Hello, Anthony Chadwick from the webinar vets, welcoming you to another one of our live webinars during VC 2021. If you haven't already, please do start doing some social media hashtagVC2021 with some pictures so we can see what people are up to. We're very fortunate today to have David Maggs, who's going to be presenting on a practical approach to diagnosing and treating feline herpes and really .

Close to my heart, ophthalmology, I used to work very closely with Pip Boydell, who sadly left us a couple of years ago, and David and Ron Offre have been very supportive each year of us doing something on ophthalmology at the virtual congress, so, thank you so much for that, David. I, I'm sure David is well known to to everybody on the call, but, for those of you who aren't aware, I will, Look towards the towards the bio. David actually qualified from Melbourne in 1988.

Hard to believe, David, you qualified before me because you look so much younger. He spent 5 years in mixed practise in Australia, England, Scotland, and Wales. I mean, you only miss Northern Ireland out, otherwise you'd have had the full set.

He then completed small animal and equine internships at Colorado State, and then did a, comparative ophthalmology residency at the University of Missouri. He joined the faculty at UC Davis in 2000, and he's one of seven ophthalmologists there. He's also author along with with Ron.

Of Slatter's fundamentals of, veterinary ophthalmology, also Paul Miller, is one of the authors on that. And he's very interested in the ocular surface disease and feline herpes virus. So we've got you on something you're very passionate about in a subject that you're very passionate about, so I'm really looking forward to the presentation, and it's over to you, David.

Oh, well, thank you, Anthony. It's, really lovely to be here. And, thanks again to Webinar vet, putting us, together virtually like this, wonderful.

I'm looking forward to the time when we can, travel and meet each other again, though, in person. So, let's keep hoping for that. But in the meantime, none.

Nothing better than, webinar vets and their virtual conference, which I know they've been doing for many years now. And, and thank you for the lovely introduction, Anthony. It's always a pleasure to, speak at, a programme, and when the ophthalmology section's in memory of, Pip Boydell, and all the, all the better.

So thank you for that. And, and you're right, I love talking about diagnosing and treating feline herpes virus. It's been my career-long passion.

And, I know that wherever you're all, you know, attending from around the world, this is a disease you see. And I, I think that's one of the things that makes it a popular topic, is that it's, a disease that I know you see. If you see cats, you see this disease.

And, and that's sort of my first tip on diagnosing feline herpes virus. The, the way I diagnose feline herpes virus, pretty unashamedly is that I go into the room of a cat with oculus. Surface disease, so a cat with corneal conjunctible disease or some combination of the two, I, I go into that room with the assumption that it could well be herpes virus.

My hypothesis is that it's herpes virus to proven otherwise. Now, notice that that's a hypothesis that like, hopefully all good scientists, I'm going to test that hypothesis. So I'm not going in there and starting the antiviral drug there and then.

But I'm going into the, into the room with the cat in it differently from the room with the dog in it. When I go in, if I was to ask you all now, I mean, what are some common causes of corneal disease, conjunctable disease of the dog? Hopefully you'd have dry eye, KCS at the top of your list.

Then you might have things like, entropionic troon, trauma, allergic conjunctivitis, pannis. And notice that we've gone a fair way down the list, we've got a huge number of dog ocular surface diseases, and we haven't had an infectious one yet. Now take that list for cats, Pannis, dry eye, entroon, nectroon.

Foreign body allergy. Sure, they can get some of those diseases, but at the top of the list for cats, we should probably have things like feline herpes virus and chlamydia. We should certainly have the assumption that they're infectious still proven otherwise.

Now, this, this changes our approach, right? We go into the dog room with a Sherma tear test strip in our hand and a bottle of steroids or cyclosporin in our back pocket. And we go into the cat, room with herpes virus at the top of our mind, and the thought that a topical steroid would maybe be one of the worst things we could do.

So hopefully, I've got this thought process for you, that you approach the room with a very different diagnostic and therefore therapeutic, challenge. And so with the top of the list being things like chlamydia or herpes virus, I'm often asked, well, well, given the huge diversity of ocular surface disease that those bugs can cause, and particularly that herpes can cause, well, what lab tests should I run to make sure that it's herpes virus? Or to rule in or out chlamydia, or how do I, how do I diagnose that it's herpetic disease?

I mean, here's a A huge variety of diseases, all of which, by the way, have an association with herpes virus, conjunctivitis of a unilateral nature here centrally. In the, upper right here, a young cat with bilateral conjunctivitis, upper respiratory disease. Top left here, a cat with a non-ulcerative, keratitis, stromal keratitis with lots of blood vessels, chronic.

Edoema. Here's a cat with sequesttrum. Not all the sequester are associated with herpes virus, but, but some are.

Here's a cat with ear xenophilic keratiti. This is a raised yellow plaque. We can scrape that, find ear xenopils, of course, surrounded by an ulcerative, process as well.

All associated with, not necessarily 100% caused by, but associated with herpes virus, huge variety of disease. So I'm often asked, what's the best lab test for feline herpesvirus? How do I determine if that's the case?

And I must admit, I feel, when I get asked that question, I feel a bit like this, because there really is no reliable lab test for feline herpes virus. Now, let me be more clear on that. There are some phenomenal PCR tests for detecting the virus.

Don't get me wrong. But the problem is they're so phenomenal at testing the virus. And the virus is so good at shedding in normal animals.

Remember that's it's way of perpetuating itself into the next generation of cats. Normal animal shed. In one study, up to 50% of normal cats had a positive PCR test to feel unhappy.

Now, I can toss a coin and do better than that. Well, I can toss a coin and do about that, right? 50%.

If I make an educated guess, if I walk in there and say, well, let me do better than toss a coin, let me look at the animal. Give you my very best shot that it's herpes virus. And then, let's use response to therapy as their final diagnostic test.

Now, a couple of you're rightly thinking, but wait a minute, I see these young kittens with feeling herpes virus, and they're, you know, as long as I give them some antibiotics and keep them well nourished and well hydrated. They're well again by 10 days. So, you know, you can't claim response to therapy as a diagnostic test there.

And you're absolutely right. They're not the cases that I'm gonna claim. And remember, as an ophthalmologist, I tend not to see those.

They're the ones that you are handling so well in your general practises all around the world. I'm talking more about those ones that are coming to you as adults with chronic, grumbling, recurrent eye disease. Now, all the stuff I'm gonna tell you will work just as well for the young kittens as well.

But what I'm talking about when you've got these really tough cases that you're not sure what's causing them, the owner's at the end of their rope, the cat's having recurrent, maybe chronic disease. They're the ones that we can use response to therapy as our final diagnostic test. And the owners love it.

The owners love it. Because you say to them, it's just my opinion. It's one bloke's opinion, as I like to tell them in Australia.

It's one bloke's opinion. But my opinion is it's better that I don't, I don't spend your $150 US dollars on that PCR test. And at the end of it still have to sell you the therapy, and oh by the way, the test has a 50% chance of being positive in a normal cat.

It's better to say, let me have a really good look at your cat, let me have an educated guess, and then can, can I, can I get you, you buy in on on the therapy? We'll have to spend the very, have to spend money on the very best therapy. And you're gonna need to give it really.

You're gonna have to be very compliant, you're gonna have to give it just how I tell you to give it. If we do that, there are now such good therapies for filling herpes virus. In the form of hamcyclovir, and I'm gonna talk to you about others as well, but I want to promote pamcyclovir as a diagnostic test, yes.

And such good therapies for chlamydia in the form of doxycycline, that it's my position, it's my one bloke's opinion, that if the cat doesn't get better, On one of those therapies, then it's not the disease that those therapies are appropriate for. I'll explain that some more in a minute. But that's why I'm saying to the owners, Can I get you buy in, we're not gonna spend the money on the test.

We're gonna spend the money on the very best therapy there is. And if I'm right, you'll get better. And if I'm wrong, we'll use the opposite therapy.

Now, I've got to have also ruled out the fact that there isn't dry eye, that there isn't entropion, that there isn't allergic conjunctivitis. So don't, don't get me wrong, I'm not going in there with an antiviral or doxycycline as my only therapies. I'm going in there looking for non-infectious causes, failing to find them, I'm saying, OK, what's the most likely to work here, and here you go, try this out.

You see how I've approached it almost like a binary situation. Now I'm eliminating the foreign body. I'm looking for the dysychia, I'm doing all those other things that are less common.

But failing to find them, I'm saying it's almost like I've got an old fashioned balance on the counter top, an old fashioned scale. And I got a pocket full of pebbles. I got this pocket full of pebbles, and I'm almost going to make a binary decision as to whether I think it's herpes virus or chlamydia.

And some people say to me, Well, couldn't it be something like mycoplasma as well? And it could. But even as an academician, I don't really care because what's my next test response to therapy.

And doxycycline's the right thing for both the chlamydia or the mycoplas either the chlamydia or the mycoplasma. So you see what I'm doing? I'm going in there after I've ruled out non-infectious causes and saying, well, this is sort of binary.

Are they gonna go home with an antiviral or doxycycline? And all I'm gonna do is put pebbles on the side of feline herpes virus, or pebbles on the side of chlamydia and see which way the balance falls at the end of the eye exam. And here's how I do it.

I know at first, you look at this and go, Well, there's a table full of pluses and minuses. Well, what does all of that mean? Let me highlight a couple of things that I think will help you to work your way through this in the exam room.

The way I tell the students to remember it is that chlamydia causes caucacumosis and herpes causes hyperremia. Now, I get it. You look at this scale, this table, and they both do both.

It's a weighted balance. It's a weighted judgement. That's why the scale's there.

So what I do is I look at the cat and I say, Look at his degree of conjunctivitis. How would I rate the swelling, the edoema, the chemosis? And given his degree of conjunctivitis, how would I rate the hyperemia?

And do you notice that herpes tends to have a more hyperemia dominated, it's not one or the other, it's not binary, or more hyperemia dominated conjunctivitis, and chlamydia tends to have a more. Chemosis dominated conjunctivitis. Now don't get me wrong, none, very few, we'll come to a couple of minute, very few of these are pathonemonic, you, you got the diagnosis, but neither is the PCR assay.

And notice that if we add in one more here, one more conjunctival sign, we can really make a difference. Maybe, we can really make a difference, maybe. Because herpes virus is really good at ulcerating epithelial surfaces.

That's why it causes corneal ulcers, and you're used to looking for corneal ulcers. Drop a fluorocine stain. Watch the, shine a blue light on, look for a fluorescene positive region.

What we're talking about here though is conjunctival ulceration, and it can be found by using exactly the same technique. Drop a fluorocene, but instead of, or I should say as well as examining the corneal surface, examine the conjunctival surface with blue light and look for fluoroine positive areas of conjunctival ulceration. Or look for another sign that confirms conjunctival ulceration, and that is blood haemorrhage from the conjunctival surface, sero sanguinous discharge, that has come from an ulcerated conjunctive.

Now notice that here we've got a difference. This isn't a weighted judgement of 3 + hyperemia to 2 + hyperemia. This is a situation where, to the best of our knowledge, chlamydia and mycoplasma don't cause conjunctial ulceration.

And herpes virus may cause conjunctibal ulceration. So what does this mean? It means you go looking and if you fail to find it, you really don't know what to do.

You can't put a pebble out of your pocket under one side of the scale or the other. But look what happens if you find conjunctival ulceration. You take all the pebbles that you have in your pocket, you put them all on the herpes virus side, and you walk out of the room and decide whether you're going to use antivirals or not.

Because you've already made the diagnosis. See how the plus minus versus the minus means if you find it, you've made the diagnosis. That means look, look, and look again for something like that.

So here's two classic cases, and you can have a look at these and figure them out for yourself there at home. Ate the chemosis, the swelling for both patients. Rate the hyperemia for both patients.

Look for signs of conjunctival ulceration in both patients. Failing to find any conjunctive ulceration, you can't do anything. Finding some, you can make your diagnosis.

So let's do it together, let's start with our patient up here in the top left. I would say that's very marked chemosis, to almost to the point of obscuring the cornea. And strikingly little hyperemia, especially when you compare the two, the degree of chemosis compared to the degree of hyperemia.

So for the chemosis, a pebble on the side of the chlamydia. For the relative lack of hyperemia, a pebble on the side of chlamydia, I'm sorry, a pebble on the side of chlamydia. That's two pebbles.

For the lack of conjunctival ulceration, no way you can put pebbles out, but we're starting to lean towards chemosis. Now let's look at the bottom right, starting to lean towards chlamydia. See, I've convinced myself of the two being parallel.

Now let's look at the slide on the right, the image on the bottom right. Here we have a patient who has really hot red hyparemic conjunctiva, to the point of bleeding here, and a sero sanguinous pink stained discharge down here. We could stop right there, but let's finish it by saying, compared to the hyperemia, the chemosis really isn't that bad.

So for the relative lack of chemosis, a pebble on the side of herpes virus. For the relative intensity of the hyperemia, a pebble on the herpes virus side. And for the conjunctival ulceration, empty your pocket of pebbles onto the herpes virus side and decide whether you're gonna do an antiviral drug or not.

Now here's another one that has plus minus on the herpes side, and absolutely not on the chlamydial mycoplasma side. Again, look for this finding. Finding it, you've made the diagnosis.

So what do I mean by keratitis? Well, keratitis, of course, you know, means corneal inflammation, but that doesn't always mean ulcerative keratitis. We've seen very many non-ulcerative keratiise.

So look for all other signs of, of inflammation in the cornea, blood vessels, edoema. White blood cells, of course, ulceration, malasia. We're looking for signs of inflammationitis, itis of the cornea keratiti.

So, as I am finding it makes all the difference. And if by chance you happen to see some sort of dendritic. Ulcer dendritic teratitis, some form of branching, linear, maybe punctate.

Then you've made the diagnosis. And I want to, I want to, acknowledge Terry Kinvig, who gave me this, slide, this image up in the top left, an absolutely striking, fluoroine positive dendrite in CAT. Now you might say, here's a guy, you know, Mag's a guy who's studied herpes virus all his life and he's using somebody else's photo for this.

And there's a take home from that. This is a very, very rare finding. So don't rely on dendrites as being the only way to diagnose herpes virus, but celebrate them when you find them.

You have just made a strikingly good diagnosis when you find something like that. More likely, you'll see something like the bottom right image here. Some form of star-shaped dendritic linear to branching, in this case, corneal scar.

So look for anything that is of this dendritic branching shape and be pretty convinced in the bottom right and absolutely finish put all the pebbles out on the herpes virus side on the top left. Well, let's do a case together, and you can work this one out. Here's a cat.

This isn't your young cat who comes in with bilateral upper respiratory disease, bilateral conjunctivitis, and, and you know the diagnosis, right? And he's gonna get better by himself and with supportive care anyway. This is the adult cat.

An adult female spayed abyssinian, and she's come to you with a chronic, unrelenting, unilateral plethora alephra spasm and a pira, so. A little bit of mucoid discharge, largely watery discharge, a serious discharge, and just a constant intermittent squinting and obvious pain in that eye. Both the pupils have been pharmacologically dilated.

There was nothing wrong intraocularly. There was nothing wrong at the left eye at all during our exam, and nor did the owner have a history of any concerns about the left eye. Now, as we hone in a little bit here, I was gonna get you to look closely at this.

Think about your little, your assessment of, chlamydia versus herpes virus. We found no other cause, so we, we were backing into it's going to be infectious. And let me just give you a couple of seconds there by yourselves to think, OK, let me rate the chemosis.

Put a pebble on chlamydia or herpes. Let me rate the conjunctival hyperemia pebble on either side. Ulceration, if I can find ulceration, I'm, I'm done and dusted, it's herpes virus, if I can't, I don't know what to do.

Any sign at all of keratiti, corneal blood vessels, corneal edoema, anything at all, and of course we would later stain in this eye, there was no ulcerative lesions on this corneal surface. Of course, dendrites would be our, take home sign. Well, at the end of this, I'm looking at it saying, not very chemotic, pretty intensely hyperemic.

No real absolute areas of ulceration, and none proven by, fluorocine stain on the conjunctiva or the cornea. But the cornea needs our closer attention. And I hope a coup a couple of you will have a chance to look also at the, some of the other ophthalmology seminars.

And my other seminar is in how to do a good eye exam. And one of the things you'll find that I emphasise over and over again in that, 50 minutes is using a bright light and some magnification. And you can see that when we magnify this, that there are, there's a little peripheral band of edoema, so a little by the way, here's the sclera, the white coming down to the corneal scleral limbus, and then the cornea with a big dilated pupil behind it.

Third eyelid here protruded across the eye. And you can see that there's a zone of edoema here, just a light greyish blue, but most importantly, some blood vessels that cross the limbus, extending out a couple of millimetres, perhaps maximally here onto the cornea. You can put all the pebbles on the herpes side and, and go home for the day.

You're done from a diagnostic point of view here. Best of our knowledge, chlamydia doesn't cause keratitis. So it just shows you how the exam can be your friend.

And by the way, that patient, we could have found to be feeling herpes virus positive on our, test. Because it was the cause of his problem. Positive because he happened to have some shedding that day, but it was not the cause of his problem.

We could have found him to be negative because he wasn't shedding at that time. Remember, it can be intermittent. Could have been negative because we didn't sample the right area or it was the, the DNA was lost as in degraded on the way to the lab.

Could have been negative because the lab's sensitivity didn't pick up that DNA. We have all sorts of ways of false positives and false negatives. So the test isn't perfect, neither is guessing, but gosh, it gives, you, a, a head start and gets the owner, right with you, I think, for the next phase of treatment.

And that's what I want to spend the second half of our session today on, which is how do I treat, once I reach that, once I put all the pebbles on the scale. How do I treat feline herpes virus and herpetic diseases. And, here you'll see that my, again, I'm, showing you some dendritic ulcers.

At this time, I want to acknowledge Marc Masce, one of my early, mentors and one of the people who got me really fascinated in feline herpes virus. And I want to also comment and draw your attention to the fact that these are stained, both eyes are stained with rose Bengal stain. Now the, the eye in the top left here is a human eye and the eye in the bottom right here is a feline eye.

But you can see that both are affected similarly and both are stained similarly. So let's talk a little bit more about Rose Bengal stain. Not an essential stain for you to have in your practise, but a number of people ask about it.

And I want to draw your attention to a very similar, actually preferable stain, called liamine green. Liamine green. Actually preferable to rose bengal while doing the same job, because it is less toxic to the corneal surface.

Now, fluoroine, back to our old favourite, fluoroine adheres to collagen. So you need to have degraded or ulcerated, removed. All 67 layers of the corneal epithelium and expose the corneal stroma, or the conjunctiva.

What would happen if you'd exposed, scraped away, lied, virally ruptured 3 of those seven layers? Well that would be a fluorocene negative cornea. That would be a cornea that doesn't retain fluorocine stain.

However, that would be an, a cornea that would retain liamine green, or rose bengal. Rose Bengal, Liamine green, stained dead and dying epithelial cells, sick and dead epithelial cells. Fluorocene requires that all have been, eroded and that you expose collagen.

So it will detect earlier erosions before fall ulceration. That's a bonus from this, image though. These images are here to remind us that when we talk about antiviral therapy for cats with feline herpes virus, we are really lucky that humans get herpetic keratiti conjunctivitis due to a very similar virus.

The reason we're lucky is that I don't know that there would otherwise be any drugs that we would have, any antiviral drugs that we would have useful for us. Turns out that there's not one antiviral drug that was developed for cats, and there's not one antiviral drug that was developed for feline herpes virus. The good news is, there is a large range of drugs that were developed for humans infected with human herpes virus, HSV one, herpes simplex virus one.

However, when we borrow one of those drugs, And use it in a cap. We are taking two giant leaps of faith. We are saying, well, because it was effective against HSV one, it'll be effective against FHV1, right?

No. That's not always and reliably and certainly not predictably true. And we're also taking that giant leap of faith, which veterinarians are way less likely to take, we, we know not to do this, right, where we say, well this drug was safe in a human, it'll be safe in a cat, right?

Clearly that's a very unwise assumption. Now, Let me moderate that a little bit by saying that when you take an eye drop that was developed for a human and apply it to a dog or a cat, it will almost certainly be safe at the ocular level. That is to say, it won't cause corneal ulceration, it won't cause conjunctivitis any more than it will do so in humans.

But we. You do have to worry a little bit about systemic absorption of some of the more systemically toxic drugs. But it's generally safe to say, look, this is safe on a human eye, it'll be safe on a dog or a cat eye.

That's a pretty good. Of course, the oral preparations, the oral antivirals that I'm gonna talk to you about, absolutely not a safe assumption at all. In fact, the, the antiviral drugs as a group are remarkably toxic.

And so you see the subheading on this slide here is that I have a saying that you have to earn an antiviral. And the, the residents that work with me here at UC Davis are, are used to this. They'll come out of the exam room and they've got this diagnostic steps that we've just done.

They've got this down. And they'll come out of the room and they'll say, I'm almost certain this is a feeling herpes virus, and I'm definitely, I realise that response to therapy will be our next step. And then they know to ask or to say, and I think he's earned an antiviral.

In other words, has the patient's disease, or has the owner's concern about the patient's disease, let's remember that both of those are important for us, right? Have they been chronic enough, severe enough, recurrent enough? And each of us will have a different threshold for that.

I can't tell you when they've earned an antiviral. I just want you to just draw a moment and think about it. We, I think, find ourselves, incorrectly, by the way, saying, Well, I'll put him on a topical antibiotic, it can't do any harm.

That's, of course, not true. You are messing, we are messing with the conjunctible flora when we do that. We might be inducing an allergic reaction.

There, there's all sorts of harm we can do, but we're not likely to make the patient terribly sick. That is not always true with an antiviral, I, I mean the oral antivirals. We can't just say, look, we'll put him on an antiviral, it can't do any harm can it it absolutely can.

They have remarkably increased host toxicity relative to say antibiotics. I'm gonna keep drawing comparisons, between antivirals and an antibiotics for two reasons. One is that they're both antimicrobials and so we should think about them in a similar way.

The second reason I'm gonna do it is I think you're just more used to, we're all more used to and more comfortable. Thinking about and using antibiotics, and yet the golden rules that we've learned for antibiotics, we should apply to antivirals as well. So, I'll draw comparisons where I think that they're valuable and I'll show contrasts where I hope that they'll help you as well.

So the first comparison or contrast, I should say, is that, you know, antivirals are a decision that you make a little, with a little bit more consideration for me anyway, than anti, bacterials, antibiotics. And when I say toxicity, yes, of course, oral drugs can have, even some of the drugs I'll show you, fatal toxicity. But even topically, these drugs are, these drugs all mutate DNA.

That's how they work. Herpes virus is a DNA virus. And these drugs, the antiviral drugs are all mutagens.

They all cause the virus DNA, the viral DNA to mutate. The drug companies have come up with some clever ways to make them just a little more likely to mutate the viral DNA than to mutate the host DNA. But it's not binary.

It's not only virus and no host. So you'll see a corneal irritation and conjunctive irritation from these drugs. You'll see a punct date.

disrupted epithelial corneal surface. Something that looks just like the virus, by the way. So we try to limit their length of the duration of therapy and, and the, frequency that we use them.

Having said that, we've got some other concerns. So let's go through, after you've earned an antiviral, what other things do we have to think about? Well, as I said, there's not one that's developed for, and in most countries, not one that's licenced for using the cat.

So that means you're either gonna have to have an extra label use and think about the regulatory bodies in your country, and or you might have to have this drug compounded because it's not available in a suitable formulation for cats or as a topical preparation, for instance. And I'll highlight some of those for you. In gold on this slide, and in gold on all the rest of the slides coming up and now, I'm gonna touch on the most important point on the slide, which is one of the antiviral agents is virus static.

Now let's draw that analogy back to antibacterial drugs. You're used to bacteriostatic, bactericidal, and if you had a disease, dermatitis in a dog that was susceptible to two different antibiotics, equally susceptible. That was, that the two drugs were equal cost, that they were both twice a day, that they had an equal safety profile.

In other words, the drugs were equivalent in every way, but one was bactericidal, one was bacteriostatic. You take the bactericidal every time, right? It's way more likely to be effective, way more likely to be effective rapidly, way less likely to induce resistance.

Dead bugs don't mutate. So, whereas you take the bacteria static one, you're going to have all of the opposite effects of that. More likely to induce re induce resistance, slower to work, need to be given more frequently.

So, we don't have that option. We can't choose a vircidal drug. We have to choose a virostatic antiviral.

There are no vircial antiviral drugs at this stage. So that means a few things. One is we're gonna have to use these drugs topically very frequently.

Let me just put this in perspective for you for a minute. Think about this for a minute. Virostatic means, for as long as I'm present and affecting you as the virus, you just don't replicate quite so well.

Maybe mutate a little bit. Maybe you won't be as strong a mutant as you, as your other wild type would be. But, but when I'm gone, have at it.

Vircidal, should something be available, means I come in, I kill the virus, and I go, and, and that virus doesn't have the chance to recover, to replicate. Let's think about an eye drop. An eye drop lasts on the ocular surface for about 5 minutes, maybe 10.

Let's, let's triple it. Let's say we get a magnificent drop that for some reason lasts on the eye for 15 minutes. And the client says, I can only do night and morning.

You say, OK, here's your antiviral drug, night and morning, 1 drop night and morning. 2 times 15 minutes, 30 minutes for the day, 30 minutes for the day where the antiviral drug is saying to the virus, Don't replicate so well while I'm here, but for the other 23 hours and 30 minutes of today, have at it. I'll be gone.

That's why we shouldn't expect too much of antiviral drugs. That's why we must give them very, very regularly. And we borrow information from the humans, from the human, recommendations, which is every 1 to 3 hours, at least, therefore, 5 times a day.

The other thing is, remember that an anti, that a virus while latent, feline herpes virus while latent in the trigeminal ganglia, is no longer replicating, that's the definition of latency. If it's not replicating, then a virostatic drug will never work. So until we have a vircial drug.

We will never stamp out latency, we'll never cure the animal. We've got to always expect recurrences and the virostatic antiviral drugs we have will control each recurrence. And then remember the induction of resistance thing, particularly if you give them less frequently than you should.

That twice a day therapy is a great way to induce resistance and not produce cure, and certainly not use response to therapy as a diagnostic test. One quick last reminder, none of the antiviral drugs are antibacterial. Let's say you see a cat with a corneal ulcer, you decide that it's appropriate to use an antiviral because you think herpes caused it.

And don't forget that if you would have always, if you would have also used an antibiotic on that ulcer, no matter the cause, then he still needs one. No antiviral drugs are antibacterial. By the way, just like no antibacterial drugs that we use are anti-herpes viral either.

So think about them. So, these 5 or 6 bulleted points here, 4 major bulleted points in the sub bullets. Think about these as at the top of every slide that I'm about to show you next, every image that I'm going to show you next.

Cause I'm now gonna go through a series of antiviral drugs. I'm gonna give you the specifics regarding those drugs, but those points were true of all of them. So that's, think about them at the top here.

Now I realise we've got an audience here from all around the globe, and that antiviral drugs vary quite a bit in their availability and in their cost all around the world. I've tried to put together a little smattering of what I know we can get in Asia, in Europe, in the in the Americas, in the Pacific. But I understand that if you are hoping that every one of these will be available in your area, you may be frustrated.

But I've tried to tailor this for our very international audience. Now Gancyclovir, I put in here too, because it's one of the few topical drugs that is commercially available at the moment. And I'll preface this immediately by saying I have virtually no experience using this drug because up until just recently, it has been frighteningly expensive in, in North America where I'm practising.

It is frighteningly expensive. The nice news though is that it's had widespread use by the European veterinary ophthalmologists and they are claiming excellent results there. The other news that we have is that it has been tested in vitro against feeling herpes virus and it is effective.

There's no doubt that this is a good drug or a bad drug for the virus. It's, it's a a good drug in its antiviral effects. The other thing that's been studied is it's tolerance, it's tolerability in normal animals.

So notice that that Q8 hour recommendation on the slide there is not a recommendation of how often to give it. That's a report of how well it was tolerated when given that frequently in normal eyes. We don't have any published reports yet of this drug's use in fear.

Eyes. However, as I say, the anecdotes coming out of Europe are very promising. If we were to steal the, the recommendations from humans, it would be, well, one drop at least every 3 hours.

You've got to keep this virostatic drug exposed to the virus. You've got to keep the two of them, meeting each other on a very regular basis. So one drop every 3 hours, if you think about that as waking hours, that's only barely 5 times a day.

So let's aim for at least 5 times a day if we're gonna use this drug. Now you see the gold on this one, Cydohovia instantly shining up for us was, wait a minute, twice a day? We can give this twice a day?

Is this vircidal? Nope. There's no viricidal drugs available.

This is an antiviral that you could think of, if you like, as a bit like the azithromycin of antiviral drugs. Cytofair gets taken up by cells and forms a tissue reservoir of drug. And that's pretty darn cool.

Because while it's sitting there, the virus gets to enter the cell and immediately the drug is already waiting for it, it hasn't been washed off the surface of the eye. It's not available as a commercial eye drop preparation, but you can see that it can be made up here in artificial tears. You can make up or we have a compounding pharmacist makeup a 0.5% solution.

One drop, both eyes, and twice a day in this study that I'm quoting down the bottom here, of an experimentally inoculated set of cats showed tremendous statistical significance. So we've got one of the premium veterinary studies, you know, double blind masked, double masked, placebo-controlled, prospective trial. Great result.

I've put nasallamo scarring down the bottom here in with a question mark. That's the reason this drug didn't make it to market for human use. We haven't seen that or it hasn't been reported in cats, but if you were to have this drug formulated, as recommended, then this is the recommended frequency, and this would be something that would be a possibility that you may want to watch for.

Acyclovir, I know a number of you have access to this in your area of the woods, and I want to acknowledge David Williams from the UK who showed us that this drug, when given 5 times daily, but not when given 3 times daily, was highly effective at reducing the clinical signs of cats with Phil and herpes virus. I want to make a really important point here though, this has to be an ophthalmic preparation of acyclovir. And not a dermatologic one for like cold sores, human, herpes labialis.

So, ophthalmic acyclovir, if you have that in your neck of the woods at least 5 times daily and expect good results, with that. Now acyclli is also available as an oral drug. And I want to be really clear that I do not recommend that.

The therapeutic window, that is to say, the, the region between how much you have to give to, to, to get, effective blood levels and the safety, that is, the dose at which you start to see some bone marrow suppression is just too narrow. This drug will induce bone marrow suppression in cats. It's reversible, but, it's still not, in my opinion, safe enough to give for its level of efficacy.

Which, by the way, leads us beautifully into Vallecyclovir. Vallecyclovir is the first of two pro-drugs I'm gonna tell you about. A pro-drug is a drug where the animal, or in this case the human, ingests the pro-drug, and the prodrug is metabolised into the active formulation.

So this overcomes the acyclovir barrier to absorption. Acyclovir is really poorly absorbed. The problem is That it overcomes the barrier to absorption and the cat gets really high concentrations of plasma acyclovir, so high that it kills the cat.

So, yes, valet cycloby is dangerous, but really what it's showing us is how dangerous acyclovir is. Cause valet cyclovir is just the method by which we achieve high Acyclovir concentrations. So I put the two together because it, I just want you to really respect and, and I hope not use acyclovir.

Having said that, there's been some time in history where we've used vib because it was the only oral antiviral available to us. More frequently, more, more recently, we have had access to another pro-drug. It's a highly related drug, which made us really nervous when we started to use it in cats.

And I want to acknowledge, Sarah Thomas and Lionel Sibag, whose studies you see, some of whose studies you see quoted down the bottom here. I've had the privilege of working alongside these two people for, now 13 or more years, and, they have done some absolutely stunning work on haylourian cats. And it's an incredibly complex drug because you have to absorb encyclovir and convert it via a liver enzyme into the active drug of pencyclovir.

Now the reason I'm telling you all of that is because you have to know that cats metabolise drugs weirdly, right? They're just, they're just weird at the way they metabolise drugs. Now we're used to that.

But we're not used to metabolism being the activating step. We're used to metabolism being the deactivating step. So therefore we give cats lower doses of the drug.

More spaced out intervals. This is a drug where we have to rely on the liver to activate it, so we have to give him higher doses of the drug at closer intervals than a dog or a human. And that's why I'm recommending after all of Lionel's and Sarah's work, what many of you would recognise as a pretty high dose.

This is the dose that we know will achieve both plasma concentrations and even better. Tear concentrations. This drug, when given at this dose rate, will achieve tier tier pencyclovic concentrations that are effective against feline herpes virus.

Now I'm about to show you why that is so important. Here is tia pencyclovir concentration. Here is the time following the most recent pamcyclovir dose.

You give the cat a pillar of hamcyclovir, we record his tier pencyclovir concentration for the next 12 hours. And this horizontal line is the line above which we want to get it. That's the the dose above which will achieve an antiviral effect.

Notice that after one pill, These, these cats had, a tier concentration level for 4 hours that was effective against the virus. So you give this drug twice a day, that's 8 hours of effective concentration. Remember the, the eye drop?

The eye drop gave us 5 minutes. I allowed it to be 15 for the purposes of the sum. Even if we gave 5 drops a day.

5 drops a day, 15 minutes. We're nowhere near what we get with 2 pills a day, 2 pills a day, 8 hours of effective concentration. And that is whyancyclovir is the bomb for feline herpes virus.

A lot of people say to me, but wait a minute, at 90 milligrammes per kilogramme, I, I don't know how to get that much into a cat, I've got to get it compounded. There are now a couple of studies that suggest that compounding it is extremely unwise, and the reasons for that are it's a very, very bitter, it's very unstable, and at least the pharmacies that have been studied have produced very unreliable quantities. Now I'm not blaming the pharmacists.

It may be that this drug is simply unstable and that's why we're seeing later on an unreliable concentration. Therefore, we're gonna have to find a way of masking that flavour, getting that pill down in a more conventional manner. And please don't use transdermal.

The pharmacists who I call and say, why are you producing a transdermalamcyclovir, say to me, will be because I can give lower doses because it bypasses 1st 1st past hepatic metabolism. Well, that's true for drugs that get get metabolised and degenerated by metabolism. What about a drug that needs activation, then bypassing first class metabolism is a disaster.

That means you have given an even lower dose than had you given it orally. So please no transdermal. And let me finish up by saying, in addition to that hay, in addition to that cytopphobia, whatever you give, always, always, always give some form of topical hyaluronate.

Hyuronate, in various forms here from all around the world, is a mucinomimetic. It mimics the mwin layer, this dark green layer down here of the tear film. The musin layer that hangs and draws the water of the tears back onto the tear film.

Cause back onto the cornea. Remember the cornea is repelling tears, that's its job. That mucin layer is made by conjunctival goblet cells right here.

And those goblet cells get completely ablated, those beautiful magenta goblet cells that should be at this sort of density here, get absolutely ablateded in conjunctivitis. And when you have a low goblet cell density, you have a low mucin concentration of your tears. When you have a low mucin concentration, Your corneal and your conjunctible health deteriorates, so you can see that you get into a vicious cycle here.

And there is now really good growing evidence to suggest that applying a mucinomimetic drug, hyduronate, any form of the the topical hyduronates, not just, we first thought, oh, well, we'll just replace the goblet cell mucin that the goblet cells can no longer make. We thought it was like insulin in a diabetic. Let's just replace it.

It turns out that of course, it breaks the cycle and helps the natural goblet cells to regenerate. And the endogenous production to increase. Couple of other hints.

Please think about stress in these cats with feline herpes virus. I love this website down the bottom. Make a note of this indoor pet, initiative, the indoor pet Initiative out of Ohio State University.

2 a couple of tabs here, notice the tab for veterinarians and the tab for pet owners. Tony Buffington has given a lot of thought to what it is that stresses cats, which is a remarkable thing to think about. And that, that, this is just a tremendous resource for you and your clients.

And please don't put e-collars on cats with feline herpes virus. They're not gonna rupture their own globes by rubbing at it. In fact, there's probably some therapeutic advantage of rubbing.

If you're not seeing enough feline herpes virus in your practise or if it's going away too quickly, you know, if you're able to treat them all and they're not enough of a therapeutic challenge for you, put a few more cats in E. Colis, that'll certainly, draw out the duration and severity of the disease. And it wouldn't be right to finish a talk about herpes virus without talking about lysine.

I know it's become controversial. Here's what I do. I offer it.

I don't promote it, I don't push it. I just offer it to chronic offenders. I have a couple of owners who absolutely swear by it.

I'm not gonna tell them, don't do it. There is some reasonable, peer reviewed evidence to show that it works in some populations. If you are going to give it, they definitely need 500 milligrammes twice daily as a bolus, so a a pill or a powder or a paste or a chew in the morning.

And then 12 hours later, another one. What we found is if they graze it, if they're allowed to, if it's sprinkled on food and they graze throughout the day, then actually we get a, a counterproductive effect. They're actually worse than cats that are not treated with lysine.

And you can give it forever. You know, it's, as far as we know, it's safe. I don't have a preference for the formulation.

Oh, and what about if it is chlamydia, you know, what if the scale, and that wasn't what I was asked to talk about today, they asked, you know, can you talk about herpes virus? But what if the scale tips the other way, and, and you think at the end of the year you think, oh, then that's easy. Doxycycline and hyaluronate, of course.

Doxycycline for chlamydia. It actually cures chlamydia. You will clear the animal, clear the cat of the, chlamydial organism, at 5 to 10 milligrammes per kilogramme, orally, once daily for a week.

And if you treat the in-contact cat, so Ms. Jones has two cats, one of them has chronic chlamydia, treat both, even though neither, even though only one is showing signs. And as long as Mrs.

Jones doesn't reintroduce it, or as long as the cats don't go back outside. Then those cats are cured, lifelong cure, and we don't have that effect for herpes virus. And that's why I say, we now have such good therapies for chlamydia and herpes that we can make the diagnosis.

So, let me finish to recap, Approach the catch from the point of view of let me make a best guess. Let me play the balance and the pebbles game. And if I think it's likely herpes virus, then I'm gonna use hacyclovir at 90 milligrammes per kilogramme twice a day.

Gonna put us on some topical hydraonate as often as the owner can, 24 times a day. And if I see improvement, I'm gonna continue with the hamcyclovir till better. Then a bit more and then stop, do not taper.

You wouldn't taper your cephalosporin, you wouldn't taper your clavulanic acid amoxicillin, so don't taper this antimicrobial either. But continue the high rate long term, maybe forever. If I think it's doxycycline, if I, if I think it's chlamydia, I'm gonna use some doxycycline.

I'm gonna use a topical hydonate. I'm gonna go for 4 weeks and treat all in contact cats, and I'm gonna continue hyaluronic long term. What if they don't improve?

If you get no improvement, then I swap therapies. If 10 days in, they're not improving, I'm swapping therapies. You might ask why don't I give both at once?

Well, I won't have had a response to, I won't have had a diagnostic test. I won't know which one to use next time. And I double or maybe more my chances of side effects, GI irritation, diarrhoea.

So, I just prefer not to do both at once. Anthony, I think we're right on about time to take some questions. I'd be happy to do so, and, and once again, thank you so much for inviting me.

That's absolutely fabulous. Thank you so much, David, and it's fascinating also speaking to you just before we started about your solar roof as well. We're very much interested in sustainability and it's great to see, if you don't have a solar roof in California, you must be an idiot.

Yeah, I mean if you can hear a humming in the background, it's, it's a good day today, we're making power. Yeah, I had a, and a battery in there as well to store, so, fantastic. It's really, really good, and what a great book as well.

This was, the book I was telling you about. Ron very kindly donated, gave me a copy of this when we met in Seville, when we were able to do that strange thing of meeting up together. I've almost forgotten, I've almost forgotten, but it's really been lovely having you on, a great, great talk, really interesting.

It'd be really interesting to hear from those people who are. On the call. What treatment you're actually giving for your herpes cats.

So what treatments out there in the part of the world that you are, and perhaps just tell us where you're listening in from, because it's always interesting to know where, where people are listening in from as well. So, yeah, do put, do put some of that in the chat box. If you've got a particular question, put that in the question and answer, and we can just hear then what what treatments are getting used out there, but .

A really fantastic precis of, of, of that disease, plus of course chlamydia, which again can be a problem. David, as I say, every time you can't hear the tumultuous applause with webinars, it's one of its disadvantages. But Anna said, thank you very much, great lecture, always pleasure.

So she's really enjoyed it. Ira said a great lecture as well. Catherine, praise indeed best webinar ever.

So really, really enjoyed that. Pay is saying thank you so much, wonderfully practical, informative webinar, really enjoyed it. Nanette saying .

She's listening in from the UK. We have been using compounded facyclovir from Summit. To good effect, may try the proper tablets again now.

I can insert a comment on that. I understand that that's particularly at the 90 milligrammes per kilogramme, that's a lot of hams to be trying to push a very large tablet down a a cat's throat, and I know I'm telling you also Dana, don't stress them while you do it. If you, the problem I'm worried about with the compounding is the stability, so what I'd I'd suggest if you really do want to, do need to give it in some other format than a pill, is take the pills, grind them up.

And then make that into a slurry that you can immediately still very bitter, or take those and pop them into a little gel capsule. And that's a tremendous way to tailor the dose to the cat while making it a little bit easier to slip down. It's not that it shouldn't be mixed with water, it's just that it shouldn't stay mixed with water in a bottle and be drawn from the bottle.

It needs to be fresh, freshly done. So perhaps in the net you can let us know how that is compounded cause Summit may be putting it into a little gel capsule, in which case you'd be happier with that, would you, David? Yes, absolutely.

That's in fact the way we do, particularly our really tiny little kittens. And that's often a question I get is what's the youngest age I can do this? And we haven't found the youngest age.

We're just finishing now a study where we've had 400 really just tiny neonatal kittens on hamcyclovirra at 90 milligrammes per kilogramme. So we don't know of a young, too young a cat to receive this. Gareth is saying fantastic, thank you.

He's in Essex, the UK. Lisa, excellent, very enlightening. Sophie, extremely helpful.

Angie's listening in from South Africa, awesome lecture, learned loads. Thank you so much. Anybody's tell, please tell us what you're using, if you're using, you know, which, .

Which antiviral you're using. Hannah's same fantastic webinar as well. Sally's listening in from Switzerland has really clearly explained.

Nicole, greetings from Slovakia. Really practical, awesome talk, thank you. I think there's a, there's a bit of fan mail coming your way here, David.

It would be lovely to see these people in person again. Imagine if we could have a coffee at the exhibit those are the good old days. Well, listen, also, for those of you listening, obviously we've got the Hoover app and I don't know if you've actually downloaded that, David, but if people have specific questions, I think on the Hoover app, you can ask a specific question to David as well because .

So, so that's a possibility. Ninette's saying it's bover, but it comes as a paste, it's not summit. So it's bover that actually makes it.

Elizabeth said, . She's been very personal. She's she's in her 60s, she said, thank you for teaching me so much.

Learning is always rewarding. Liz from Ireland. So that's Liz stay young, it's never too late to stop learning.

60s, that's, that's the new. Yeah, we're, we're all, I think vets are great as, you know, we are lifelong learners. We're, we're fascinated by the subject.

We, I, I think it gives us a kick to stay up to date, doesn't it, David? Definitely, definitely the goal. Now let's see, otherwise, any question, I think you've done such a good job that we actually now really understand herpes and chlamydia and and and we you know, hopefully treat those diseases so much better and, you know, this is one of our aims at Webinar vet is to have the world's most confident vets, because if you go into the consulting room.

With a plan The animal's probably going to get better treatment and of course animal welfare improves, cause, you know, I struggle with my eyes. I have glaucoma and, and you know, eyes can get sore and so I, I also like, I, I don't use the hyaluronate as much as I should, so there you go, there's a tip for me, I'm gonna start using the hyaluronate a bit more. I love it, in fact, we use it with glaucoma drugs in our canine patients as well, it just it mellows out and improves that corneal surface, yes.

I'm a huge hyderonic fan. Yeah, no, I've got it there and I, I, I'm very good on the compliance of the actual medicines, the rimomeidine and, and everything, but . Not so good on, on the how you're on it, so I will make a bigger effort now.

Alright, that webinar's helped you. Yeah, that's been really splendid, David. I have to say I've really, really enjoyed that.