Hello and welcome to this online lecture. My name is Ursula Dietrich and I'm very happy to share some key points on corneal ulceration in dogs and cats in this half hour lecture. The topics covered in this lecture will include non-healing ulcers as we see them in dogs and with a special form called SAT.

We will discuss progressive ulcers, the cause of progression. And what can be done to stop progression and of course viral ulcers, which we see those in cats caused by the feline herpes virus. I will discuss diagnostic steps for each of these ulcers and of course we will discuss treatment for each of those.

In order to understand corneal ulceration, we have to have a good understanding of the corneal anatomy. So this image on the right shows a cross section of a normal cornea in a dog with the epithelium on the top, with the underlying basement membrane, which is the barrier to the corneal stroma, which is the bulk of the cornea. And the decimous membrane and endothelial layer on the most inside part bordering the acres of the anterior chamber.

The precorneal tear film is a very important part of the cornea itself. It not just only lubricates the surface, but it also has antibacterial properties through lysozymes, peroxidase, and lactofein that can be found in the tear film. As you can see, the cornea is almost like a sandwich.

So having the epithelial and endothelial layer, bordering and protecting the stroma and preventing influx of fluid into the stroma. The precorneal tear film itself is composed of three different layers, which are shown on the image on the right. So the lipid layer is the most outer layer, preventing evaporation of the fluid is produced by mybomian glands in the eyelids of dogs and cats, the middle layer, the bulk, so to speak, made up of the aqueous, which is produced by the tear gland and of course, important as well, the third eyelid gland.

And then the mucus layer. Produced by conjunctival goblet cells, which is bordering and tightly connected via glycocalyx with the corneal epithelial layer. When we test the tear film in dogs, we use the shimmer tear test, which measures the basal and reflex tears and does not require previous topical anaesthetic.

So this is called a shimmer tear test one. In dogs, normally we would see a measurement of 18 and above in a normal dog. And if it's coming between 10 and 15 or below 15, we would be suspicious of an underlying ketoconjunctivitis Zika.

And of course the diagnosis is made if the sheer tear test result is below 5 millimetre per minute in the dog. In the cat, the tear film. Results of TMRt test results are usually lower.

There has been a few studies, but a more recent one showed in cats that probably an average reading would be around 14 to 15, but they also found much lower values in cats that didn't show any underlying clinical signs of KCS. Corneal transparency is absolute important for vision. And in order to have this transparent cornea, we have to have a very smooth surface.

We have to have a very orderly arrangement of collagen fibrils fibrils in the cornea as shown on this graphic on the right. So each of these black dots would represent a collagen fibrile and you can see how exact the distance is between each of those. Any disruption of disorderly arrangement would cause corneal opacity or cloudiness.

There is by nature no pigment in any cornea, in a normal animal. There shouldn't be any blood vessels or cells. The cornea is extremely poor.

There are few keratocytes found in the stroma, but otherwise mainly or largely acellular. And of course, as previously mentioned, the control of the water content is important and done by the epithelial and endothelial layer which keeps the cornea in a state of relative dehydration. So the good news is that corneal healing occurs relatively quickly in the dog and cat.

So the epithelium has an excellent regenerative power. Initially a small defect in the epithelium is covered through cell migration. So these cells slide over this defect and seal it.

And the underlying basal cells will duplicate and reproduce and usually the turnover of those cells is in about 7 days. So a small epithelial defect, maybe a scene on the right picture could cover easily within 24 hours and no fluorescent stain uptake would be noticed after this time. So the real problem occurs if an ulcer is not healing, and we need to find out what is the underlying problem.

And foremost, it is important to check on the tier film. Is the tier film, is there not enough acres produced? So is there a clear problem with the quantity?

So we have a kerato conjuncti IDCa as an underlying problem or like in this practise of alecdo here on the on the right, is this an exposure or a quantity quality problem of the tear film where the tear film is evaporating too quickly because of chronic. Exposure, the dog is not able to blink properly, so the tears are drying out too fast and causing the cornea to undergo significant changes like pigmentation, vascularization, fibrosis and ultimately corneal ulceration. Corneal mineralization can also be a problem we see particularly in older dogs, so these calcium deposits in the surface layers of the stroma lead to chronic ulceration that are very difficult to heal and very difficult to medicate down the road.

In addition, we would have to check for mechanical irritation that could be the cause of the ulcers. So is there entroium visible? Is there any dysticiasis in the upper eyelids or lower eyelids that could cause irritations and potentially ulcers?

Is an ectopic cilia present? Usually ectopic cilia are found in the upper eyelids, so we would have to look carefully avert the upper eyelids a little bit and check if there are any. Hairs present that could cause this, this, this ulcer that's not healing, or even a foreign body that may be lodged somewhere in the third eyelet that could cause a non-healing ulcer.

And if all these underlying causes can be ruled out and this is clearly a spontaneous ulcer occurring in this middle aged dog, then we very likely speak of a scared, a spontaneous chronic corneal epithelial defect. So here are some pictures to show some typical problems that may be underlying causes for non-healing ulcers. So here on the left, we have an English bulldog with chronic ulceration caused by kerado conjunctivitis Zika.

If we see dogs that have thick mucus, maybe mucopurulent discharge, sticking on the surface of the cornea, almost like chewing gum like in larger amounts. Crusting of the eyelids. Usually this is very significant and and typical for a dry eye disease.

So in these dogs, HTMRT test is utmost important to diagnose this problem. And on the right we have a dog, a West Highland white terrier, with coal mineralization. This is a calcium deposit.

The calcium usually sits in the more surface levels of the stroma, so it does cause significant problems with ulcers. Indolent ulcers, not healing ulcers that are very difficult to treat and may not be responding to any treatments. So very often in these dogs, they require a superficial keroectomy to remove this calcium.

And then another picture here on the left, this is a foreign body that is found behind the third eyelid, so it's always important. And advised to check the third eyelid inside and see if there's a foreign body that may may be causing this indolent ulcer. This is not a very unusual finding.

We've seen quite a few of those cases that were previously undetected and once this foreign body is removed, then the ulcer usually heals up fine. And then on the right side, we see a on the top, this is a dog with an ectopic cilia. So ectopiccilia and Dicia are both aberran cilias that emerge from the mybomian glands.

The ectopic cilias, they usually Come through the conjunctiva, people conjunctiva and cause significant pain and ulceration in these dogs and they can only be detected with magnification or litland exams. It's very difficult to see them. They require surgical removal.

On the bottom, you see a dog with dyschia. Dysia not always cause issues. They certainly are irritating the dog, but they're not always cause automatically ulcers, but yet they could certainly be a cause and if we see those, they need to be addressed, to eliminate potential mechanical irritation.

So let's talk about a case here. So this is Benson. He's an eight year old Labrador, and Benson had a chronic coal ulcer in his right eyes for several weeks.

He had intermittent plethora spasm and epiphora, but he's not overly painful in this eye. Previous treatment consisted of chlorophenic ointment and reman coal repair gel. But despite all this treatment, there has not been really any improvement.

So all his ocular parameters were tested. Hischier test was within a normal range, his pressure was in a normal range, and there was no underlying problem found. So the eyelid confirmation was was normal.

There was no foreign body detected. And as you can see on these two images, the fluorescene test, identified a very superficial ulcer. Close to the limbo lateral limbble area in this dog.

It's a little bit difficult to see here, but his epithelial edges were not very well adhered, so they were a little bit loose looking so there was some what we call under run of fluorescy in stain. The eye itself is relatively comfortable. There was no sign of, of inflammation inside the eye.

So, overall the eye didn't look too painful. Also, there was no sign of any blood vessel ingrowth or other corneal changes in in the dog. So based on the lack of underlying ocular abnormal anomalies, the cornicity of the problem and the presentation of this ulcer, which was very superficial, with loose epithelial edges, no corneal adverse reactions in the cornea.

So we were confident of a scad in this dog, a spontaneous chronic corneal epithelial defect. So what is ACCAT, which stands for spontaneous chronic corneal epithelial defect? So if we have another look at the anatomy of the cornea, so the epithelial layer on top of the stroma is the problem in these dogs.

So there is a zone, acellular hyenized zone found in the superficial stroma. And a missing basement membrane in these dogs as well as an abnormal corneal nerve plexus. So there are normally in a dog, we have a very you know, network of nerves, particularly in the anterior stroma and epithelium and in these dogs, this is missing or abnormal.

So if there is a spontaneous ulcer occurring, most likely initiated through trauma, these ulcers in these dogs don't heal up. They literally stay persist sometimes for months without any signs of healing, no vascular ingrowth, and typically the epithelium is loose and can easily divide it on the edges. So in previous years, these dogs, and particularly some breeds were more predisposed like boxers, hence the name boxer ulcer.

These are, you know, younger middle aged dogs where these ulcers suddenly can occur either in one eye or sometimes in both eyes as well. So, the key to treatment, most of these dogs, they will receive a various amount of antibiotics, etc. But nothing usually happens.

But the key is to remove this epithelium that is No adhered. So we call this debridement, and this can be easily done with a topical anaesthetic. Most dogs don't require any sedation or anaesthesia for that, and it's very easily done with a sterile cotton applicator that's supposed to be dry and we vigorously remove the epithelial letters until the corneal surface is nice and smooth.

The debridement is then followed by a so-called keraotomy of the exposed stroma. So what this what this should do is actually promote healing of the cornea by stimulating the ingrowth of blood vessels and growth factors and cells that are usually at the corneal limbus. And it can be done in various ways.

So in the old days, we used to have performed what we call a needle keraotomy, so in a form of a grid as shown on the upper right hand side, so in the form of a grid pattern, the needle was actually scratching the surface of the stroma. Most dogs, of course, would have to stay stay very still for this procedure and often a sedation or an anaesthesia was required, but using the so called diamond bird is probably a little easier because most dogs tolerate this very well, although there is a bit of a buzzing sound heard. But this little diamond bird is shown on the left is a very quickly rotating.

Head covered in in diamond crystals and it's quite nicely with a little bit of pressure. The entire affected area can be buried, comfortably. I would recommend to wear be very sterile, at least wear gloves performing this procedure.

There's always a risk of, you know, and bacterial infection afterwards. So ideally what we also do is, is, rinse these corneas with diluted betadine solution. So make sure this is all performed prior to doing a keatotomy.

So the placement of a contact lens after debridement and keraotomy is certainly an option. It's it's very helpful in some cases. The key is to is a good fit of these lenses.

Because they do tend to fall out, which the owner has to be instructed about. But I find the pure vision lenses, hydrophilic lenses quite, quite handy. They kind of like hold the surface well, they stick well to the epithelium and can easily be placed with a forceps, you know, plant forceps like the one that is shown here, which is the font grey of forceps.

So I I find this quite handy. This can be done again in an awake dog and the contact lens allows application of eye drops and it has a good oxygenation through the through those lenses to the cornea. The medical treatment is relatively straightforward and of course these dogs will require a topical antibiotic, usually a broad spectrum antibiotic.

The anti-ollainous treatment is particularly important if we deal with practise. Breeds. So I would recommend either or an oral doxycycline, which is not only an antibiotic, but also an anti coaggenase and supports corneal healing and serum or plasma can be applied in these dogs afterwards.

For pain relief, a few days after the procedure, a topical atropine can be given, which helps with the spasm of the ciliary muscle, so it does relieve pain after corneal treatment and of course some oral meloxicam is handy to give for a few days following the treatment. I also would recommend that these dogs wear a buster collar for at least a week until the recheck can be performed. Healing of these ulcers can still be slow, so the owner needs to know that this can sometimes take a week, sometimes longer.

The debridement or keratotomy may have to be repeated. So some breeds, particularly in the practise of phallic, we do see quite an intense neovascularization in some case in some some cases with granulation tissue formation, which can be quite significant. So these dogs will require additional anti-inflammatory treatment either through topical NSAIDs, or they can have optimune added, which also helps to decrease the blood vessel in growth.

It's also important to remember that if this treatment has to be done a second time and it's not healing, that sometimes aarectomy, where actually the superficial area is surgically removed under general anaesthesia, maybe the treatment of choice if the owner wishes to do that. It is luckily rare, but we do see sometimes an overreaction of the cornea after treatment. So this dog was presented after he had a keraotomy performed, and he presented a few days later with a completely melting progressive corneal ulcer.

It is not quite so clear why brachycephalics have this reaction. It's very likely a problem of their corneas, but they have a very high tendency to to get this type of reaction. So it is very cautiously done in these breeds and as mentioned before, I would absolutely apply serum or doxycycline in practise of phallic dogs after a keratotomy.

So what happens if an ulcer progresses? So why is this happen and what are the underlying causes? So, basically, There is an increased activity of matrix, metalloproteinases, like proteinases and collagegenases seen in the cornea.

So they are activated by numerous agents. It can be bacteria. It can be neutrophils in the cornea.

It can be the cornea itself because these MMPs of course play a crucial role in normal corneal healing. So in the epithelium, in the stroma, in the TFL. And what we call a melting corneal ulcer is a essentially a degradation of the corneal stroma.

So on this picture here, in this horse, this is very, you know, drastically shown here, but this. Higher cornea has started to melt in this area, almost drooping over the lid and this is a classical effect that may start very slowly but then quickly goes out of control like the snowball effect. So this is an example of a melting ulcer.

A progressive ulcer in a French bulldog. So the practicecephallics have a very high risk of this type of ulcers, and they can readily occur out of a superficial ulcer in no time. What we can see here on the picture is this ulcer is covering largely the axial cornea here, very soft gelatinous ulcer, melting ulcer in the middle.

And then the anterior chamber has a reaction. See hypopion here in the ventral anterior chamber, this kind of white accumulation of inflammatory cells and the cornea is quite cloudy, it is diffuse edoema, and we have intense conjunctal hyperemia and the pressure in the stalk is clearly very low if we would take the pressure check here. So these ulcers typically when they progress further, they do have quite a significant reaction inside the anterior chamber and this secondary anterior uveitis is triggered by nerve endings in the cornea that release substance P, which again releases poststag glandin in uveal tissue causing Typical signs of uveitis.

This axon reflex is present in. Any ulcer to a certain degree, but certainly becomes more significant when ulcers progress. So clinical symptoms, we would see on this do here would be a hypopion again in the ventral anterior chamber.

We have certainly flare, we have meiosis, there's diffuse coal edoema, there is conjunctable hyperemia, probably some mild chemosis as well and these dogs, if we measure the IOP have low intraocular pressure. So if we don't. Start immediately treating these dogs.

They are always an emergency. They can further progress until even perforation of the eye. So there are some significant pictures here of for example, so this one here would be a very large decimeto seal in this in this bulldog, at risk of perforating any time and then this dog, unfortunately, the ulcer has perforated and there's actually iris prolapsing.

Out of the eye. So these cases of course have a very significant risk of infection and blindness down the road. They can still be treated with surgical intervention, but the prognosis remains very guarded.

So prior to treatment of these progressive ulcers, it's always advised to take a culture swab, easily performed in most dogs, and this is very important, so we have an idea what organism is growing and what is the sensitivity spectrum, so we can adjust our antibiotic treatment. Also cytology is easily performed with a topical anaesthetic and these soft cyto brushes is shown on the left bottom. So these are very helpful to identify organisms right away so we can see if there are any fungi even present or what type of bacteria, cocca or rods and then kind of like helps us with the choice of the antibiotic.

So medical treatment is very intensive. It has to start immediately, even in cases that may require surgery at a later stage, but absolutely necessary are antibiotics that are either broad spectrum or according to the cytology, tailored and then depending on the culture. Initially given every 2 to 4 hours.

So secondary anti collaginases are probably one of the mainstays of these of these treatment of this treatment of these melting ulcers or progressive ulcers, and they can be applied topical in form of serum, which is then applied every hour or two. Plasma can be given instead of serum if that is not available. And doxycycline has definitely anti collaginase activities, so it is very helpful in these ulcers to add as a additional drug systemically given 10 mg per cake once daily.

Atropine is important, particularly if there is significant anterior uveitis, it does alleviate pain through the cyclopplegic effect of the atropine, so it does relax the spasm that is painful in the ciliary body muscles. And of course most dogs benefit from systemic anti-inflammatory, so meloxicam. Is important.

I would stay away from topical anti-inflammatories at that stage, and we can always add those at a later time, but initially they may be counterproductive, so oral medication is is preferred. And this shows the amazing healing capacities of the cornea. So this dog had a melting ulcer, initially an indolent ulcer that has been was treated with keratotomy, developed a melting ulcer.

But with very intensive medical treatment, the dog recovered, the cornea did not require surgery, but of course, if you can see, this is the picture the owner sent a few months down the road, there is still significant scarring in the cornea which may over time improve. The dog was also placed on optimmune long term, so this did help with the clarity in his cornea. If all goes bad and unfortunately, these ulcers sometimes still progress or they already have perforated, we have to consider surgery which is a referral reason.

The options here depend a little bit on the case scenario. It depends on the experience of the surgeon and the availability of the grafting material, but most of the time conjunctive grafts can be performed if they are too large. Of course, we usually opt for more visions sparing procedures as our corneal transplants that can be done with collagegenase biologic material like biocyst or amnion.

And so if you look at these pictures, so this on the upper right hand side, this is a large conjuncti graft performed. And then on the left bottom here is a full thickness corneal transplantation and the stock here on the right, bottom corner here has had an a cell performed a cell graft performed in the axial cornea. So you can see there's quite a significant vascularization occurring in these dogs, but with time, usually corneal clarity is achieved, but there will be in all cases after these procedures, there will be persistent scarring remaining.

So let's have a look at an eye case in a cat. So this is Alfie, it's a six year old male neuter domestic short hair, and Alfie presented with mild plethoras spasm and conjunctivitis in both eyes. He had those symptoms for a few days, but he also had a history of previous recurrent bouts of conjunctivitis in both eyes.

Those episodes were usually self-limiting. And did not require any treatment at the time. If we look a little bit closer so we can see the conjunctiva is quite inflamed, hyperemic and chemotic or swollen, as you can see on the on the image on the upper right hand side.

And then he also has this very fine linear, almost branching ulcers, superficial ulcers in both corneas. They are very weakly staining with fluoresce. What is also striking that the anterior chamber is relatively quiet and so there's no obvious sign of inflammation inside the eye.

So based on the history and the typical appearance of these ulcers that are fine dendritic branch like in Alfie. We are diagnosing most likely an underlying feline herpes virus infection. So because they affect very superficial layers, so basically essentially just the epithelium, they're very difficult to detect, particularly if the basement membrane is not breached and fluoresce cannot leak into the underlying stroma.

So then it is very helpful to use rose spangle, which is another Vital stain, but it does help to demonstrate devitalized cells and as you can see on this picture here on the right side you can see these branching ulcers clearly nicely shown with Bele rose. The herpes induced ulcers can also have a different shape. They sometimes may be larger, more geographic like ulcers, more like the dog's non-healing type of alterations, so with loose epithelial edges, superficial, they may persist for a long period of time.

And very little reaction in the cornea. There may be sometimes some new vascularization visible like on this picture on the left. But what is also important in these cats, similar to dogs, it's always important to measure the tear production, particularly in cats with underlying feline herpes virus infections.

We know that long term their tear production can be reduced. And so it's always important to check and see if these cats may need and benefit from additional artificial tears. The herpes virus is quite common in cats worldwide.

It can be very easily transmitted, particularly where cats are housed together closely, like in boarding facilities or caddies, etc. And is easily spread between cats. The feline herpesvirus is part of the upper respiratory disease complex along with other organisms like calicivirus, chlamydophyla, mycoplasma bordetella.

And kittens particularly are susceptible between the age of 8 to 12 weeks when their maternal antibodies are waning. So in these cats, the native infection often results in Fulmin and ocular disease like on this cat on the bottom right here, which has a severe corneal problem with slightly. Coal perforation and affecting this disease affecting both eyes and this is quite common in younger cats to see and if they survive, they may have long lasting effects and of course this virus persists lifelong in the body.

The virus has particularly affinity for cooler epithelial surfaces of the upper respiratory tract and of the eyes. It does not replicate if the temperature is over 37 degrees, so that explains that particularly the eyes and nasal turbinates are affected more easily. It occurs that during this infection, cytolysis and necrosis of epithelia is responsible for conjunctivitis, corneal ulceration, and particularly in younger cats.

Simple formation, which is an adhesion of the conjunctiva, either bulbar, palpiro or both with each other and with the cornea, sometimes also affecting the third eyelid lining. Which can lead to chronic tearing, epiphora, of course, chronic visual deficits and sometimes the nasolacomal duct is affected as well because of occlusion of the tia puncta. This image on the right is a in vitro picture of a epithelial cell culture.

With affected with herpes virus and you can see these large holes and necrosis and cytolysis that is occurring because of this infection. So as previously mentioned, the diagnosis of feline herpes virus induced ulcers is largely based on his story and the typical clinical presentation, particularly if there are dendritic ulcers present. However, it may be still helpful to perform a PCR lab testing to rule out other and maybe underlying or concurrent causes of conjunctivitis, which may be chlamydophila or mycoplasma.

So a conjunct scraping is recommended in these cats, particularly when they have a chronic or recurrent disease. So treatment of feline herpes virus induced ulcers are definitely requiring treatment with antiviral medications, so we can do this either as an oral applied drug in form of tablets. Compounded gels, fromcyclovir is the drug of choice.

It's usually administered in a quite high dose, so 90 milligrammes per kilogramme, twice or three times a daily is recommended. If this medication is not available, it is also quite expensive in the UK. We could apply viagany, which is available commercially.

This is gangcyclovir, which has been shown to be effective in in vitro studies and in vivo studies, and this can be applied 3 to 4 times a day at a minimum of 3 weeks or until all the symptoms improve. In addition, topical antibiotics may be helpful to protect the eye from further infection through bacterial invasion, so a broad spectrum antibiotic like clown finnacle is helpful. And in some cases, serum may be administered, particularly if the ulcer has a tendency to progress or is already melting, this can be added as well.

If the ulcer is geographic and large with non-adhered epithelium, it is helpful to debride these edges gently and potentially place a contact lens as this may help with comfort and healing in this cat. As mentioned before, the tear production is important to check and to measure. It may be reduced in cats with chronic feline herpesvirus infections, and it's always helpful.

In addition, if the er should be much lower than. Expected to start artificial tears, particularly hyaluronic acid based products are helpful and well tolerated, but also if the tear production is very low or even zero, topical cyclosporin can be quite helpful in cats as well. And this is the end of my presentation.

I hope you enjoyed it and I thank you for your attention.