Good evening, everybody, and welcome to tonight's webinar. My name is Bruce Stevenson and I have the honour and privilege of chairing this evening's webinar. I'd like to begin with a huge, big thank you to Photon Therapeutics, for their sponsorship this evening.
And we are very pleased to have their CEO Doctor Mark Leddy, on board with us. Mark is available, for the Q&A session at the end if there are any technical questions that, our very competent speaker does not feel comfortable answering. For those of you that are new to us, we cannot go backwards and forwards through the slides this evening.
So, you know, if there's any questions about, oh, can you go back a slide or two, no, we can't. But don't despair, we are recording the session, and it will be up on the webinar vet's website in the next 24 to 36 hours. And then you can fast forward and rewind and pause and stop and do whatever you want to at your heart's content.
If you do have questions for us this evening, if you move your cursor over the screen, a control bar, normally a little black bar, pops up at the bottom. There's a Q&A box there. Click on that, type your questions in there, and we will hold those over to the end, and we will get through as many of those as what we can.
If we don't get through all of them, we will ask Charlotte. Pretty, pretty pleased, to give us the answers, and we will get the wonderful staff at the webinar there to get those answers to you. So our presenter this evening, Charlotte, graduated from the Royal Veterinary College in London in 2009, and after a year in general small animal practise, she went on to complete two rotating internships.
The first at a private referral practise and the second one at the RVC. Having also undertaken specialist training in the RVC's ophthalmology service, she is now a senior lecturer in veterinary ophthalmology. Charlotte has a wide clinical research interest and enjoys all aspects of veterinary ophthalmology's clinical work.
She's also chair of the RBC's clinical governance Committee, where she oversees all aspects of clinical quality improvement. Charlotte, welcome to the webinar, vet, and it's over to you. Thank you very much, that was a lovely and very generous welcome there, Bruce.
So yeah, tonight, I thought we could er dive into one of my favourite topics actually, which is corneal corneal ulcerative disease. And the reason why this is, one of my favourite topics is because. Actually, I'm a secret surgeon at heart, and this spans a breadth of different surgical, interventions, but also there are some really nice and innovative new treatments out there which can spare, some financial .
Or some finances for our, our clients. So, I've been involved with looking at, a new treatment option, which is, what we're going to get onto a bit later on. So, is there now space within corneal ulcerative disease to move towards some different and more innovative technologies?
So what we're going to cover in this whistle stop tour are a few learning objectives which you'll have on these slides and and you can read at your leisure, and there are some questions as well that you can then test your knowledge on after the, after the webinar, but we kind of want to know what's happening, what those limitations are on the front line, with, in, in first opinion with corneal ulcerative disease, what those. Sort of like inherent limitations are, but also some of our client, considerations too. And with One Health becoming, as it should be, a really, prominent feature within veterinary medicine and the issue of antimicrobial resistance, is there some other things that we can be doing alongside, traditional medications to reduce our antimicrobial usage.
And that's where our photon UVC vet device comes in, to play, and I can happily share with you some, preliminary clinical trial data and some laboratory work that we've been doing with this device. And we can talk about then how, you can practically integrate something like the photon UVC vet into your everyday workflow. And recognise the advantages of treating earlier for some cornereal diseases, especially some of those more complicated ones such as brachycephalic patients.
And then also reducing some of our antimicrobial usage and getting better owner compliance because some of these med medication regimes are really intense for those people and just not possible. And then also we can talk about how we evaluate the current literature. We can talk with a lot along with peers who have experience with different devices and different methods and then how we can implement that within our practise.
So I'm gonna start with some boring things, but I actually love anatomy and physiology because this is the basis of how you can apply your knowledge to something that you might not actually know the name of the diagnosis. So we'll go through some of that now. We'll talk about different types of corneal ulcer, their treatment options, we'll talk about UVC in general, and then also the the the photon device, and then we'll look at the early evidence and some practical applications that we have for the device.
So, my, . Introduction to ophthalmology as an undergraduate was very sparse. I think we had like one visiting lecturer for a couple of hours over the whole course.
And what's nice is that that has changed, quite a lot and my mentor, who brought me along and and trained me during my residency introduced me to this, concept of the colour guide to the cornea, which for me had revolutionised the way, that I thought about, . About corneal disease actually. So, a little bit like catchphrase for those of you, those of you that are, probably millennial beyond and and, was, in Britain at that time, we like to say what we see.
So if you can describe the colour of the things that you're seeing in the cornea. The colour guide to the cornea can really help you to, er whittle down and work out what it is that you are, you know, some differentials and so understanding, The normal anatomy and the normal physiology of the cornea will help you to understand why those colour changes are important and therefore what those things could be. So for example, if we're looking at red or pink.
Then we've got neovascularization and you can see here a list of things that might lead to or contribute to chronic irritation to the cornea, chronic disease processes, along with that comes corneal ulceration which we'll focus on today. And then some other some other things which aren't necessarily on today's topic. White and yellow, so we're looking at deposits and again abscess and cellular infiltrate are a big part of bacteria, in bacterially infected cornelosis.
Then you've got edoema being the blue coloration, and then you've got brown and black thinking about foreign bodies and sequester and things like that. So that's always nice to have in your back pocket and revisit and can help sort of ground you when you're seeing an eye that's multiple coloured, work out where to start really. So, as I promised, it would just be quick, but it's really important that we understand this.
So the cornea is the front part of the eye. I like to think of it as the windscreen of your car, for example, and your eyelids being the windscreen wipers. So in order for you to be able to see out of your car windscreen, then you need the cornea to be clear or the windscreen to be clear.
And it's made up of essentially four layers, so you have the epithelium, so the surface covering the stroma, which is the sort of like chunkiest part or the biggest part. And then you have decimate's membrane, which is a basement membrane of the endothelium. And the endothelium lies a single layer thick on the internal surface of the cornea, which is exposed then to the aqueous humour.
And the reason why the cornea is so special and what we just alluded to with our windscreen analogy is that it's completely clear. It needs to be see through for us to be able to, for light to be able to hit the retina and for us to be able to then interpret an image. And so the reason why it's so special, and so such a specialised tissue is that it doesn't have naturally any blood vessels, there's no pigment there.
The cells that are, sorry, the nerves that are within the corneal stroma itself are non-myelinated, so there's no whiteness, and it's relatively dehydrated. And you can start to think now how this specific point then feeds into your colour guide to the cornea. If you start to have overhydration of that stromal layer.
That relative dehydration is now not, not been achieved and you get blueiness, yeah, water logging of that corne that corneal layer. Again, if you have blood vessels starting to grow into the cornea, you're not going to have corneal clarity and it's gonna fit with some of that pink and red group of diseases there, and the same with pigment. So clinical signs, not only do we have those colour changes that we chatted about, but there are other signs that might lead you to think that there's a problem with the cornea.
So imagine that the, you can't open the eyelids very well and you can't see very well to start picking up some of those colour changes. There might be some other things that the owner's reporting or that you can notice straight away. And so those include epiphora, which is tear staining or overproduction of tears, or discharge, you might get mucopurulent or purulent discharge, for example, squinting, blephrospasm, so discomfort, photophobia, so aversion to light, and then rubbing of the face in general, rubbing of the eyes specifically as well.
And then just focusing again, this talk is just about corneal ulcerative disease really. So you just, I won't go into great amounts of ophthalmic examination. These will be covered expertly, I'm sure elsewhere.
But diagnostic tests that become important for us to diagnose a corneal ulcer give some idea of depth or progression or . Maybe even cause or or being able to describe it better include Shermer tier tests, so. If we have an underlying dry eye disease, then this neovascularization, this chronic irritation, mucopurulent discharge comes into play.
You have low gemat test readings and then you also, can then have, corneal ulcerative disease concurrently. The important thing to remember about Shermer tear tests is that your, your tear reading needs to be taken into context of what's happening with the eye. So a little bit like you're in specific gravity with renal disease, not that I know very much about that anymore, but from when I did know more about it, you have to take it into context of all the other things, you know, how hydrated the patient is, what, you know, renal parameters, you can see on your blood tests.
And so Shermatier test is similar to that. So whilst the normal range reported as 15 to 25, for example. If you have an eye with a deep corneal ulceration and a tear test of 16, whilst that appears to be normal, it's actually probably should be more because a corneal ulcer is painful, giving you a tearing response, and therefore your Schirmer tear test reading should actually be much higher.
So thinking about. Not just the result of your tear reading, but in context to what, how the eye looks, and all these other clinical signs and colour changes that you've been looking for. And then we have fluorescin staining, so we can just do a fluorescin stain, you put a drop of fluorescin onto the cornea, flush it out and look to see if there's any uptake.
That's your sort of final diagnosis of a corneal ulcer, I suppose. And the reason that this works is because the epithelial layer, Doesn't let the fluorescin uptake, doesn't keep the fluorescin on the cornea. The fluorocin binds to the stroma underneath, and so when you have a loss of the epithelium, then you, no matter how much you try to flush away, that fluorescin stain will remain because it has bound to the underlying stroma.
And then you have the sidal test. So before you flush out your fluorocin, what you're looking for is a river of aqueous flowing out of that colour change to the cornea that you're looking at, and this is showing you that the eye is, is perforated. So a positive idal test means you have aqueous flowing out of the eye and that eye is ruptured.
So, before you go ahead and flush that fluorescin out, it's good just to have a look with your blue light to see if you can see, this sort of river of fluid moving. And if you don't, then go ahead and flush it out and and see where you're up to. The other thing that's really helpful in corneal ulcerative disease is cytology samples.
And just like you would, stain your ear cytology, you're not doing anything different or anything fancy, and you're really looking for exactly the same things. So, you take your sample. You, put it onto a slide, you stain it with H&E and then you have a look for all those things.
So you're looking for neutrophils, other white blood cells, any evidence of bacteria, and if there are bacteria, yeasts, fungi, What shape are the bacteria because that will help you to choose appropriate antimicrobials to start your treatment process. And then also you could consider, and something that I do routinely just because of the sorts of cases that I'm seeing are usually very complicated by the time they get to me, we're also doing a lot of culture and sensitivity as well. Once we've documented that there are bacteria on the cytology, then I'll also send that culture off too.
And we can't really talk about . Anatomy and physiology without understanding how the cornea heals, and I'm not going to go into great detail here, I'm going to give you the highlights of the things I wish I'd known as a general practitioner, and this is in order for you to be able to then, give yourself and your er clients realistic expectations. So if you don't understand, the anatomy and the physiology, you don't understand the healing process.
How do you know when to stop medications or when to reduce medications, or actually when medications won't be enough, for example, if you have something that's much deeper. So if we talk very briefly about corneal healing. We're gonna focus on the sort of main layers of the cornea, and so we'll start with the epithelium.
If you have, a very small amount of the surface layer of the epithelium that is lost. And that's the only defect that you have on the cornea, then within 1 to 2 hours, those very superficial cells of the epithelium will start to slide across, will start, start to slide and get bigger and, and move, together in order to try to heal, and close that really sort of superficial, defect. When we're talking about the epithelium again, you have the basal epithelial cells, and these cells start to regenerate from the basement of that epithelium and then replace higher and higher and higher over the levels, and for a complete cycle from the base to the top, takes one week.
And then if we start to think about, OK, if we have a more severe defect that might evoke a vascular response and neovascularization, then. It would be really handy to know how quickly that advances, how long does it take to start to form. And so we know that it takes, a good couple of days for the limbal stem cells to start being activated and for these neovascularization cells to start budding from the limbus, and then the rate at which they progress is about 0.5 millimetre a day.
So if we look at this, a sort of isolated picture here. These are a good 2 to 3 millimetres in length, and the owner said, oh, this just happened yesterday. Then we already know that there was something going on that preceded the acute presentation of this patient because we've already had at least 6 days, if not more like 8, or so.
And then the stroma, so the stroma, which is relatively dehydrated and doesn't have very many cells in at all, you can imagine if you don't have very many cells in that space, those ones that are there are going to take some time to be able to regenerate. And so for the stroma to fill in, once the epithelium has grown over the top, this can take weeks to months. And so, a common complaint, that owners have, When you're happy, you've said, look, it's fluoro and negative, I'm really, I'm really happy.
The owner says, but I can still see, you know, a dip, and then you can really comfortably explain, I'm not expecting that dip to disappear, within the next, you know, few weeks or so because it's going to take time. What I'm happy with is that that epithelium has knitted together and the fluorescence staining is negative today. So I think these things are really helpful in order to for you to be confident in when you want to see that patient back, when to change treatments, but also to give you confidence to explain to owners why you're happy about those things.
Or why you're not happy in case there's deterioration. And then finally we have to mention that that poor little endothelium, that one cell layer thick on the inside of the eye, it doesn't regenerate at all. So we're born with the number of endo corneal endothelial cells we're ever going to have.
And these, you know, die over time as the normal cell death process. And so what happens is, the cells to the left stretch out and get bigger and join one another to maintain. That, watertight seal, and then we get to a point when we're elderly, and this happens in our elderly, dogs and and cats and rabbits, we see that these start to leak and so in geriatric patients you might notice a diffuse corneal edoema and that's because their endothelium, has aged over time and is now slightly leaky and let's water into that stromal stromal layer.
So if we move on to think about types of corneal ulcerative disease, . We're gonna start the most superficial and then we'll work through to perforation, and when we have a very superficial, what we used to call chronic ulcers or boxer ulcers or indolent ulcers, we call these scuds, that's the most current terminology. And this stands for, it's a really, sort of unhelpful name, but, these are, spontaneous chronic corneal epithelial defects.
So it doesn't really tell you much, but we shorten it to SCDs. And this is a very particular type of ulcer, and it's really the only ulcer that should be debrided. This is where we have a hyaline acellular zone here shown as red, that prevents the epithelium from sticking down to the stroma, and that's why we get underrunning of that er fluorescin staining and that we get this chronicity because until you debride and remove that red zone, that epithelium's not going to be able to nip back down onto the stroma.
These are usually uncomplicated. There's very rarely bacteria present if you did cytology. There's no infiltrate, there's very rarely colour change to the cornea apart from some edoema around where the ulcer is.
And so antimicrobial usage for these should be something that is, just going to be to stop secondary bacterial infection, and this is where potentially UVC might come in later, and we'll talk about that again. So then we sort of group corneal ulcerative diseases based on a few different things. So you could have underlying cause such as dry eye or KCS ratoconjunctivitis sica, or you could talk about depth of ulcer.
So you could have a superficial ulcer, a little bit like the sceds where it's only the epithelium that's lost, such as. I don't know, something waking up from a general anaesthetic that we forgot to put lubrication in, might get a drying or exposure ulcer. These heal quickly, are usually very uncomplicated.
And then we can get deeper and deeper and deeper through the layers until we get to decimated membrane where we call this a decimatocele. And this just leaves you then, your endothelial layer really before perforation. Then once that is broken, we have a perforated eye and that's we'll be looking for the sidal test to see if there's any aqueous leakage.
And then we can also classify it based off of the texture of the cornea. So if you have a melting of the cornea, or you might have a foreign body for example, that might be very obvious like in this picture here. And one of the big things and one of the big questions to try and get our head around is we've given our standard recipe of treatment that we might always give to a corneal ulcer, but we need to understand, OK, it's come back and it's not healed as I expected it to.
Now I need to work out why. So there's a whole plethora of questions, and very, very, very rarely would it be actually that I've chosen the wrong antibiotic. So, you need to look for, are there any hairs in contact with the cornea, is there any entropion, any ectropion, disticia, ectopic cilia, reasons, on the eyelids themselves, can the dog blink, to work out why, the cornea's ulcer's not healing.
Is it actually that, you have a scared and you need to debride it? Could it be that you have an immune mediated process going on and you actually need to combine this with something like Optimmune or actually is it that it was just too deep and it needs a surgical intervention? So the treatment options that we have available to us and and we'll go through these now in a little bit of detail.
We have medical management, we have surgical management, we have then two different types of UV light. One is cross linking and then the other one is UVC which is, what we've been, working on and, and I guess why we're here today. So, I don't need to tell you, guys out there, but you can think of however many situations where you've been in and the patient and or the owner are just not compliant.
There's various different scenarios where the dog won't tolerate it or the cat, is an outdoor cat and and just won't tolerate being inside, . You name it, we've had every different scenario, and as you can imagine, if you can't give or the owner, us as the the vets and the owner combined can't give the medication that that patient needs, then the likelihood of a good outcome for saving that eye and that vision. It is going to be much less, and so, one of the things that has become more and more fashionable in recent years and certainly since I started doing my residency is placing what used to be very much an equine device in, into small animal patients.
So, sub palp sub palpebral lavage systems are. a delivery system to be able to give ocular medications, from a distance so you don't have to directly apply it to the eye, and be very sort of close to the, to the teeth of the patient. And so this has been quite helpful.
And it with those delivery devices we've been able to give them supportive treatment, especially if the patient doesn't tolerate it by just having, by just giving the drops. So when we're thinking about what medications we need to do, it's really important that we remember, with medical management, we are supporting the cornea to heal itself. So nothing that we give.
As a medication is going to actually heal the cornea. What you're doing is providing the right environment for the body to heal itself, and that's one of those really frustrating things because we often bombard, eyes, very complicated corneal ulcers with lots of medication. And when it doesn't work, we feel badly, obviously, but also it's then adjusting our own expectations to understand, OK, well, we might actually need to change that because something about the environment that we created wasn't quite right or we've missed, you know, something surgical potentially like an eyelid problem.
So bear in mind, you've had done your full ophthalmic examination, you've got a good idea of the history, of the patient and how it sort of happened. You've also done a cytology, so you can work out, OK, I've got. Cocci on this cytology and I haven't seen any fungi, so I'm gonna be reaching for my, you know, my broad spectrum antimicrobials.
I don't have any rods, so I probably don't need to, reach for my fluoroquinolones at this point. Remembering also that if you have any melting, you will need to be looking at anticollagenases and there's a few things on the market now, and also blood products, so the animal's own blood if that's appropriate, and then thinking about pain relief, so oral non-steroidals if possible, and also you can give atropine or cyclopentolate as a cycloplegic for the ciliary body spasm. So there's a big sort of like.
Argument with oneself when you're treating corneal ulcers, depending on obviously the limitations that you have in the moment, we all go through this, OK, so medical actually is probably gonna give you better corneal clarity because you get less scarring, however, it's a race to get that corneal epithelium healed because you have less tectonic support, because you have less tissue between where the ulcer is and the inside of the eye, right? And we've talked about how we might be able to assist, with medical treatment because that might not have been an option before. If you had an aggressive dog, it might have had to have a surgery, even though it would have done well medically, but now we have these subpalpupal lavage systems and also, there are some pumps as well which can give, continuous delivery of er a little bit like a fluid pump, but it goes er through the subpalpupal lavage system.
And then we have a plethora of different surgical treatments, and this isn't a surgical talk, so I'm just mentioning them really for completeness. But when we elect to do a surgical or we elect surgical management for an ulcer, it's usually because we are missing a real quite a lot of the stroma and we're getting down to decime's membrane. Or we have a decimatocele or and or we have a perforation.
And so, there's various different things that we can do, surgically. So we can use conjunctival grafts, we can use, corneal conjunctival transpositions. We could use a free corneal graft from the fellow eye.
So if you're lucky enough to have a dog or a cat that's got two eyes, you could take, a small section of the superficial cornea from the good eye, and then graft it onto the affected eye. We have a corneal donor bank at the RVC, so, patients that sadly, . Have, been euthanized or, or have come to us, and things, have taken a turn for the worse, then we, we have the option to take, donor grafts, and they, these are usually frozen.
And then we also have synthetic materials, so we have, a cell, which is, pig submucos bladder submucosa, and then we also have, amnion, so. We used to use a product, which I'll tell you about in a second, which was, freeze dried human amnion. And then there are other things in which we can do, so for that endothelial failure that we discussed, we might need to reach for doing a large conjunctival grafts which we call Gunderson flaps.
So talking about that freeze dried amnion, myself and a couple of colleagues did, looked back at some cases that we had done and showed that using amnion, as incorporated into different types of graft, meant that we had really good outcome, especially with melting with fungal diseases and also. With, reduced scarring. So amnion has antifibrotic properties, anti-fungal properties, antibacterial properties.
So it's, really quite a nice, thing to have in your back pocket, especially if you're going to do a surgery. And so the trade-off with surgical management is you get good tectonic support, so the likelihood of the eye perforating becomes much less, but we do get more corneal scarring, and the whole idea is that we want to preserve the visual axis, which is the central cornea right over the pupil where most of the light's going to be coming through for these patients. And the final one just to touch on from a surgical point of view is if, if we really have lost all hope, then we can of course as a final option, salvage procedure, remove the eye.
So, the final group of things, which I think are the most exciting, and have become really popular, really since sort of 2022, crosslinking maybe slightly earlier, became, on the scene, and then more recently, UVC. So Cornell crosslinking is where we use UV light, to stop melt the melting process. So what it does is it .
It er will re align the cross links of the collagen to stop it from to becoming melting and we will fix it more firmly in place. It's also Reported to sterilise any microorganisms, so, that's bacteria, fungi and potentially viruses, and we use it, and it's has been used in the literature as well, but we use it, relatively frequently as an adjunct to either medical and or surgical options for for any species, with corneal ulcerative disease. I've put this here because this is our feeling and we haven't looked back at our data in order to be able to publish a paper or anything but, we have a bit of a question mark over whether anecdotally within our, Sample population, are we actually getting longer term in eyes that have had successively been treated with this, cross linking?
Do we have actually, an immune mediated response long term and that's something that they do experience in people, which I didn't know about until I presented this at a human conference in London and the, the human ophthalmologists all were like, oh yeah, we see that, so. Maybe it's something, maybe it isn't, but just to be on your radar. And so, what we do is we drop riboflavin, which is a photo activator, onto the cornea, and we do it very frequently ahead of when we're then going to, do the crosslinking, and then there is a set protocol with the machine that we have that cross links, and it doesn't take super long, probably between 20 and 30 minutes.
So these patients need to be sedated and or or anaesthetized. And so what we did is we thought, right, well, we'll sort of standardise this and study it within our population and we're just about to submit this, hopefully for publication. So what we did is we took bacterial culture and sensitivity swabs.
Of the ulcer and the conjunctival fornix, right before we did it, about between 0 and 2 hours after, but before we started antibiotics, and then we did it again, between 24 and 36 hours after the crosslinking. And so what we showed was that the bacterial growth score decreased, . In both the cornea and the conjunctival swabs, and that the treatment was deemed successful in half the eyes.
Remember this was an adjunct to either medical or surgical treatment, and failure of treatment was not significantly associated with any of the following factors. So just because you're a brachycephalic didn't mean that your treatment was more likely to fail. Just because you had rods on cytology, again, didn't mean you were more likely to fail if you had pseudomonas or a multi-drug resistant isolate.
And so that was interesting for us and again we use it as one of our, you know, bows to our arrow if you like, or strings to our bow in thinking about how we might manage specific er diseases and then. What we came onto after that was UVC light, and so what we know about that is that it's been shown not to destroy, the sort of host cells, in vitro at 3 daily doses of 15 seconds. It's been shown to be safe and effective to use in mouse pseudomonas model.
And it's also been shown to have a 100% cure rate in bacteria in plate experiments. And its penetration importantly is really shallow. So that's important for two reasons.
One, you know that it's not going to penetrate into the eye and cause damage, which with the crosslinking we're not so sure about at this point, so that limits the number of cases we can use for the cross crosslinking. Because we need more stroma in those, whereas UVC has been shown not to penetrate very deeply, and so you could use it technically in a very deep corneal ulcer, and that would still be safe. However, you need to remember if you have a lot of infiltrate.
Within an infected corneal ulcer, you'll only be, sort of exposing the surface, to the UVC light, and so you just need to think about, OK, if I've done that on one day, do I actually need to, to, to repeat it, and we'll come on to that in a second. And so, what we did, was kindly Photonn gave us a prototype so that we could set this staged in our lab and what we did was we, we chose, a whole bunch of our own grown, . The corneal ulcer isolates, so when we submit our culture and sensitivity to the lab, they keep some, and so we regrew a whole bunch of actual clinical, isolates and did this study on those plus a bank of, purchased isolates as well.
And so what we did is we set up this, we did 3 kill zones, and we did various different times from 1 2nd up to 5 seconds, . And what we showed is that short dura a short duration of sterilisation, we thought basically this is gonna be great because it will show that we can reduce the amount of antibiotics that we need. And the most important thing, or not the the most important thing, but one of the really good things about this is that the patient doesn't need sedation, because we're talking about a few seconds, between 3 and 5 seconds really in any given treatment episode.
And so. This not only is a financial win for everyone, including the owner, but also if you have some of those patients that really just can't be sedated or anaesthetized, this is, really has advantages in that. And we talked about the one health implications .
And how important that is in this current world that we live in. So we use these stored bacteria from past patients. We set it the machine at a fixed distance of 30 millimetres from the plate, and as I said we did from 1 to 5 seconds.
And we actually had a problem where our plates didn't dry super well, . And so we between inoculations, they were a little bit wet and what we actually thought was, you know, maybe this is actually just recreating patient blinking during er during this laboratory experiment. And why that's important is because we had some of these where we didn't get a complete kill rate, which is different to what's published in the literature.
But we think that that's probably because it re-inoculated itself because the Agar was a little bit wet, and that actually might be, we sort of are hypothesising that might be what happens in real life when the patient blinks. So you can sterilise the ulcer surface, but then the patient blinks. And so what we found, and it was so exciting because Pseudomonas or rods, as we know are linked to melting corneal ulcers, which are some of the most severe ulcers to treat, but UVC light is really good at killing Pseudomonas.
It had a 100% kill rate in all time exposures over 1 2nd. So you could do 1 2nd and all the bugs on that plate were, were gone. And it was effective against all bacteria.
Except the strep canis had a 100% cure rate at the 5 seconds, so that needed a longer duration. And yeah, so then what we went on to do after the laboratory study was we, Managed to get a pilot study through ethics approval, which we're just coming to the point where we can, hopefully start to, look at some of that data, and find out how it's been getting on. But we, we've done it to, see if it's tolerated and safe in, in.
Awake dogs and cats, and to use this as, as I said, as an adjunctive treatment for, for bacterial keratiis or infectious keratitis in general, but the study specifically was looking for bacterial keratitis. So it's currently in data collection phase middling towards the end now. And it's multi-center, so across a few different referral hospitals and the earlier it, so we unmasked, so this is a masked trial, we unmasked it at the halfway point because what we needed to demonstrate for ethics was that we had no side effects and that this was tolerated and was safe and we had a whole scoring system for that.
And the early results have shown us that we've got some promising results, especially with these melting ulcers with rods. So how, how do you use it? So this was kindly given to me, by Mark, the CEO of, er, Photon Therapeutics, and, this is just really neat demonstration of, of it, and I couldn't recreate this in in the clinic, so I was like, right, I'm just gonna use yours because it's much more er professional.
So essentially you're aiming for a 30 millimetre, 3 centimetre distance and you have that really nice screen which helps you focus, you know, to see the eye and to focus on where you want to, to deliver that UVC. And again, it's really short, you know, 3 seconds is not long, even in, even in a wake and, you know, a little bit agitated patients, it works well. So the evidence to date is really strong, so there's lots of things out there which I won't go into super detail on for the, you know, for the purposes of this, but anybody that wants the references just let me know and Webinarbet can tell me.
But basically, . It's it's been been used well er in in lots of different situations. So within COVID, the, the medical professions were using it to sterilise surfaces and then they started to sterilise wounds, so skin wounds, and then, .
It then was thought, OK, maybe we could do this on corneas, and we've used mouse models, specifically Pseudomonas inoculated mouse models. Then this group, out of Iowa State, they, have used UVC but a different, a slightly different, . Strength and time exposure, but they had some good results with it.
And we've also shown, not we, but Simon, Dean, who also, is the scientific officer at Phon, he's shown that it's safe, as well. And, yeah, so there's lots of stuff out there. I just wanted to really finish by .
Having a little bit of a, a recap on the practical implications and, and why I think it should be one of the different approaches that we have available to us and and how it can be really helpful in practise. So once you've confirmed that you've got a bacteria, or a fungal, or you have a suspicion that you might have herpes virus, for example, because I forgot to say, but UVC has been shown, to, to kill bacteria, virus and fungi. Once you've got that confirmed, or at least you're strongly suspicious, then, you could use this as an adjunctive to your usual topical treatment, and the reason that that's helpful is because it will help compliance, it will reduce the amount of topical medications you need to give, and you can give it, at least 2 or 3 days, once, 2 or 3 days in a row, .
And then, as you know, I've had mentioned, we've anecdotally seen faster healing times and reduced bacterial load post treatment of our, our corneal ulcers in the clinic and specifically those rod pseudomonas ones. It's quick, it can be repeated and it can be done conscious, and I think these are all really, . Welcome additions to what we've had so far within er the spectrum of things to treat corneal ulcers with.
So, leaving you with a question and hopefully just about on time, could UVC light replace topical antimicrobials for some corneal infections in future and I er very much hope so, would be my answer, especially thinking about. Which we haven't done any work on yet, but thinking about, viral, treatments, things where, we get herpes in cats that recrudesces, you know, this very well could be something that in first opinion becomes, . Becomes really well used.
And so, yeah, that leads me to say thank you very much for listening. Hopefully I was on time and very happy to take some questions. Charlotte, that was absolutely fascinating.
Thank you so much for your time this evening. It really has been a pleasure to listen to you. To Mark Leddy, CEO of Photon Therapeutics, thank you for joining us, Mark, and thank you so much for your generous sponsorship to bring this amazing information to us.
So thank you very much to both of you. Charlotte, I guess, the, the first question to ask is, who and where do we get this? I don't know, maybe I should, refer to Mark for that one.
No, I think you can, you can buy it online, right, Mark? Yeah, yeah, currently it's available online, and, well, we've shipped some devices to the UK, but it's been going around the world. So, yeah, just go to our website and, go from there and we'll have a chat with you and we can certainly sell you a device if you'd like one.
Fantastic. And, I'm presuming that, all the backup and questions and that sort of thing are also online then, Mark? Yeah, there's plenty of FAQs there.
We don't know everything about the technology and we certainly don't know everything about ophthalmology, so we have got some, some really good friendly veterinary ophthalmologists who also help us out, but yes, everything you need to get started with this as a new type of treatment, it's all there and everyone's really welcome to contact us about any individual cases or scenarios. Fantastic, thank you. Charlotte, using this in light of your last question there, how, how brave would one be to go, OK, we have a pseudomonas infection here in this melting ulcer.
I'm just gonna go for UVC with no topical antimicrobials. Would you, would you want to have repeated cytology, or would you not go that far and, and combine the both together? I think that's a really great question, and at the moment I am not confident enough.
I don't have enough data, so I think once we start to get, there's a, there's, I know there's at least another 2 or 3 groups and there's gonna be a cluster of these papers coming out, and I think once we've got that nice smattering of different areas and different locations with that information, then, I think we'll be able to give a much stronger indication. For now, what it looks like for me and where it's been really helpful is that these melting ulcers are often hospitalised with hourly or half-hourly topical antimicrobial treatment. And what I've been able to do is really not give it that frequently and that has just been a game changer, I would say for us clinically.
So I would not completely replace it at this point. I wouldn't feel confident enough that, in between treatments, the bacterial load is still not sitting in the fornixes, for example. But it will stop you having to give half-hourly.
You know, exosin or or ofloxacin, during that patient's stay, and you could get much more into a home regime quicker is how I would see that at this point. Excellent. And how often would you recommend and for what, sort of, how many treatments to be using the, the UVC?
So it's very dependent on the severity of the ulcer at presentation. So bear in mind I only see. Really severe ulcers because I'm working in second opinion practise, right, so I think there's a population that you guys are gonna be seeing that would probably do really well with one treatment, one or two treatments.
We have been using it either as a one-off or every 24 hours for 2 or 3 times. OK. That kind of fits in with what Ruth's asking about.
If you have a, a fairly uncomplicated superficial ulcer, would you consider using the UVC treatment once or twice, kind of just as a, in case, rather than using a, a topical antibiotic? So I think at this point we don't have enough evidence to be able to remove the antibiotic. I think what this will do will shorten your healing time because you're reducing the bacterial load, allowing that corneal, the epithelial sliding to occur faster basically and less complicated.
So I think what you're aiming for at this point is reduced healing time, and reduced volumes of antimicrobials, but I don't think we can replace it yet. OK. Yeah, no.
Yeah, that's, I, I mean, it's it's all new technology and that, and, and, you know, using it as a, well, we don't think there's infection, but just in case, which we know a lot of our colleagues do with antibiotics. And that's not a debate for tonight. But, it, it may well be, well, let's just give one or two treatments, and then you can just sleep a bit better at night.
Yeah, and I think because we know that it's safe, but based off of those studies and based off of what I've seen clinically, and the penetration is, is shallow, you know, it's, it doesn't penetrate into the eye to cause cataracts and other things that one might worry about with other types of UV light, that, you know, if you're going to do that instead of, you know, an entire course of antimicrobials that might not have been needed, then, you know, I think there is probably. A benefit ratio for that. OK.
You, you started off talking about the cross-linking and the, the deeper penetration and that. Again, Ruth says, what is the current evidence base? Would you use cross-linking or UVC in as a preference for, Kerata Malaysia?
Yep, so that is a great question, Ruth. And again it's very, sort of, context dependent. So if I've got a melting ulcer that isn't progressing to the point, so I have melting ulcers that come in and within 1 to 2 hours it's progressed so much that the eye's perforated in front of me in the clinic.
In those cases I'd be reaching for the crosslinking because I'm using the additional benefit of strengthening those cross links and halting the malaysia. If I have something that's melting but I still have a lot of cornea left, I can use traditional anti-coagases alongside the UVC and antimicrobials, so, you know, it, it's, it's a little bit context dependent, depending on what's in front of me, but the cross linking is an advantage when you have a very thin cornea, or, or, or the potential for it to become very thin very quickly and you want to stabilise that cornea before it perforates. UVC is not replacing cross-linking.
There's a rule for both. They're they're in different contexts. Speaking of different context, Rod wants to know the difference between what, we're using here or you're using here and the Americans, different wavelengths, different, how or why, and did that come about?
Yeah, I think it was just two groups of people, developing the tool at the same time and they just had different strengths. I don't know if Mark, you had any better information on that than me. Yeah, I can answer a little bit more.
A lot of it was to do with the availability, so. The, the, the photon UVC device has taken longer to develop because we wanted to have the optimised wavelength, and there were other devices, not medically, not for medical use as such, that were out there, and because some of the work had happened on UVC, I know Melissa Cubay and the group at Iowa wanted to try something, so they found the nearest thing that they could to what could hopefully become a medical device and They they they did the work using, using what they could get essentially at that time. And it was really great.
I mean, from our point of view, we were really happy to see somebody else doing the work and looking into it and and it also exposed some of the weaknesses in, in the tech that had to be improved before you could really make it into a medical device. So yeah, it was good that they did that really. Yeah, yeah.
And of course, we know that UV light for sterilising is not new. I mean, I, I'm from the dark ages when I qualified, and, at night, when we turned our theatre lights off, the UV lights came on automatically, and that was our disinfection, for the theatre, because we didn't have any of the the modern chemicals and, and everything else that we have today. Yeah, absolutely, and they in the NHS certainly in COVID, they were using UVC to sterilise all sorts of things and because it's so fast, and we had very short turnaround times and it's it's effective against viruses, they were sterilising whole isolation units exactly like you describe, people use it to sterilise, .
Like devices or implants, things that they need immediately that that aren't sterile, so as you say, it's not. The concept isn't new, but this device being medical grade, I guess, specifically for cornea, that's the like new part. Yeah, absolutely, and I mean they used to scare the living daylights out of us when they told us about don't look at the theatre when you turn the lights off, you know, so.
Speaking of, of, susceptibility and that, any, any idea why strep canis is, is such a stubborn little bugger? No, I mean, it, it's the absolute bane of our life, certainly geographically around the RVC, it's multi-resistant for us within cornea. We're not, I'm not talking about any other parts of the body because I haven't asked any of the other departments, but.
It's a real tricky customer for us on the cornea within our. Area that we service, and yeah, I don't know is the short answer to that. No idea.
Excellent, excellent. Charlotte, there have been so many comments coming through, thanking you for an amazing webinar and, for sharing everything and your time and your knowledge with us. The, the UVC personally is a, is a, a very exciting thing, I think, moving forward.
However, I have to say my personal favourite of your whole webinar was explaining the colour chart. It's not new, but you explained it so well, so yeah. I just think to myself, what did I want to know, you know, what, how, what, what's most important, like what's gonna be most impactful, what did I want to know when I was standing there and I'm thinking I don't know what I'm looking at, you know, making it as.
As sort of like accessible as possible is important to me. Yeah, and it, it is true, you know, there's if you want to, don't hand them a scalpel, an ophthalmoscope. Yes.
So the, the colour chart is a, is a fantastic way of bringing it to life. So thank you for sharing that. You're so welcome.
Thank you for having me. Mark, thank you for being with us. And once again, a huge thank you to you and, Photon Therapeutics for your generous sponsorship this evening.
We really do appreciate it. To everybody that attended tonight, thank you for your time. I hope you enjoyed it as much as I did.
And, as always, Amelia, my controller in the background, thank you for making everything run so smoothly. From myself, Bruce Stevenson, and everybody else, good night.
