nothing, it's, it's not can't even support itself, let alone support the eye, then you're reducing the burden of MMPs on that cornea. So, so doing a keratectomy is a, is a useful thing.
Obviously you need to have magnification and and and sort of being in an appropriate setting to do that. But the flip side to the equation is we could increase the inhibitors that we could try and push down the right hand side of the balance in this, in this, this picture. And this is where your serum and your EDTA and your NAC and your tetracyclines come in.
So the common, the commoner, anti-alaginasis, as I say, in practise, is serum plasma, people talk about ETTA and, and obviously NAC, the sort of, well, it's not the new kid on the block, but it's, it's, it, it, it's there and then, and then there are other options as well. So if we just sort of go through the pros and cons of some of these, I, when I say serum, I kind of mean serum or plasma, and that's anti-alaginase. The main, the main anti-allagenase in serum, plasma is alpha 2 macroglobulin, but there are, there are also other goodies in serum.
I, and it, and it's very hard to know how important some of these things are, but there's immunoglobulins and there's growth factors and things like fibernectin, which are all good for healing. So how do we prepare serum or plasma? So the difference between the two is whether there's anticoagulant in there, obviously serum has no clotting factors because it's, it's clotted.
But we, we draw, blood tests usually from a big donor dog, put it in the, the brown serum tubes, put it in the centrifuge, and then we tip the resulting serum into drop bottles that we sterilise, and then we store them in the freezer. And you can alloquot them into syringes or or however you want to store, store them. Cross crossing species is OK, so I guess I grew up in, in, in, in cat retrovirus days when FELV and FIV were, were, were pretty common.
And so I'm always nervous about using kind of donated cats on a cat. So using dog on a cat or horse on a dog or cat is absolutely fine. And we use loads of the stuff in our our practise, so actually we've started using frozen plasma from the pet blood bank.
I think one good question is, is serum or plasma, is one or other better? So there have been studies that have found there's basically no difference between the two. And then there is the question of storage.
So I said alloquating or, or, or, or, or dividing into smaller portions, so we divide our, our frozen plasma into into small portions that we can use on a case by case basis. And there's, there's evidence with serum that there was one study storing between -20 or -80 that you can get sort of 180 days, is OK. You still maintain anti-lagenase, effects, there, so sort of 6 months at -20 is absolutely fine.
Another study looking at plasma found longer, so 14 months in a dog and 31 months in a cat, but that was at -80, and, and so in a normal practise situation, we haven't got that situation. So I tend to stick with the 6 months in a, in a normal freezer and I'm quite happy with that. And once it's for, that, that my, my big concern is how, how do we maintain sterility, you know, serum is like, it's like an agar plate really, isn't it?
So, so, you, you, you know, at what point does it become dangerous because you're just putting bacteria into the eye. So there was a study, recently looking at. Just that, and for two weeks after falling you're OK.
If you store it in the fridge, take it out of the fridge, put it in, but you use it and then put it back in the fridge. But just to be on the safe side, I, I tend to keep it for 5 to 7 days. I, we, we give, we give generally give people 2 bottles of serum, we give one to use and one to have in the freezer when it runs out.
But it's serum's hard work, you know, if you, if you're not like us and you're not treating eyes all the time, you know, the dog needing serum comes in at 5 o'clock on a Friday and you just want to go home and you don't want to find a donor dog because it's a pub that won't stay still and you're worried you're gonna rupture the eye, and, you know, there's gotta be easier ways round it. And, and the question has to be asked, is there anything better? So, a a a a a commonly talked about thing is EDTA, and again, it inhibits MMPs.
It's got other use eye uses, so, it's a fairly high concentrations, it's been described to in er as a tool in preventing calcium deposition in corneal degeneration. It gets used as a, a preservative, but it does require preparation, you still need to sort of, sort of do a bit of home home pharmacy in your prep room to get, to get this organised. There have been studies, on its efficacy.
So in one, recent study, it was found that greater than or equal to 0.3% is an effective anti-coaginase, and, and in an earlier series of papers found that, 0.2% was sufficient.
0.3% in the first paper was the lowest concentration in the paper. And as a guide, if you make, if you put some liquid in an EDTA tube, so we mix our ETTA drops up with with like a hyaluronate lubricant, you're gonna get a 1.15% solution.
So what, what you can do is fill up one tube to get the ETTA from there and then pour it into, into another tube and you'll get a 0.3% solution. But you know, it requires effort.
And, and then there's an acetylcysteine, which I guess with the, the advent of strames it it it's become much more a product that that's sort of come under the spotlight again and it inhibits MMPs but it's, it's interesting, it's interesting stuff, it has lots of other effects, so it, it, it is a direct antioxidant, which, which, you know, antioxidants are good, as a general rule. It, it's mucolytic, it breaks down disulfide bonds in, in glycoproteins, so it has a use in, in, as a bronchi eucalytic. It affects biofilms, so there are like ear preps nowadays and the, the, that, that affect the, the, the, they're efficacious because they break down the biofilm in ears, and it's thought of as a, it's thought to have anti-inflammatory effects and actually direct effects on corneal healing are talked about, .
That it's generally thought that it has a positive effect on corneal healing in its own right in in in some of the human literature and experimental literature. So it acts by calcium and zinc zinc chelation and it it it also acts by breaking down these dissulfide bonds and it also probably inhibits MMP9 production by corneal cells. So there's been a, there's been an NAC preparation I knew about for a long time.
It's, it's, it's a 5% solution. It's very, very expensive, which puts a lot of people off, and it's also irritant, you know, above 5% NAC is, is irritant. Now strome is a 2.5% solution, so it's below that irritant, it's below that sort of irritant threshold.
And then in the paper that we've, we've actually looked at a couple of times with the other, other things that are available, they found that, actually as long as it's above 0.5% concentration, it's, it's efficacious as an anti-allagenase. So that's based on in vitro studies.
So strames is in that sweet, is in that sweet spot. It's not irritant, but it's efficacious, so, so it's, it's, it's got everything to go for it. It's been around for, for, for, a long time on the, on the continent, and, and, I think it's, it's, it's used, it's used regularly as an anti coaginase successfully over there.
In in humans, NEC is also reported to be useful in the treatment of dry eye. So there are studies, in humans, it's a lot easier to talk to people about how they're feeling about their dry eye and get subjective measurements of how the eye is feeling, and certainly NEC is reported to improve subjective measurements of of dry eye. But objective measurements are, are, are, are less certain, but subjectively, it might help try on humans, and obviously it's muccalytic, so, you know, having a gummed up eye is, annoying.
So if you have got something that that does break down mucus, then that can only be of benefit. I mean that to use it for that would be an off off licence use, but it's worth thinking about. And then in humans, er it because it's an antioxidant and antioxidants are, are kind of, sometimes thought of as the cure for everything, aren't they, but it's reported to help a number of other or have potential for helping a number of other eye conditions in humans.
The other anti-alaginase that that regularly gets talked about are tetracyclines. So, the thing with tetracyclines for me is, is they are antibiotics and it's this whole antibiotic stewardship thing that is, is, is I guess a bit of my stumbling block. So if you've got an option for cycline or a la I should say lor tetracycline or doxycycline sensitive, bacteria in an eye, then entirely appropriate, but.
I don't know how I feel about sort of using an antibiotic for its sort of other effects, but they work by calcium chelation and, and, you know, doxycycline may have other effects, immunomodulatory effects. There was one study recently that where they looked at the concentration of doxycycline in tear films after sort of systemic administration. And actually if you give a fairly standard dose of 5 milligrammes per kilogramme twice a day, then you get a very, very low concentration.
I can't, I'm 0.0000219, I think it was in the paper. So that's a very low concentration.
And, and then the, the paper that we've been looking at as we've been going along where they've been comparing different, anti-laidases, the efficacy of them, they found that you need to have 0.5% or more to be an effective, MMP inhibitor. And so, potentially offercycline is, is a 1% solution, it's 10 megs per gramme, which is 1%, and so.
That is in, in the anti colagena sort of concentration, concentration zone. It is an ointment and I think if you speak to 100 different ophthalmologists, you'll get 100 different answers about, using ointments in ulcerated eyes, but it's there. So which is, which is best?
Is it best to use serum, is it best to use NAC, is it best to use EDTA? I think most of the information on that is based quite rightly on in vitro experiments, so that's kind of putting some collagen in with some colagenase and then adding, adding, adding the various treatments and seeing which one prevents the collagen being broken down. Right, and when you're comparing, you have also got to remember that serum, might have other effects, serum and plasma might have other effects rather than just being a pure, a pure, MM, anti-lainase.
And, and it's really hard, to, to sort of, do experiments to work out. Kind of the importance of some of those things. I think experimental models for corneal ulceration, perhaps not what the sort of thing you really want to be doing, and, and, and whether they actually kind of truly reflect what's going on in the disease process as a sort of subject for debate.
But there's been sort of 22 kind of big looks at which is best. There's quite an old paper now on the, on proteinases in, in the Corne and preocator film, and in that paper, there was no real preference. It was noted that serum also inhibits serum proteases, but they didn't give a preference to, to what was best.
A more recent paper has compared tetracycline, EDTA, NEC and serum, and, all, all three of the, of the things other than serum, the tetracycline ETTA and NAC were better than serum at, preventing collagen breakdown. But there are, the, the, I, I've just sort of noted that the tetracycline is an antibiotic. The EDCCA still does need preparation.
The great thing about NEC, it's off the shelf, it's there, you can, you can have it and it's ready and off you, off you go. The other, the other thing that gets er talked about is should you use combinations, you know, should I be putting serum in in collecting serum into EDTA creating it like an EDTA plasma. And that's, that study, the recent study by Kimmi and Friends, found that actually using combinations didn't really give you any advantage over using the products individually.
So, so, just, just using a single anti-coaginase should be, should be more than enough. There are other things besides antibiotics and anticolaginator to think about, so, ulcers are painful, so remember to give pain relief. No non-steroidals are fine, but like I said earlier on, don't, don't get thinking that a topical non-steroidal is a, a suitable way of sort of controlling that inflammation and, and controlling pain.
The other thing is to think about cyclopplegics, you know, I mentioned the meiosis and that in its own right can become painful, so, so perhaps applying some atropine to relieve that might be useful. But atropine does have other effects. It, for example, reduces tear production, which might be unhelpful.
So, we use cyclopentylate because there was a paper in in normal dogs that is that that showed that it didn't have a a a an effect on the Sherman tear test. And we also lubricate any any ulcerated eye or any eye that we're concerned about ulceration happening in. And my favourite lubricant is sodium hyaluronate, it's mucinomimetic, and it might help.
Corneal epithelial cell migration, it, it, it behaves in a non Newtonian fashion, so that's a bit like having ketchup, you know, to get ketchup to flow, you need to shake, shake the bottle. And then, and then when you're not shaking it, it doesn't flow, and it's a bit like that, on the, hyaluronic's a bit like that on the surface of an eye. When, when the corneas, when the, lids aren't blinking over the cornea, it stays put, and then when the, when there's a blink, it flows and lubricates.
And then there's, there's a cross-linked, product on the market as, as, as well, that, is reported, to increase some of these beneficial effects. So just quickly just mention some of the surgical options and some of the surgical considerations ever so quickly. Firstly, when should we do surgery?
The 1st, 1st thing is, is, is basically whenever you've got a a 50% or more is our sort of cut-off point for going to surgery, and that can be in very, very young dogs. I think the first, this was an example, I think this little dog was 8 weeks old and he came in with his desmatoseal and, and, and we, and we had to do surgery. I think the first thing to say is, is third eyelid flaps.
I haven't got a photo cos we rarely use them. They just cover the eye up, but they probably don't help beyond being out of sight, out of mind. So, people talk about conjunctival grafts.
I think a small conjunctival graft over a small focal ulcer is entirely right. I think showing a big sort of lump of conjunctival stake over the eye, I'm not so keen on because sure you might, you might sort of help, help the ulcer, but you're not gonna be helping vision going on. So we tend to use a finger er a corn sliding corneal grafter, a CCT where we move cornea from adjacent to the ulcer.
Over over where the ulcer was to, to, provide tectonic support, and then the sort of associated conjunctiva and limbus all shifts down in a sliding fashion to cover where we've harvested the graft from. And you can get some lovely results. So here's a, here's a shih Tzu that had a CCT 18 months previous, and you can just see the conjunctiva and the limbus there, but a really good result.
And here's the Pekinese that we looked at earlier on with the high femur, the ruptured eye, and, you know, it's not the prettiest of eyes. You can still see, you can still see the, the outline of the graft and the the stitch scars, but you can also see the pupils, so we can see in, the dog can see out. There's, there's a brachycephalic, so we've got pigmentation of the transposed cornea, and we've got pigmentation where the nasal folds, are rubbing.
The, the owner wouldn't have the nasal folds excised unfortunately. There's a whole load of other corneal procedures. There's corneal transplants, there's partial thickness, full thickness corneal transplants, there's amnium, there's various bits of intestine and bladder that are reported for for repairing corneal, but the two, the two that we go to as routine are the CCT and the corn graft.
And then finally I briefly mentioned er cross linking. It it it's, it's the sort of new kid on the, on the corneal melting block if you like. So the, the example that I showed you earlier on, that would have been a great er cross linking candidate.
And with corneal cross linking, what we do is we supersaturate the cornea riboflavin, and that basically photo photosensitizes the cornea. And then we shine ultraviolet light at the right wavelength and and the right intensity at the cornea having done that, and that causes the collagen molecules to cross link and and strengthens the cornea. If you, if you do your protocols right, it also sterilises the cornea as well.
And so it it's quite useful if you're thinking there's bacteria there and you wanna try and do something to, to, to lower the burden of bacteria, then cross-linking might be useful as well. And it's, we, we, it's, it's kind of, it's a pretty non-invasive thing to do, so, so we sometimes do it on it on its own, but we monitor closely afterwards, and we often do it, as part of a surgical procedure. So, I've just got one quick, kind of case example of doing, doing that.
There is evidence for it, so, so in the study I've already mentioned this study, where medical and medical in association with cross linking was compared, and the, the medical group, 9 out of 30 in the medical group needed rescue, but interestingly, the rescue, treatment that they used was cross linking, so 7 out of those. kind of did OK once they, they moved up the, up, up the pecking order and had a bit of cross-linking as well. So, there, there is evidence there, although perhaps, low, not, not the highest level of evidence that the corneal cross-linking is a good thing to be thinking about.
So here's, here's just an example using cross linking. Again, we've looked at this case already. It was a, it's a whippet, had had an ulcer for no apparent reason, assumed that it was a trauma, everyone was kind of kind of happy to monitor this also, and, and then it came to us two days later with, with this, this horrendous, horrendous.
Just melt. And so we cross, cross link this cornea. You know, you have to be, there are things you have to be careful of in, in cross-linking such a, such a thin cornea.
But immediately after cross-linking, I think you can see that that it certainly changed the structure of that cornea and, and, and it made us feel much more able to be able to sort of then move on and, and do other stuff with that cornea. So it's not the same dog, but there's a video there of, of Corneal cross-linking in, in process. You don't, you, you, there are various protocols of flashing for 1 2nd on 1 2nd off and all this sort of, all, all this sort of thing, but it's certainly a, a, a, a, a modality that's shown great promise.
We then with that dog went on and did quite a complicated corneal. Grafting procedure and we were able to get, you can see the pupil at the end of the surgery. So as I say, if we can see in, they can see out.
There's, there's still quite quite a lot of management to do with that case to, to maintain corneal clarity, but at least we were able to save the eye. But maybe if that dog had had cytology early on, we might have isolate, we might have seen rods, we might have had the heads up that Pseudomonas was there, and perhaps if we'd started some antilagenase or or if that dog had had the benefit of some anticoaginase earlier on, perhaps some strays or or or what whatever it is, then maybe it would have been a a different, a different story. So, I think that's a whistle stop tour of, keratin Malaysia melting ulcers.
So if there's any questions, and you've got time, I'm more than happy, try my best to answer them or, or feel free to email us, and, either me myself or one of the team will always answer any questions if you use the eyes at Ravetgroup.com email address and we'll get back to you. Thank you.
Thank you so much, David. That was a really good jam-packed session. I found it really interesting and informative, and I'm sure everyone else did as well.
I've got quite a few questions, in the Q&A box, so should we start from the top and just go, I think we might have answered a couple as we went along, just question the chance. So we've got, do you flush with saline after applying for, fluoresine drops. Yeah, I do, do tend to, it, it's quite useful because sometimes you can have like a dent in the cornea where an ulcer's healed and you can think that there's an ulcer there.
And, and actually it's just pooling in the cornea, so it's, it's, yeah, it's good practise to, to, to flush, it's, it's not a must do thing, but it's certainly good practise to. Brill, and then another one here that I do think we touched on, towards the end is how do you control corneal ulcer pain? It, it can be difficult, so, so trying to get the ulcer to heal, so I think this is often where sort of the lubricating and all those sort of softer treatments come in, but we, we kind of go up.
So we tend to use a non-steroidal but if that's not sufficient, then we might use an opiate of, of some sort and sort of go up, go up the ladder. You need to, what you mustn't do is put local anaesthetic in and use local anaesthetic therapeutically, because that's kind of used therapeutically, it's really. Toxic to the corneal epithelium and you can really slow down healing.
So it's useful for examination purposes, but not, not treatment. But, yeah, we kind of, we start with non-steroidals and then, and then work upwards. But it can be difficult.
It's, you have to get the ulcer better really, before the pain goes away. Yeah, and the next one, when do you decide to do a bear chariotomy? A, a bear, sorry, what was, what sort of caratotomy was that?
So, we, well we only do keraotomies if, if we think that there's a scared, if we think that there's an issue, with, with the adherence of the epithelium. I think, I, so, we don't ever do it if there's stromal involvement, so there's only really one situation where we do any sort of keraotomy, procedure. I think, I think that answers the question, I'm not sure.
No, I wasn't too sure either. I was hoping it would make more sense to you than it had to be. Next one is, do you use phenol for SCCEDs, do they melt after that?
I have used phenol. I don't tend to cos I think it's not very pleasant stuff. I mean, I think a lot of practises have a little bit in a cupboard, and I think if, if you use, it's, it, it's certainly an effective treatment for scads, but you need to use it carefully, you know, the, the, the, if you look at the way a cornea changes after you put phenyl on, then it would worry me that that a melt would still be possible.
But, so, so I don't because I tend to use a grid. I have, we have got some but we very, very rarely use it nowadays. Brill.
And then next up, we've got with SCCDs, have you any concerns about the prophylactic aggressive medical treatment delaying or affecting the healing? Yeah, I think I mean you need to be careful because the, the, the, a lot of eye drops have . Preservatives in, so, so unless you're using a preservative free drop and that, you know, there can come a point where you're putting so many chemicals in the eye that you're then, it's then toxic to the corneal epithelium.
So I think every time you use an eye drop, you need to have a cost benefit like is this helping or is this hindering. I think that's, that's kind of one of the great things about sort of maybe using a licenced product is, is, yeah, streaming it's got some preservative in, but, but we know that. It's got through the licence if you use it 4 times a day, then, then it should, then it should be helpful.
But you know, and, and, but, but once the ulcer's healed, then there's no mileage of putting any more in cos that might be counterproductive. So, so yeah, too many eye drops can, can be a problem and you know, in some situations then actually the thing that needs to happen for the ulcer to heal. Is, is we just, you just, the eye, the eye drops need to be calmed down and and less needs to be going into the eye, so there you can fall into the trap that you do too much.
The next question is, does tetracane affect a culture or flourishing? I believe, I believe not, and I would, I would hate to do. Kind of in, I'm, I'm in a, in a, I'd hate to take a swab without putting any local local in.
So, so I kind of think that's the sort of thing that you have to, have to live with, and if, if, if, I wouldn't worry if we ended up sampling after putting fluorozine in. I don't, I don't know, I'm not a microbiologist, but in, in the real world you still seem to manage to culture stuff if they've gone in, and I, I don't think it would be appropriate to do it, particularly in a fragile eye where you're just gently trying to touch the edge of an ulcer. It would be appropriate otherwise really.
OK. This, how do you sterilise the dropper bottles? So we're, we're lucky enough to have, ethylene oxide, so we put them, we put them through ethylene oxide, sterilisers.
I think if it, if it was a concern, then, you want, you could, for example, use, use like a one mil syringe syringe and create little aliquats and freeze those and that's, that's, there's been studies to show that that doesn't affect efficacy. So. Yeah, if you, if it was something that was worrying then you could, there's there's alternatives, it's just what we use.
OK, and then we've got will fluorescent stain worsen the ulcer if applied to a melting corneal ulcer. I think it's a bit, it's a bit, I mean flu flu fluorozine is epitheliooxic, so, so, so keeping on and on putting fluorozine in isn't, isn't a good plan. Once you know it's fluorozine positive, there's no point in proving it again until you reexamine or, or, you know, it doesn't need to go in several times a day.
But I think usually if you've got a severe melting ulcer, then a bit of fluorozine is gonna be the least of its worries. Mhm. And then do you just add saline to the EDTA tubes to make the drops?
Yeah, that's, that's, you certainly can do. We, we actually use a hyaluronate lubricant to make ours up with. I mean, it's, it's, it's kind of where the art meets the science.
There's no, it's kind of what works for you, but, but, but we make it up in a, in a, in, in, in a hyaluronate lubricant. Well. I'm just aware of time and kind of we're still in everyone's lunch hour, haven't we?
So I've still got quite a few questions on here, and they keep coming. So we'll put these all together in an email, bob them across to you, David, and then get them answered and, and sent out to everyone. I was hoping I might get through, but as I was going, there was more and more coming.
So, but no, thank you so much. No, it's a good thing. Thank you very much.
And we will, yeah, speak to you soon. Well thank you everyone for joining. All right, thank you.

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