Hello, everyone. My name is Ron Offrey, and I'm a professor of veterinary ophthalmology at the Hebrew University of Jerusalem in Israel. Earlier today, I've realised that I've been talking on the alphabet.

Webinars for over eight years. I've started back in March of 2015. I think I've got over 30 recordings in the archives, but it's always a pleasure to be back and I'm glad to be talking to you today about a practical guide to ocular pharmacology.

And basically, we'll be discussing medical treatment of corneal ulcers and secondary uveitis which you're seeing here. We'll be talking about glaucoma, which you see here, and the treatment of feline herpetic keratoconjunctivitis. Starting things off with the medical treatment of corneal ulcers and as I always tell my students, when you're treating corneal ulcers, you always want to keep in the back of your mind that thickness of the cornea is just 0.5 millimetre, OK?

Not half a centimetre, 0.5 millimetre is. You're seeing here are 500 microns, which sounds slightly better, but really, you don't have too much tissue to spare and therefore, even the most superficial ulcers should be treated promptly and correctly cause, as I've said, you've only got 500 microns to spare.

Now, our treatment of corneal ulcers varies by or differs depending on whether we are looking at a simple ulcer that you are seeing here, rather superficial ulcer and we can tell it's superficial even though it's a two dimensional picture, the surrounding cornea. Looks clear. The interior chamber looks clear.

So a rather simple straightforward ulcer versus a contaminated ulcer that you are seeing here, a much deeper ulcer, the red eye around it, indicating secondary UVI and perhaps most important. The mushy like appearance of the cornea as opposed to this healthy looking cornea, which indicates that it is probably contaminated and we'll be discussing both scenarios today, starting with the treatment of the more simple ulcers. So really simple ulcers as you would suspect, the treatment is rather simple.

You should always begin by trying to determine and treat the primary disease. Ask yourself what caused the ulcer. So if you have a history of trauma such as a cat claw, that's probably a good cause.

Perhaps it's dry eye, perhaps the eye is irritated by entropion. I had 2 weeks ago an ulcer that was caused by entropion repair and the veterinarian, the operating veterinarian left the suture that was rubbing on the cornea. So really perform a comprehensive al exam trying to determine the primary cause, treat the primary cause such as removing that offending suture, correcting the entropion, managing dry eye, etc.

And then you wanna treat the Infection topically, maybe there is infection, maybe you just want to prevent infection and we'd use mixed wide spectrum antibiotics as a first line of defence. It varies in product from country to country, and I know we've got a global audience, so I'm not gonna go into names, but whatever is available in your country is a wide spectrum antibiotic and If you feel that the infection is not resolving or you want to sleep well at night and not worry about it, maybe add fluoroquinolones such as ciprofloxetine, orfrofluoxetine, or moxifloxetine as a second line of defence. People have a tendency to add gentamicin ophthalmic drops, to corneal ulcers.

And that's because they're terrified of Pseudomonas infection and rightly so, if the ulcer is infected by Pseudomonas, it could be devastating. However, we do have to remember that gentamicin is epithel toxic. In fact, it can delay healing of the cornea and therefore, I only use it if it's indicated by the results of culture and sensitivity.

However, Treating the ulcer is not enough. We have to remember that every ulcer causes a secondary uveitis, and that's because of a neuronal feedback loop from the sensory trigeminal nerve in the cornea back to the ciliary body and the ciliary muscle and therefore every ulcer will trigger. Spasms of the sidiary body due to activation of this neuronal feedback loop and these spasms of the sidiary body will result in secondary UVITs which also must be treated.

So how do we treat these secondary UVITs? Well, As you probably know, we do not treat it with corticosteroids, because steroids do inhibit the healing processes in the cornea and they may also potentiate the activity of proteases and collaginases that may be present in the cornea, something we'll be talking about in a few slides. And I do emphasise the point that we do not give topical steroids cause actually in human ophthalmology, they are given.

Quite frequently, we're always startled to hear this, but yes, in humans, they are given cause human ophthalmologists are very worried about corneal scarring and the effect it would have on your visual acuity and visual resolution and therefore they do use steroids in order to minimise the scarring. We worry less about scarring, we worry more about melting and therefore we do not give steroids. Which begs the question, if I can't give steroids, can I give non-steroidal drugs?

And in the past, I used to treat secondary UVIs quite often with topical non-steroidals. However, as I've gotten older, I have used them less and less and I don't have my camera on so you can't see how old I am. But let's just say that I trained in veterinary ophthalmology some 30 years ago.

And with time, as I've said, I've decreased my use of Tolenosades in cases of corneal ulcers. You can see a number of papers showing the devastating effect that topical steroids may have on corneal ulcers, leading to corneal melting. If you're taking a closer look, you will note that all of these papers do refer to human ophthalmology.

We've got fewer reports of the detrimental effects of toylenosades on corneal ulcers in Animal patients, but here, for example, is one paper from Georgia in the United States in which so-called boxer ulcers, more properly known as spontaneous chronic corneal epithelial defectsAS and it compared treatment of eyes with and without NSAIDS and as you can see, the application of Toyanous AIDS delayed the healing. These eyes needed multiple medications and these eyes did experience complications. So, yes, please try to avoid topical NSAs as well as topical corticosteroids.

Which begs the question, can I give systemic anti-inflammatories? And the answer is yes, but they should definitely be given patients with severe secondary UVIis and here you can see an example of a rather super ulcer, it's not contaminated. It's very superficial, yet it caused a severe secondary UVIis as evidenced by the hypopion you're seeing here and this patient should definitely receive systemic non-steroidal or steroids.

However, If there is corneal vascularization, then you definitely wanna avoid the systemic corticosteroids cause these blood vessels are going to bring the systemic corticosteroids to the ulcer and make things worse, as we explained a couple of slides ago. So, In this eye, you can definitely use either non-steroidals or corticosteroids. In this eye, you should avoid the systemic corticosteroids, use only non-steroidals.

I know that sometimes systemic steroids are a must. Maybe the patient is being treated for some other disease such as MUE again, look at the presence or absence of corneal vessels to make a judgmental call on how dangerous it is to give systemic steroids in this patient. However, anti-inflammatory treatment is just one component in the treatment of secondary UVIis in these patients.

The second important component is atropine. And atropinene gets 4 exclamation marks because gosh, I wish I had $10 for every patient that whose ulcer was successfully treated by the referring vet, but they forgot to give atropine and the eye was lost. So why is it important to give the atropine cases of corneal ulcer?

Number one, they are a very effective analgesic drug. As I've said earlier, corneal ulcers trigger uveitis because they cause spasms of the ciliary body and those spasms are very, very painful, just like a muscle spasm anywhere in your body. It's very painful due to the buildup of lactate in the tissue.

And if you give a drop of atropine and you paralyse the spasms of the ciliary body, it brings immediate pain relief to the patient. My patients usually don't come back to me and report to me on the effects of the drugs. However, if you talk to a human who has had a UVIis, they will tell you that atropine is a wonderful analgesic brings immediate pain relief.

However, there is another very important point reason, sorry, to give atropine, and that is my drysis. As I've said, every Uveitis causes spasms of the ciliary body, resulting in meiosis, as you can see in this patient here. However, during the course of uveitis, we also have inflammatory material present in the aqueous tumour.

You saw that here in the shape of this hypopion. So we have platelets here and fibrine and white blood cells. We have adhesive.

Tissue, not tissue, I should say, adhesive substances. Again, if you bring platelets floating in the interior chamber, some of them adhere to the interior lens capsule. I know that most of you are a small animal practitioner, so I apologise for bringing a picture of a horse here, but I like what it illustrates.

You can see in a fully dilated horse that most of the interior lens capsule is dirty. It's dirty because we have inflammatory material sticking to it. Only the small area up here is clear of this inflammatory debris.

And as I've said, this inflammatory material is sticky. So take sticky inflammatory material, combine it with meiosis, meiosis causing lots of contact between the iris and the interior lens capsule and you'll get posterior sinicia adhesion between these two. Iss secondary glaucoma and as I've said earlier, you'd probably lose the eye and therefore we want to dilate the pupil, minimise the contact between the iris and the interior lens capsules such as you're seeing here, thereby decreasing the risk of these adhesions.

How muchantropine do we give? Well, the pupil is wonderful in this regard. We begin with twice daily and adjust to pupil size.

Our aim is to get a fixed dilated pupil such as you're seeing here or here. So if you got a fixed dilated pupil with twice daily, you can go down to once daily. Maybe once every other day.

If twice daily didn't result in fixed dilated pupil, then you should go up to 3 or 4 times daily. I don't think there is much point going above 4, but you definitely should strive for a fixed dilated pupil to prevent this posterior sinicia. However, when giving atropine, please remember its potential side effects.

It can cause colic, especially in horses. I know it sounds funny, but yes, I can kill or sound sad. I can kill a 500 kg horse with just a few drops of atropine due to holic, and we've got other parasympathlytic effects.

It reduces tear production, so you will want to check tear production before starting treatment with atropine. The eye that is ulcerated will usually be tearing, so you may wanna check based on tear production in the unaffected eye. Other signs of parasympathletic toxicity such as such as constipation.

This picture here looks very strange. At first, we have a salivating cat and you may be asking yourself, why is this cat salivating on atropine, cause we just said that it reduces both tear production and saliva production due to the parasympathletic effect. Yes, it does reduce saliva production.

However, you put atropine in the eye, it makes its way. Down the nasolacrimal duct into the oral cavity and atropine is very, very bitter in taste and therefore sensitive cats react with profuse salivation to the bitterness of atropine in their mouth. And when I say profuse, as you can see in this picture, it is very, very scary.

If you're gonna send cat home on atropine, please. Do a demonstration in the clinic, put a drop of atropine in the clinic. The cat will salivate and you tell the owner, you see that?

This is perfectly normal, nothing to worry about, cause if you don't do this demonstration in front of the owners, they'll go home and 3 hours later you'll get a phone call, you're killing my cat with the drugs you give. So please. To do a demonstration.

If you have atropine ointment available in your country, you can definitely use that instead of atropine solution, cause less of it makes its way down to the mouth or tropemide, another parasy pathletic drug, it is weaker and therefore has to be administered more frequently, but it is less bitter. And finally, please remember that atropine is contraindicated in glaucoma cause the malysis will lead to closure of the ridocorneal angle and a spike in IOP As I always tell my students, a way to remember it is atroprine in glaucoma, no diploma, and in fact, they like the sentence so much that they even made COVID masks that we used a few years ago. Another thing that you want to add in the case of non-contaminated ulcers is soft contact lenses, which significantly decrease healing time as you can see in these two page.

That are shown here and they also increase patient comfort because they covered the exposed dendrites, the exposed nerve endings of the trigeminal nerve that I mentioned earlier, so they increased comfort and decrease healing time. If you're looking to buy contact lenses, you can buy veterinary contact lenses, and this is an example of a veterinary contact lens because it has 4 dots in it, these 4 circles, black circles that help the owner monitor the presence of the contact lens. This way the owner can know whether the lens is still in place or whether it fell out.

However, these are rather expensive and In fact, we have studies showing that human contact lenses are retained longer and better than veterinary lenses of similar measurements and thankfully, the dimensions of our cornea are very similar to the dimensions of most canine and feline corneas. So you may use human contact lenses that are significantly cheaper than the veterinary product. And please always remember that the cornea is just 500 microns thick.

You've already lost part of these 500 microns due to the presence of the ulcer. So please, please make the owner put on an Elizabethan collar and. Absolutely no excuses are accepted.

Oh, my dog doesn't ru. He he's OK with it. He can't eat with it.

No excuses accepted. Please protect this cornea. Please protect the little tissue you have remaining.

However, with the standard treatment, some ulcers do not heal. We should say, we usually say that an uncomplicated simple ulcer that is treated properly should heal in 10 to 14 days. If it doesn't heal, that, then I can quote my friend David Max from the University of California, Davis, that says that if it didn't heal in 14 days, don't change treatment, change your diagnosis, meaning you have missed something in the diagnosis of this ulcer and that's why it's not healing.

So therefore, repeat your ophthalmic examination, paying closer attention to the anatomy of the eyelids. Maybe you've missed. A slight entropion or a tropion.

Check again for the sticky traysis, invert the eyelid to look for ectopic cilia on the inner aspect of the eyelid. A foreign body, don't forget that foreign bodies may hide behind the third eyelid or other evidence of trauma. Maybe the dog is not blinking because of.

Cranial nerve 5 or cranial nerve 7 neuropathy, maybe it's unable to blink, maybe it doesn't sense anything touching its cornea and therefore it blinks less. Repeat the Schirmer tear test to check for dry eye. Perhaps it's a boxer ulcer, the scads that I mentioned earlier, or maybe it is a contaminated ulcer which we will be discussing next.

But again, if it doesn't heal, you have missed something, please repeat your off. Examination. Here is a paper out of the United Kingdom looking at assertive corneal diseases in over 100,000 dogs and the breeds in which it is most prevalent.

And take a look at this list, you will see that most dogs affected with Corneal ulcerative disease are the same dogs that have dry eye or the brachycephalic breeds with the ocullo brachycephalic syndrome, such as the pugs and the boxer and the shih-tzus and the bulldogs and the spaniels, etc. Etc. So these are the same breeds that present with anatomical problems or with dry eye disease and therefore that's where the corneal ulcerative disease is more prevalent and this is what you should check for.

So if we suspect that the cornea has become contaminated, then you should consider scraping for cytology and culture. When I went to school, we used to say that culture should be done first, and that's because cytology requires the application of topical anaesthetic and we used to say that the preservatives that are present in the topical anaesthetics will affect the results of culture. However, This has been disproven by a couple of papers that you are seeing here and indeed you can put topical anaesthesia, fluorine, tropeomide in these corneas and still take a diagnostic culture and sensitivity.

And again showing you the two types of ulcers. In this one, I'll not take cultural insensitivity. This one with the nasty looking ulcer of the entire cornea being affected, the mushy appearance of the cornea, I'm definitely gonna take cultural insensitivity as soon as it presents.

I know that some people may be scared by taking a cultural insensitivity swab and trying to collect a sample from this cornea. So you will be glad to know, to read this paper showing you that in fact, you can collect a sample from the conjunctiva and it is just As diagnostic, OK. So you can sample the corneal ulcer directly, you can sample the conjunablehonics and the bacterial isolation will be similar with both techniques and as it says here, please submit both fungal and bacterial cultures.

So we've taken our cultures. Next, we want to collect our cytology sample. As I said, that requires the application of a topical aesthetic and a collection of cytological sample.

Cytological samples may be collected with a to brush with a special spatula or with a blunt distal end of a scalpel blade. Here is a paper from the University of Florida comparing these through three techniques and I like it very much because actually it proved that the Handle and of a scalpel blade actually yielded the samples with the highest cellularity. So instead of investing in the more expensive instruments, just a simple blade handle can be used to scrape the cornea.

However, I caution you if you wanna Collect a diagnostic sample, you do have to scrape and when I say scrape, I mean scrape the cornea vigorously in order to get a cellular sample. Just gliding softly and slowly above the cornea will not Result in a diagnostic sample, you do have to scrape it vigorously, otherwise you will not get a diagnostic sample, but if you did it properly, then you may see the bacteria or the fungal agents in your sample and adjust your treatment accordingly. Unfortunately, many of the contaminating agents in these complex ulcers have protolytic enzymes.

I'm talking about fungal agents like aspergillosis. I'm talking about Pseudomonas and other bacteria which secrete proteases which secrete collaginases that degrade the Corneal stroma. We also have degrading enzymes present in neutrophils, in the tears, in the fibroblasts of the cornea itself and all of these proteolytic enzymes combined together in order to cause what what we call a melting ulcer in which the cornea really degrades in front of our eyes and therefore, when we have A contaminated ulcer and we're presented with a melting cornea, then we really need to prevent the activity of these protolytic agents.

We can do it with collating agents, . Such as EDTA or acetylcystein which bind cofactors required for the enzymatic activity of these degrading enzymes, tetracycline is another substance that will inhibit the activity of these enzymes. And it also has an additional beneficial effect in that it is immunomodulatory.

So we may give topical or systemic tetracycline, and I mentioned systemic cause tetracycline is one of the few antibiotics that is actually secreted in the tear film. However, I am not giving tetracycline for its antibiotic effect, which is rather limited in its efficacy. We are giving it more for it, the anti-proteolytic and immunomodulating effect of the Tetracycline.

However, many studies have shown that the most efficacious substance, anti anti-proteolytic substance would be plasma or serum, and that's because they contain alpha 2 microglobulin. Which bounds, binds to the proteinases and produces very effective inhibition. It also contains growth factors and fibrectine which my teachers back at the University of Florida, called the feel-good factor, once again, increasing patient comfort.

Serum is something that I absolutely love using in contaminated ulcers because it's very safe. There are no contraindications. It is not toxic, therefore, it's impossible to overdose a patient.

When we have a case of a melting cornea, I'd hospitalise the patient and we'd have a technician apply a drop of serum. Every 1 or 2 hours until the melting stops. Obviously, it is cheap and it is readily available.

And an important note, you don't have to use the patient's own serum. As I've said, many of these patients will be a pug or a Pekinese with a deep ulcer and a very painful eye, and you'll struggle to extract maybe. 2 or 3 ccs of blood from which you can produce maybe 1 or 2 ccs of serum, forget it.

Your life will be so much easier if you take serum from another patient with owner's permission, of course, or even another species in our teaching hospital. I collect serum from horses. We Extract the serum, put it in small bottles, store it in a clinic freezer for up to 6 months, and then when the owner comes, you simply pull it out of the freezer, dispense it to the owner, they should keep it refrigerated and very importantly discard after 8 days, even if there is serum left because of a contamination of the samples.

So we've taken our cytological sample and our cultural insensitivity. We have treated the patient with serum and we adjust our medical treatment, as I've said, increase the frequency of serum, adjust the spectrum and frequency of tapol and. Antibiotics based on cultural and sensitivity results and, and systemic antibiotics, especially if the cornea is vascularized.

As I've said earlier, many systemic antibiotics will not reach the cornea because very few of them are secreted in the tin. Another way of delivering antibiotics is through subconjunctive injections. As you're seeing here, you can inject up to 1 millilitre of antibiotics and it's actually a very simple technique.

Put a drop of tohetic, grab the conjunctiva with forceps and just go in with a needle, inject 1 mL and then withdraw the needle as your clump. With the entry point with your hemostat, so it doesn't leak out. Use only formulations that are intended for intramuscular or intravenous formulation.

You're not giving formulations intended for oral dispensation and here you've got the doses of drugs that can safely be given to these patients. But unfortunately, sometimes medical treatment is not enough and you may have to refer these very nasty looking ulcers to a specialist who will perform a conjunctival graft surgery in order to save the eye and prevent perforation. Onto the second disease we want to talk about, which is glaucoma, and the medical treatment of glaucoma.

So when we are treating our patients for glaucoma, you should keep it in the back of your or you should tell the owner that we have two aims. In treating these patients, #1 is to reduce the pain cause obviously this eye is very, very painful. And number 2, we want to prevent further damage to the retina and to the optic nerve, further loss of vision.

However, owners should be aware that previous damage is mostly irreversible and we can only prevent further damage, which means that if A patient presented with a blind eye, we will probably not be able to restore vision. And as I always tell owners, it's not just me being limited as a veterinarian, glaucoma is a leading cause of blindness in humans and in humans too, retinal damage caused by, by glaucoma is irreversible. However, Please remember and please tell the owner that even if we are not going to restore vision, we still have to treat the patient due to the pain and we definitely have to do something about it.

Another important point is that secondary glaucoma, such as we are seeing here, may be cured if the primary causes resolved. So for example, if it is due to UVI, if it's due to lens laxation, successful management of UVIS or the lens lexation. Will resolve the secondary glaucoma and we don't have to continue treatment.

However, primary glaucoma does require lifelong treatment or surgery and really carries a poor long-term prognosis. When I, when I talk to my students, I always try and say this is the most important slide of my talk, and if you're going to remember just one slide, please remember this one. I'll say the same thing now, forget everything I've spoken about and everything I'm going to talk about, but please remember this slide here.

This slide says that primary. Glaucoma patients or patients with inherited glaucoma may present with unilateral disease. So the fact that this patient here showed with unilateral glaucoma doesn't mean that it's not inherited.

In fact, most cases of inherited glaucoma will present with unilateral glaucoma with the second eye affected an average of 8 months later. And therefore, when this patient presents in the clinic with unilateral glaucoma, please consider the possibility that it is a primary glaucoma. And when I say please consider possibilities of primary glaucoma, you should closely examine the eye to rule out secondary glaucoma.

So for example, look for signs of UVITs. There are signs of UVIis in this eye, that's wonderful because it means that it's secondary glaucoma and that this eye is not at risk. If there is neoplasia in this eye, it's wonderful news.

I know it sounds fine to say that neoplasia is wonderful news. It means that the glaucoma is secondary to neoplasia and that this eye is not at risk. However, If you're unable to find signs that indicate that this is secondary glaucoma, you should definitely suspect or consider the possibility that this is primary glaucoma and administer prophylactic treatment to this eye.

OK. And the reason you wanna administer prophylactic treatment to this eye is obviously, if you don't, 8 months from now, the owner of this dog is going to come back to the clinic. They, this eye has long been nucleated cause you've given up on it.

The pressure was too high. They'll come back 8 months from now and this eye will be blind due to glaucoma, and they will look at you and say, Doctor, could this have been prevented? And that would be a very, very horrible day for you.

And actually, the answer is no, it couldn't have been prevented because it's inherited glaucoma. This eye is going to get glaucoma no matter what you do. But if you did initiate.

Prophylactic treatment when this dog presented with the right eye affected, you are buying yourself an average of 2 years. So instead of 8 months, the patient will present 32 months from now with glaucoma in. The left eye and most importantly, when the owners come and say, hey, doctor, could this have been prevented with a clear conscience, you can look them in the eye and say, we did everything we could to delay the onset of disease in this eye.

What do we give? I'll come back to in a minute when we talk about drugs, but basically ophthalmic drugs against glaucoma either reduce the production of aqueous humour or they increase the outflow of aqueous humour and the choice of the drug will depend on the cause of the glaucoma. There are some cases like UVIis when, or anterior lungs taxation, when we don't give certain drugs, I'll come back to that in a minute.

And on the state of the angle, obviously, if the glaucoma is with an open-angle glaucoma, there is no point in giving drugs that open the angle cause it's open to begin with. But as I've said, prognosis for long-term management is poor. So what do we give?

Well, if it's a case of acute glaucoma, and when I say acute glaucoma, in some cases, the owners go to work in the morning, everything is fine. They come back in the afternoon from work and they find the dog blinded with glaucoma, a painful eye, a lethargic dog, a red eye, a blue eye with UVI with epister in. And with corneal edoema, they rush to the clinic, which you should administer is manitol intravenously.

The dose is 1 to 2 grammes per kilo and you say grammes, not milligrammes. You calculate the dose, administer it slowly over 30 minutes, and then put the dog in a cage for 3 or 4 hours without water because if You provide it with water, it will rehydrate, but basically the aim here is for the hyper osmotic agent to suck fluid out of the eye, out of the vitreous, and decrease intraocular pressure. Another emergency treatment that you could provide is paracentesis, in which we go with the needle into the anterior chamber, as shown here, we go in the limbus with a 25 gauge needle.

We do not connect . Syringe, we do not aspirate. We simply let one or two drops come out.

It's a procedure I did twice last week, and within minutes the pressure came down from 70 millimetres of mercury to 10 millimetres of mercury, so very fast relief. However, if you have no experience, please practise first using a cadaver before going with a needle into the anterior chamber. So these are two things you can consider as emergency treatment for patients with acute glaucoma, long-term management drugs we'd send the patient home with.

Our first line of defence or drug of choice with dogs is prostaglandin analogues. These are verificcacious because they increase the non-conventional outflow from the eye and therefore they will increased aqueous outflow even if the iridocorneal is obstructed. It's contraindicated in cases of UVIis cause this in uveitis you've got enough prostaglandins in the eye.

You don't want to administer more prostaglandins, that's like pouring oil on fire, and you don't want to give them in cases of anterior lens laxation because it will trap the lens in the anterior chamber and probably also incarcerate the vires in the pupil. Prostaglandin analogues is also something that you may give as emergency treatment, sit by the dog and put a drop every 1530 minutes. And in fact, the two dogs that I mentioned earlier in which I did synthesis last week.

First, we try a few drops of prostaglandin analogues administered over 30 minutes, and when that did work, we went in with the needle. Another drug, that I consider my second line of defence is topical carbonic drug inhibitors, also veryficacious because they decrease production, meaning that you can give them regardless of the state of the angle, we've got dorzolamide and brinzolamide which are given 3 times daily or coop and Azopt, which are topical carbonchondrase inhibitors with a beta blocker. Beta blocker reduces blood flow to the ciliary body and the blood is the substrate from which aqueous is extracted.

So you're decreasing the amount of substrate and inhibiting aqueous production, so double inhibition of production. Cats, well, you know, the cats are always more problematic. Our drug of choice, PGF2 analogues have limited efficacy in cats.

Some say they have no efficacy whatsoever because they lack the receptors. Topical carbonic anhydras inhibit. Therefore, are more commonly used in cats.

However, beware of systemic hypokalemia from these eye drops. I've had a case of that just last week. So again, be aware of this, complication.

And as I've said before, don't give atropine in cases of glaucoma. I mentioned earlier the importance of prophylactic treatment in the unaffected eye, and there is no consensus on which drug to give. You can see various studies evaluating the efficacy of Various drugs as prophylactic treatment in the unaffected.

I, here is actually a survey conducted among many veterinary ophthalmologists regarding the preference, really shows us that there is no consensus. Personally, I use toy carbonic an drug inhibitors. I saved the big guns, the prostaglandin analogue, .

For the actual onset of the disease. However, as I always say, what I think is important when you're giving prophylactic treatment is that the owner actually once a day goes up to the unaffected eye, administers a drop. This forces them to have a close look at the eye, and they can see very early signs of the globe.

Glaucoma, they'll come to you and say, hey, this eye is now slightly more red. It is slightly bluish, the pupil is slightly more midriatic. They will be able to detect the signs very, very early.

So as far as I'm concerned, they can even put tap water in the eye. It doesn't matter. What's important is forcing the owner to look at the eye closely once a day.

Unfortunately, as I've said, the long-term prognosis for treatment of glaucoma is poor and frequently it fails. We are left with a blind and painful eye which has to be nucleated. Many owners will say, ah, my dog is not painful, he walks, he plays, he eats, everything is fine.

What I always say is Consider the glaucoma to be a migraine. People with migraine also wake up in the morning, they brush your teeth, they go to work, they come back in the evening, they have dinner, they go out to the pub with friends. Yeah, they function just like the dog, but they are suffering constantly.

They are in constant pain. And frequently, when I give owners the example of migraine and When I win the argument, and I always win the argument, and I and I talked them into agreeing to nucleate the dog, they'll come back 12 days from now for suture removal, and the first thing they'll say is, wow, my dog is 5 years younger, cause they didn't notice the gradual onset of pain. They didn't notice the gradual loss of activity, but once you've removed the source of pain, the dog will Respond and the dog will be much happier.

You can see this study out of England showing that 96% of participants are happy with their decision to go ahead with surgery. OK? So please quote this paper, please tell the owners the analogy of migraine.

Now, I know that both for glaucoma and corneal ulcers, I've discussed two diseases that require frequent administration, but owners can't always give drugs very frequently. Sometimes you have this kind of a patient that the owners simply cannot approach and how can they treat the dog like that with glaucoma or with a corneal ulcer? And the answer is a subpalpibrlavi.

System that we usually use in horses but shown here in the paper out of England, that is being used also in dogs. So basically we are talking about this long tube that we connect to atrocar here. And it's shown step by step in the next slides.

Oops sorry. Yeah. So we are feeling the fornic here of the patient, and we insert the roar as you can see here, which is connected to a tube.

We pull the tube through, we pull it, we pull it until we get into This foot plate, which is embedded on the inner aspect of the lower eyelid between the globe, between the eyelid and the third eyelid, so that the cornea is protected. We fix it with a couple of sutures to the skin and the distal end of the tube has This corkscrew which you can open, administer the drug, push it with air through the tube, and it clicks onto the ocular surface through the holes in the foot plate, and this way you can treat this mean looking dog. Another thing you may consider for dogs that can't be treated frequently, if you have a dry eye patient is a subconjunctival cytosporin implant.

We know that yosporin is a drug of choice for patients with dry eye, but again, some patients can't be treated frequently and therefore, the University of North Carolina State University in the United States sells cyclosporin implants, which are implanted very easily subconjunctibly, just snip with the scissors, throw the implant in and place a couple of sutures. As I said, you can order them from the pharmacy of North Carolina State University. They'll send them to any country in the world.

Just when you go to their website, please make sure that you order the canine, sacrosporin implant and not the equine implant intended for the treatment of ERU equine recurring tuitis. Right. And the 3rd and final disease I want to talk about is feline.

Herpetic disease, feline conjunctivitis, and carato conjunctivitis. And the few things you should remember about treatment of herpetic disease in cats is that all of the available drugs are eurostatic, not vioidal, meaning you're unable to kill the virus. You are just your The aim in treatment is to take an active inflammation and return, cause the virus to return to a latent state.

Unfortunately, we do not have any drugs that can cure latency, so the owner should be aware of the risk of recurrence. Another very important thing is that many of these drugs require frequent administration and frequent administration in some cats may cause stress and stress is a risk factor in herpetic. Disease.

So actually with some treatments, you may be causing greater harm cause the stress you are causing may cause shedding of latent virus. So please consider carefully whether the inflammation is severe enough. In order to justify the treatment and usually we reserve the use of antiviral drugs for severe, persistent or recurring disease or the disease in which there is coronial involvement that proves to me that it is herpetic disease and not chlamydia or Calisi or anything else.

This article here is a review paper published by the University of California Davis. It's from 2016 but still the most comprehensive review of the antiviral treat drugs that are out there, . One very important point to come out of this paper is that all or most of the drugs that are available to treat herpetic disease are compounded by veterinary pharmacies or they are extra label use, meaning we are taking the human drugs and using them in our feline patients, and a word of caution.

Here, drugs that are very effective against human herpes are not necessarily effective against feline herpes. Case in point being acyclovir or Zovirax, which is a highly effective drug against human herpes. Here is a table showing IC 50 of various drugs against feline and human herpes.

And if you remember your basic pharmacology, the lower the IC 50, the more potent the drug is, and you can see that acyclovir or Zovirax is one of the most potent drugs against human herpes. It is virtually useless against feline herpes. So the fact that there is an anti-herpetic drug out there doesn't mean it will help your feline patients.

What drugs may help your feline patients? Wait, trifluoridine, that you're seeing here and doxoridine are two topical drugs available in many countries that are effective against feline herpetic disease. Trifluoridine may have better penetration but more expensive and more irritating.

This one is better tolerated and cheaper, so it may be preferable, but both of them need to be given at least 5 times daily. In order to be efficacious. And as I've said earlier, stress is a very, very important risk factor in the pathogenesis of ropetic disease.

And I challenge you to take my personal cat and treat it 5 times daily without causing any stress. So, you know, first time I may be able to grab my cat, put a drop in the app. In his eye.

2nd time I'd have to chase him to the other room to give a drop to the eye. Third time, I'd have to move the sofa cause he's hiding behind the sofa. 4th time I have to remove the refrigerator cause the cat is behind the refrigerator, etc.

Etc. And repeat it the next day and the next day without causing any stress. It is very, very difficult.

Therefore, we were happy when preliminary studies showed us that guncyclovir is very effective when given only 3 times daily, better than 5 times daily. Unfortunately, however, this was proven to be efficacious only in experimental herpetic disease when we are talking about clinical disease in Shelter cats, it was less efficacious, so not a drug that we can use or that I would recommend encyclovir. Instead, your life will be greatly improved if you have either of these two drugs available which are administered only twice.

Daily Sidofovir available as a topical solution, very well tolerated, very efficacious. However, it is not available as a commercial product. It must be compounded and it's very expensive.

In my country, it costs over $100. In the United States, I believe more. Not many owners are willing to spend that much on eye drops for their kitten.

Which is why many of us resort to hamcyclovir, which is given orally. Thamcyclovir is a prodrug of pencyclovir, which is metabolised into pencyclovir, and in the next slide, you'll understand why I am. Is that, because the metabolism in pharmackinetics are unclear.

We don't have a consensus on the dose for from cyclovir, but most studies suggest that it should be administered 90 milligrammes per kilo twice daily. However, as I've said, if the pharmacyobe is really a product of pencyclovir, which is the active ingredient against herpetic disease. And therefore, a couple of a few years ago, 5 years ago or so, my resident came up to me and asked me a wonderful question, really, this is a sign of a wonderful resident when you can learn from them.

So Oren Perer shown here. Came to me and asked me, why are we delivering the drug? Why are we delivering from cyclovir when we can actually deliver encyclovir to the eye, when we can actually deliver the active ingredient.

And I asked him how would we do that? And he said, well, it's easy because we've got pencyclovir cream available for the treatment of oral herpes in humans. So, I know you are surprised here as I was cause it's intended, this is a product intended for human neuropathic disease, and it's a cream, not an eye solution, but we have been using it for years.

We presented it in a couple of conferences and now have paper in press about it, and it is highly, highly efficacious. Yes, we take the oral cream, we put it in the eye twice daily or 3 times daily, try it, you would love the results. If you're as old as I am, you may have heard about lysine as an antipetic drug which may reduce shedding carriers and improve clinical signs, but really there is very little data to support it in client owned cat.

It's mostly in experimental cats, but It's lysine. It's an amino acid, so it is safe. You can give it 500 milligrammes twice daily as a bolus, meaning you don't sprinkle it on food, you need these chewable tablets.

It is regarded as an adjunct therapy, not a real drug for the use of, For the use in herpetic disease and interferon, something that we use in the past, but again, as the, we use it really without any evidence, and I quote the review paper for the UC Davis saying that there are no rigorous perspective studies showing the efficacy of interferon. What you don't want to give, as I said, is Zobox, which is ineffective in cats. Other drugs which may be efficacious in in humans may in fact be lethal in cats, and please do not give steroids cause steroids will activate latent herpetic infection.

As I've said, that's a big risk factor. How long do we treat these cats? Well, I would say we treat them until clinical signs have improved and another 2 weeks.

As I've said, we never cure herpetic disease. We just aim to return the virus from an active state to a latent state and therefore, we have to warn the owners that recurrence is possible, otherwise they'll be very upset with us. They can try because stress is such an important factor, in addition to all the drugs I've described, we should definitely reduce the.

Choice of patients, their pheromones and other substances out there to reduce stress, tender loving care with adequate nutrition, hydration, patient comfort, isolate affected cat. It's not because I'm afraid that the affected cat will infect the other cats. All cats are carriers of herpes.

I'm just trying to minimise the stress of the affected cat. By isolating it from other household cats and maybe stop treatment cause once again, as I've said again and again, very frequent treatment may actually be detrimental in that it triggers stress and makes the disease worse. So it's a very mild, if it's a very mild disease, maybe no treatment is the best treatment.

Many herpetic patients also suffer from dry eye cause herpes virus is a leading cause of feline dry eye, unlike dogs where it's an inherited autoimmune disease and therefore owners should clean the eyelid margins of affected cats and you should prescribe yuronic acid-rich artificial tears. If there are ulcers or if you suspect the presence of chlamydia or mycoplasma, you should definitely treat the patient with tetracycline cause it's very efficacious against these agents. We will treat corneal ulcers with tetracycline cause we're afraid of the ulcers deteriorating with contamination and we'll administer it in cases of respiratory disease.

So topical tetracycline, if you are and also systemically, we will use doxycycline, which is more efficacious than azithromycin. So to sum up, medical treatment of feline herpetic disease, as I've said, tetracycline should be used for suspected cases of chlamydia, which is usually young cats with microjunctivitis and no corneal involvement. Tetracycline should be used for corneal ulcers and respiratory disease, and Add antiviral treatment for the recurring conjunctivitis and severe corneal disease.

Please add artificial tears and please consider the possibility that in mild therapetic disease, no treatment may be the best option. I mentioned my beloved cat earlier. You can see that he's got slight problem in his left eye.

I know from experience that if I try treating the left eye, I am looking at A very lengthy treatment period, but if I just don't do anything, I don't induce stress and in a few days, the infection will resolve, the disease will resolve, and the virus will become latent again. So again, do no harm and remember that cure means establishing latency, recurrence is always possible. And because we're talking about drugs, the second most important, slide with which I'll bid you farewell is the topical anaesthetics are used only in-house to facilitate exam and procedures.

We never prescribe them to owners. You are presented with a painful eye, you put a drop of topical anaesthetic in order to facilitate your examination. Nation, the dog or the cat opened their eyes and the owners are shocked.

Wow, you have cured my patient in 5 seconds. No. Obviously, you haven't cured the patient in 5 seconds.

All you did was administer to anaesthesia and mask the pain. They will beg you for these magic drugs. I never ever give it to them because Frankly, as you know, pain is an important clinical sign.

We want to know whether the patient is improving or deteriorating, whether pain is receding or worsening, and we don't want mask it with topical anaesthesia and Even worse, they will keep it in the drawer and next time the dog has a problem, or God forbid, even they have a problem, they'll just put in these magic drops in their eyes and think that the problem has been cured. Never ever give them to owners. I thank you very much for your attention and I look forward to seeing you in the next webinar.

Have a good day.