Thank you very much for inviting me to take part in this amazing, virtual conference. This talk is about periocular and ocular neoplasia in horses. My name is, Derek Notenbelt.

I, am, a specialist in equine internal medicine and have a particular interest in neoplastic disease in general. So I hope this will interest you as much as anything else. Remember that not every lump, however, is a tumour, and there are a lot of other things that occur in and around the eyes, that are tumour looking and so there are a whole heap of these which exist in the eyelids such as collagen.

Granulomas such as you see here in the eyelid of a horse, mybomonitis, which you see here, calcinosis cutis, lots of other things including habernema in infections of varying descriptions of the eyelids. Similarly, the same appears in the conjunctiva, where we can see dermoid cysts such as the head dermoid here that you see, and of course lymphoid hyperplasia and again haberneiasis. And then within the globe there are a number of structures.

Which can be mistaken for neoplastic disease, including, iris cysts like this. And there are a whole heap of these which will come to, presently, we'll refer to them because they are really important in terms of the differential diagnosis of neoplastic disease. Neoplasia tends to have a more serious implication than, just an inflammatory lump or something that can be very benign, responsive or some congenital abnormality.

So all of these kinds of conditions do exist. And we need to understand those. So here are some of the others that could be mistaken for it.

So here's a, an nevus that you see here, and here's a melanoma. So you can see that this is an iris with a, with a nevus on it, a black nevus. There's nothing bad about it.

And here's a melanoma of the iris. So you can see that, and here's a melanoma within the globe itself, within the posterior chamber upon posterior compartment of the eye, which has filled the whole thing. Of course, the animal can't see through that, so the pupil is dilated.

The the pupil is also distorted as well as you can see. Here's a little adhesion, which could be mistaken for something going wrong. It shouldn't really be mistaken for it.

And here's some. Cysts, but there's a difference between this iris cyst group here. There's 3 of them on this horse which you see here, and this one here because this is a cystic granular eriddia as opposed to this, these ones here being genuine cysts, and you can see that is easily identified by ultrasonography.

So it's just to point out that not every lump that you see inside an eye is a neoplasm. Tony Stannard, who was a very well-renowned, equine dermato and histopathologist, pointed out to me many years ago at a meeting. He said, if you know what cells an organ or structure has, you will know what primary tumours it can get.

So if you know what structures there are, what cells there are within the skin, what cells there are within the cornea, you know what kind of tumours can occur there. And if you understand that, you can start to make some real progress. Of course, some tumours are very common, and others are very rare.

And rare tumours are only rare because they don't occur commonly. It's not that they don't occur at all. Now, objective has to be to try to divide tumours into primary tumours, in which case they can be benign or malignant, and secondary tumours or metastatic tumours.

So here you see a melanoma again of the ciliary body coming into this, into this intraocular space here. Here you see a carcinoma in situ of the cornea and here you see a sarcoid. Around the eye.

So we can have tumours in, on or around the eye, and the periocular region. So identify the primary problem if you can. So where you see things like this which may or may not be neoplastic, you have to try to, identify what the primary problem is and It's important to remember that this isn't always easy.

You've got to examine the case and you've got to examine the eye and the area in detail, and you've got to use whatever diagnostic aids are available to you. Of course you have an ultrasound machine, you can usually pick up something and this is an orbital lymphoma behind the globe, as you can see here, all this is. Tumour here.

And, so that's an orbital lymphoma, and here is a, extra adrenal paraganglioma which has destroyed the eye area here and the orbital bone and actually invaded into the nasal cavity and actually into the calvarium as well. So, So you can see that you need to make these diagnoses by examining the case extremely carefully. So this is the same horse as this, and this is just an abscess and this is a lymphoma.

So you can see there are, there are different kinds of things that can occur and you have to. Them. So, looking at this here, this is the consequence of an orbital mast cell tumour, a very unusual tumour, but just starts out in the eyelid and expands into the orbit and you can see there's a lot of edoema around.

Now, the edoema is not a primary part of the tumour. It's a consequence of the tumour. This is a malignant lacrimal gland carcinoma, very rare tumour.

You won't see many of these in your life, I don't suppose. Conjunctival mastocytoma, mast cell tumour. In the conjunctiva causes swelling of the upper eyelid, giving a firm non-edematous swelling, and then of course you've got this undifferentiated conjunctival myxocarcinoma with orbital bone destruction, a lot of blood coming out.

Horses shouldn't cry blood, you know, they shouldn't have blood in their tears, and the same applies. To this conjunctival squamous cell carcinoma here. So just look and remember that the initial presentation for ocular, periocular or orbital neoplasia can be very misleading.

So your major considerations are, of course, to identify the tumour type in full. The implications for the prognosis, of course, is depend upon what kind of tumour it is and, and the evidence that we have for that kind of tumour in that location. So, clearly, there are some tumours, as we'll see in a minute, that are very serious and some which are Serious, but for the most part, anything that occurs in and around the eye either has a primary harmful effect or perhaps even a prominent secondary effect which can also be functionally or actually life threatening.

The anatomic location matters. Where is it? What is it?

So here you see a carcinoma of the conjunctiva with secondary metastasis into the floor of the guttural pouch of the ipsilateral side. So this is the first drainage zone, lymphatic drainage zone is the diffused tonsillar tissue on the floor of the gut. Pouch.

And so that's where we would look in case of an eyelid carcinoma. He has some more tumours here. He has a melanoma, melanoma again, and of course, these are some of the facilities that depend upon the options which are available to you for treatment.

So if you have very sophisticated Equipment and so on, and a lot of experience, you can do a lot more perhaps. So, the, the patient and the owner compliance are important. You, it's all going to cost.

That's an inevitability, and it's going to be logistically challenging in, in addition. So, The treatment requirements are going to vary with your facilities and expertise. So are you going to be expected to treat the horse at the stable yard?

Can you hospitalise it? Do you have a hospital facility or are you a specialist centre? And all those range of things are available to all of us.

So, maybe that horse can't transport, in which case you have to do it. Maybe the facilities are very good and the horse is expensive and insured or whatever, and the owners don't mind whatever the cost. They want the horse sorted and then of course you have to have some specialist facility to send the animal to for that treatment.

There are lots of different tumour types in the periorbital skin. What is a tumour? Well, a tumour is just a swelling and that's what tumour means.

But actually we mean it, we take it to mean cancer. We take it to mean a neoplasm. So a papilloma like this doesn't really classify.

So this is viral papilloma here and here, and this doesn't really classify, but it's still a swelling and it's still a proliferation and it's still misleading, particularly in terms of its differential diagnosis. Melanoma, another Very common tumour type in the periorbital skin, sarcoid, of course, as you see here, fibroma or neurofibroma, 3 tumours related to fibroblast proliferation. Squamous cell carcinoma, very, very common, increasingly common in Europe, with climate change, I think it is really becoming a serious issue and we see more and more.

These over the last 15 or 20 years. Historically, of course, in very hot climates is where we would characteristically see these in non-pigmented eyelids and non-pigmented third eyelids. So these are all available to you.

Lymphoma again, unusual but important mast cell tumours, unusual but mostly mistaken. We'll come back to those and then, of course, these mysterious mixoma tumours, which are usually very destructive. The adnexy structures, of course, you know, have a, have that panel which we've just dealt with.

In addition to that, I've just added on here hemangiosarcoma, but the orbital structures have their own set of, tumour types, and they, they are different. Why? Because there's different tissue types present.

Different cell types present. So if you remember any cell that is present, you can make a case for a primary tumour of that particular type of cell. So here we have the lacrimal adenocarcinoma.

We have the sinus adenocarcinoma with extension from the sinus area into the orbital region. And, so this is the orbit and of course, then the same applies to the globe itself where there are different kinds of cells and different distributions in addition. So the first thing we want to try to emphasise is to know your enemy.

You need to know your enemy. And so here you see the two eyes of the same horse. You can see that this has a melanoma here, it's very characteristic appearance and probably another melanoma here.

Here you see a carcinoma, and here you see a sarcoid. So you can see this little guy has the full monty on the left side, but he As a melanoma and a carcinoma on the right side, so a little carcinoma on his third eyelid as well. Why?

Because it's non-pigmented, so it's liable to carcinoma. But is that the case for melanoma and sarcoid? Probably not.

So here you see another set of cases. Now, which, which are they? What are the tumour?

This is a lymphoma conjunctiva lymphoma, single tumour. Presented. I don't know quite how the owner noticed it, but the single tumour was presented.

Actually, there were 6 of these underneath this, so you had to track them down and follow them down because they all needed to be removed. Once they were removed, no more problem whatsoever. So it doesn't really fit the normal conventional lymphoma diagnosis.

Here we have a melanoma and here we have and here we have small areas of sarcoid, sarcoid, sarcoid, sarcoid, melanoma, lymphoma, all associated with this. So it's a question of knowing your enemy and that you need to make the diagnosis for each particular type of tumour because there are differentials for each type of tumour. So how bad is your enemy?

How, how strong is your enemy when you've got it? So, well, we, there's evidence for most of this and of course we, we need further information because simply because we say this is a squamous cell carcinoma, it doesn't mean that it's necessarily terribly bad. Maybe a superficial in situ carcino.

Or it may be much more serious. And this particular case shows, shows that this is the carcinoma here. It's the same case as here.

This is taken close up. And when we looked at the cornea, we could see that there was a seeded tumour here. And of course, that correlated with the fact that this carcinoma had gone round and through.

The, the third eyelid. And you can notice that this third eyelid here is pigmented margin, and that's unusual to have a carcinoma under those circumstances at this particular point anyway, but of course, it's a much more aggressive tumour further back. So when we look at this histologically, the the pathologist is gonna tell us what kind of tumour we've got.

Is it well differentiated, like this where there are keratin pearls, but should this Conjunctiva here have keratin on it. Well, no, because it's a non-keratinizing squamous cell. Epithelium and the same applies to the cornea.

There should be no keratin, so this represents a progression from normal, whereas here, of course, there's no keratin and the cells are totally undifferentiated. These are malignant cells. They're dividing cells.

They're abnormal cells. This is the manifestation of a really serious malignant tumour, and that has an implication for dissemination, of course. In this case, it looks like a carcinoma.

It was presented to me as a carcinoma, but it didn't look like it to me. I thought there was something odd about it, and sure enough, this turns out to be a mast cell tumour. Now if you take a scraping from this cell, from this tumour to have a look at under the microscope to see if you can see what kind of cell it is, all you get is xinophils.

Why? Because there are power-packed earxinophils in this area in a more cell tumour. Mast cells seem to attract the, the, the, opals and vice versa.

So here you see the tumour which has been stained with, with a specific stain for mast cells, or toluidine, of course, and, and you can see that here, and they've stained up and these are very abnormal mast cells. So this is a mast cell tumour. In spite of the fact that there were a lot of a lot of ears in a false present.

Easy to mistake for an ear xenophilic granuloma or something similar to that or even a, a habernema granuloma type of, of, of lesion. So these are the. So again, what about things that occur like this?

So now here we see this particular kind of Displacement of this of the third eyelid, and we look and we fortunately get access to a, to an MRI scanner and you can see that the tumour has filled the orbit and it's pushing the eye out of its position. And then when you look at it, in terms of morbid histology of pathology, you can see. That the tumour surrounded the whole of the orbit itself.

So again, this is a lymphoma and this is an extraadrenal paraganglioma. And so this was presented with exothalus, a visual eye with exothalus, as you can see. And when you look at that, you can see that this is under an MRI.

Scanner, a CT scanner, and an MRI scan. You can see where the tumour goes and you can see how destructive the tumour actually is. So all this is if it's available to you, you can use it, but if you know what your enemy is, then you've got a good idea of what the evidence base is for their management.

So rare tumours are just rare. They're not impossible. And so this is always the case, and this is a very interesting tumour.

It's a meduar epithelioma or retinoblastoma. So, as you can see, it's got this very fleshy appearance here. It doesn't look like anything, you know, it doesn't look like anything I've seen before.

Seen a few of these over the years. Notice that it's also actually interestingly enough, has a, an iris cyst as well. So, But when you look at the gross specimen and you scan it, you can find that the tumour occupies the whole of the orbit.

Actually, you can't see the fundus at all simply because it's occupied by the whole tumour. Here's the piece we're looking at. Here's the piece that there is inside.

This is a very aggressive tumour and of course if you look at the evidence, they all say that you can remove this and it's OK, but actually, It's much more complicated than that, and if you don't see them early and treat them early, you do land up with this circumstance. You can see the eye has been removed. This is the eye, and then 6 to 12 months later this is what appeared, and this is the same tumour as this.

So it had already escaped out of the eye, but it's hard to see where that happened and how it happened. We've no idea. Maybe it spread to a local lymphatic focus or something and then into the tissue, but nevertheless, it caused a lot of problems later on.

Diagnostic methods available to you. Well, there's a lot of things. You can look at something and say, I think it's that.

So when you come to a squamous cell carcinoma like this, you, these are the two eyes of the same horse, slides, supplied by Sheila Crispin, very kind friend of mine, and she gave me these slides to show you because here you see there is a carcinoma and this is the white eye of the horse. The black eye of the horse has nothing, so you can infer from that that it's likely that this is a carcinoma and of course you would be right because there's very little alternative. The cytology, which you can take from scrapings and so on, are quite hard to interpret.

You know, I, I, I leave this to a, to a pathologist. I'm not interested in trying to do this myself. Well, no, that's not true.

I'm interested and I'll have a look and I see, and then I try to understand what the pathologist has said. When I'm looking at the slide that I've retained, do I see the same thing? Can I learn from that and make my job a little bit easier and a little bit better?

Then you can biopsy these tumours, of course, you can take pieces of them, either by partial portional biopsy, a little piece of tumour tissue. Or you can do fine needle aspirate, really only suitable for melanoma. In my experience, sarcoids, you can try, but actually, you just land up with fibroblasts and you can't tell whether they're normal or abnormal.

You can do an excisional biopsy that's very commonly done for the third eyelid where you say, I think it's a carcinoma, I'm going to remove the whole third eyelid and I'm gonna submit it for histology. that's good. Interestingly enough, if you put Rose Bengal on these tumours, they light up like a stop sign, you know, like a brake light on a car.

They, they, they're very obvious when they're like that. And of course, there's a reason why that stains that area. You can use ultrasonography if you're worried about something inside and around the eye.

You can do radiography, CT and MRI if those are available to you. Realistically, They're not available to all of us. And furthermore, I think they're probably such specialised stuff that we need to, to manage those in a different kind of.

Use your aids. So when you know what you're dealing with, the prognosis and management decisions become easier. So here's our case which we described before, a little sarcoid here as you can see, but it developed a carcinoma distorting, really aggressive carcinoma and within the guttural pouch, these are the pictures that We took.

So you can see that in the guttural pouch, there were a lot of metastatic signs with big aggressive tumours and the lymph nodes at the back were in fact also enlarged. We didn't sample those, but you didn't need to because this tumour here could be easily sampled with a little biopsy instrument, comes up with the same thing as this conclusion. It's metastatic.

It's spreading, and has it got further than this? Almost certainly. How long does it take to manifest?

Anything up to 5 years. So you can see that it's important to have this extra information. So use all the the the aids you can.

As far as ophthalmic neoplasia considerations, of course there are different sites where they can occur, as we said before, so periorbital skin, the eyelids, lacrimal and tarsal glands, conjunctiva, nasolarymal duct, globe, and that's divisible into the cornea, the iris, the fundus, of course, and the orbit. So again, What cells are present in these structures and what tissues are present. And then, of course, you come to the panel of signs of clinical tumours that we encounter in general practise.

And these include sarcoid, squamous papilloma, melanoma, squamous cell carcinoma, not quite the same thing. This is a precursor to this one, of course, and then lymphoma. Not common, but common enough.

Mast cell tumours and then the rare tumours hemangioma and hemangiosarcoma, myxoma, meduar epithelioma, and astrocytoma of the retina. These are all very rare, and you, you can be mistaken. You can be forgiven for mistaking these, but I hope that you will always consider what tissues are there and therefore what primary tumours can occur there.

So firstly, we'll just have a quick look through periocular and palpibral sarcoid because this is by far the commonest periocular tumour. All 6 forms, there's 6 forms of the sarcoid, as we all know. All 6 forms are possible here.

That ranges from the occult ones, the very light ones, right the way up to the malignant ones like these. And of course, you've got to be careful of localised nodules because they can be mistaken easily for other things, both benign and other potentially malignant tumours. So the therapeutic limitations of the eyelid, of course, things that occur in the upper eyelid like this are much more dangerous than tumours that occur in the lower eyelid.

And here we have a tumour that's a very complicated malignant sarcoid of the upper eyelid that was Moved surgically with considerable success, as you can see. So it got through that, but it did have concurrent chemotherapy at the same time to try to make sure that we get the best possible chance. However, if you make a mistake with this surgery and you do not do it properly, then, of course, you land up with a cicaized upper eyelid, and that is a case where the horse has contracted its upper eyelid into a badly performed surgical intervention.

And has resulted in a failure of the blink process. So this horse suffers from persistent dry eye, persistent exposure, keratiti and conjunctivitis, and of course that had to be corrected surgically by putting a skin graft in the upper eyelid. It didn't function after that, of course.

That's because the invasive nature of upper eyelid sarcoids is World famous. It's going to happen everywhere and you must remember that they invade the upper eyelid and as a consequence, surgery is very often not successful on its own. So if you remove the whole tumour, You remove the muscles of the upper eyelid, in which case you get a bad scar and a non-functional eyelid.

If you don't, you may remove the tumour. But you end up with a secondary consequence that may even be worse, or You don't remove the tumour because you want to preserve the function and the tumour comes back worse than ever. So you can see it's a very important aspect altogether.

So here are some examples, see different kinds of tumours that occur around the eye, all very characteristic of sarcoid. So you can see multifocal areas of mixed sarcoid with different kinds of sarcoid, invasive sarcoid of the upper eyelid. And this very varicose or occult changes in the surrounding area, very extensive involvement here.

What's the key to this? Invasion of the upper eyelid musculature. So that's a key.

Of course, it invades in the lower eyelid as well, but it's much less important because the blink is not with the upper, with the lower eyelid. It's 95% with the Upper eyelid in horses. So this is important.

Here's some more examples. You see different kinds of tumour occurring here, different extents, different severities, different involvements, and here's these little guys, the flies here. They are quite important, as you can see here, and you can see sometimes very aggressive tumours with fibroblastic nature.

Which one's worst? Well, frankly, none. They're all bad.

There's no such thing as a good thing. Now here's the thing. If you see a sarcoid in the eyelids of a horse, be careful.

Do not assume that they can just be removed. It's easy to do, it's tempting, isn't it, to remove them. But remember, invasion, invasion, invasion.

That's the most important thing in the upper eyelid. Management, well, there's lots of treatments for the upper eyelid, or eyelid and, sarcoids in horses. Benign neglect, very unwise.

What does a tumour do? Tumours get worse, they become bigger, they become more aggressive, and they become more dangerous with time. So, the surgical removal, of course, can be problematic as we've explained already.

Here you see a failure of surgical treatment, very a catastrophic outcome from a really small tumour that was removed. Here you see failure of topical treatment where the inappropriate medication has been applied and landed up like this. What can you do about this now?

Very little about either of these two cases. This needs radiation, this needs euthanasia, of course. So, but this is a good example of what you can achieve if you are careful and you do have all the facilities.

This is radiation treatment. So there are 40 different treatments for sarcoids, none of them is 100% effective. And that's why there are 40 because you have to select different treatments for different lesions under different circumstances with different histories.

So all of this is an important issue for sarcoid. So, you know, think before you act and always use the best. Method first.

I can't go into all of these because it's not possible to do that in the time that we have available because we've got a lot of other tumours to do. But remember that this is the one tumour type that is intolerant of the wrong selection of treatment. If you select the wrong treatment, it'll go wrong.

You select the right treatment, it has at least a chance of doing right. And remember, it's always better to do a little bit more and be a little bit more aggressive and a little bit more advanced and have a chance of success than it is to play with them and have a certainty of failure because failure is very bad news. So here's a typical example of a horse that had multifocal treatment, a lot of treatment went into this horse, including radiation and surgery.

So here you see the surgical intervention followed by radiation and chemotherapy and of course at 14 months. It's not bad. All right, it's not elegant, but it's not bad and the tumour is controlled at least whether it's gone.

Don't know, but actually we should be suspicious of it. Other treatments, lots of other things out there that are used. The AW 5, or AW4 as it was, now AW-5, intra-legional.

Cisplatin, carboplatin, you know, in slow release form, electro chemotherapy requires 6 general anaesthetics at intervals. Not sure that many horses can tolerate that very well, but it's widely used and increasingly used regrettably through the United Kingdom, mostly because I don't believe. Does anything that is not equally done by one of the other systems and why give the horse 6 general anaesthetics or 5 or however many you need in order to solve a problem where it doesn't need any really.

I, I just have a slightly uncomfortable feeling about this was a machine looking for a job, not a job looking for a machine. Matamycin C slow, slow release polymer, 5 fluorouracil, tazarin, miquamod, Aldara, bloodroot, not around the eyes, AW5, not around the eyes. We would never treat them around the eyes with this.

And then there are a number of other dubious materials, of course, rubbish in a jar, all the homoeopathic nonsense that goes on. Acupuncture and so on is, is irrelevant. I just asked people what, what would you do for a cancer on yourself of a similar nature?

And certainly the acyclovvia story, we don't use that anymore because it has been proven to be ineffective. Squamous cell carcinoma, precarcinomatous changes are very common, where they're very small squamous papilloma like this, but then it transpires it develops into this kind of tumour. So there's a pre-carcinomatous stage, for all the conjunctival and palpibral carcinomas, and then there's a proliferative stage and then an ulcerative or destructive stage.

And sometimes they just move straight from one to the other. So you can have a Precarcinomatous change with straight into a destructive form, and you can see that it's a combination here of a proliferative stage, which is happening here and a destructive phase here. This is all destructive.

This is all proliferative. This is a squamous, a squamous papilloma precursor to, the carcinoma development and a lot of these are due to viral papillomas, at least that's the hypothesis. Not so sure myself, but nonetheless, it is, quite a likely correlation at least.

So here you see a squamous papilloma and a carcinoma destructive carcinoma on the same horse. Here you see a highly destructive, highly invasive carcinoma of the upper eyelid, very difficult to deal with, of course. This horse was an interesting one, has this very characteristic, pardon.

This horse has a very characteristic, ocular discharge, it's very characteristic, very like a worm sitting there. And, and owners and regrettably, some vets believe this to be infection. Well, it's not infection actually, it's a consequence of all the keratin being produced by the carcinoma.

So you look at this as Here for a long time. This has been present for a while. Nobody attached very much significance to it, but of course, as soon as you turn the eyelid out, you see that it's got this invasive carcinoma underneath.

Unless you get rid of that, you're never going to get rid of this characteristic discharge. So that's the panel of squamous cell carcinomas here is a proliferative one. And again, why has it got this sort of scaly appearance on it.

Well, that's keratin. That's keratin being produced from the outside. And so that's why they have this rather uncomfortable sticky scab on the surface.

Just keratin, when you peel that off, they bleed quite heavily, but you can see that this carcinoma has invaded all the way along the eyelid up to here and all the way up to here. This is still carcinoma running here, as you can see. This goes all the way back to here.

Of course, that requires a surgical intervention. You've got to remove that surgically. You've got to use concurrent chemotherapy such as topical mitomycin C or topical 5 fluorouracol drops in order to control this.

Of course, you can radiate it as well if you've got a strontium plaque that you plug into your cigarette lighter in your car. Not many of us have that. So here you see an invasive carcinoma, conjunctival carcinoma, which affected the nictitans and the ventral palpibral conjunctiva.

It eroded away here. And what did it do? Well, it destroyed the nasolacrimal duct.

So of course, we got a lot of tear overflow here, not only from the inflammation, but also because of the obstructed duct. Here we see a lateral limbal carcinoma. Here you see a carcinoma in situ, which we dealt with before.

Little bitty, and here we see this transfer into the carcinoma in, in situ on the cornea from the from the conjunctival tumour on the third eyelid. So you can see there, again, there are several different forms of this disease. Here's one that affected the, the nasolarymal duct and the punctum of the, of, of the eye of the, of the, of the medial, the area in the middle of medial canthus here.

So here you see this chauncle, the chauncular carcinoma, but it also affected the nasolarymal duct actually, all the way down. Was also to all carcinoma, was very difficult to treat with topical treatment, through flushing of the both retrograde and, and normal grade from the palpibral conjunctival, palpibr palpibr punctum of the nasolarymal duct on both upper and lower eyelid. Here you see an invasive carcinoma, very proliferative, very strongly.

Remember what we said, this can be proliferative or destructive or both, and this is the proliferative form. Here you see a very superficial one. Here you see a much more aggressive one.

Here you see the carcinoma in situ, and although this occupies most of the cornea, and the temptations, oh, we must remove the eye. Actually, you would never remove the eye. You would remove the carcinoma and treat the area.

They very, have a very prominent blood supply and they're very easy to diagnose. You can just take a scraping or even a biopsy from them. Yeah, these kind of things are clearly disastrous.

Disastrous carcinoma that's destroyed most of the upper eyelid as well. Very unusual because it's a pigmented eye, as you can see, it's a black eye, and that would be very unusual. Diagnostic methods, well, again, we're going to look at them and say, yup, it is.

We're going to do cytology, biopsy. Or ultrasonography, we're going to do all that. We're also going to scope them in the guttural pouch on the ipsilateral side, particularly for the longer standing or more aggressive lesions.

Remember that malignancy is not a question of duration, it's a question of all the other things that go with it. So you can stain them with rose bengal. You can do the lacrimal occult blood test simply by taking a urine dipstick, cutting it off at the blood square, touching that onto the conjunctiva and onto the accumulated tears in the corner of the eye, and, you'll see that it comes up positive for blood.

They should not bleed into the eyelid, into the, into the tears, so there's a problem. And of course that will happen with conjunctivitis. But if you are worried about a proliferative mass, then this usually means that it's got a carcinoma and it's a very impressive rose bengal stain for a carcinoma.

You can take scrapes and of course you can. Identify this. It's a matter for a histologist, I would suggest.

These are some that I've taken here. These have been stained with Papanicolau stain and are magnified to 100, and you can see that there's a dividing cell here. There's bizarre cells, abnormal cells, some big ones, some small ones, some dividing ones, all abnormal.

here. So those can be identified. You can take biopsies and the pathologist will tell us a lot about the biopsy.

We've mentioned this before. Remember, however, that there are very commonly lymphatic nodules in the eyelid margin. But this is the car.

Up here and these are lymphatic areas which are very reactive of course under this circumstance. So it's important for the pathologist to tell us whether we are dealing with a benign tumour a tumour in situ carcinoma, such as it remains. Within or outside the basement membrane or whether it's a malignant tumour and has some destructive capabilities.

So here you see a squamous papilloma on the eyelid and this is how it looks. It's just a squamous papilloma precursor to cancer. It doesn't matter about the pathology, it's just interesting.

And here we see a Squamous cell carcinoma of the third hylid. So and the histology is very different as you magnify it up more and more and more, this becomes more and more abnormal and you can see these abnormal cells here, lots of dividing cells, very aggressive potentially small tumour on the third eyelid. Very aggressive.

Size is not equated with malignancy. Here you see another one, very aggressive tumour. It's a keratin on the outside and the carcinoma inside the, the area with all this tumour dotted around in about.

There's another one. There's a, that's one of the lymphoid follicles, and they, they do look very aggressive and very often mistaken for lymphoma. They're not.

They're reactive and they're very commonly associated with surrounding carcinoma. Treatment options. Well, it's best not to leave carcinoma.

Carcinomas are bad if you leave them. Surgical excision is important. Cryosurgery is possible.

You can freeze little local areas. It's fine. Even on the cornea, you can do it.

You'll be careful. You need to be very, very careful if you're going to. Do that, but it's possible.

And then chemotherapy, we usually use 5 fluorouracil or Mitomycin C, and prednisolone, of course, as a very useful adjunctive treatment. Radiation, of course, the gold standard against which we measure all tumour treatments. Combinations are better.

But remember that BCG doesn't work. In cattle it works, so you'd never use BCG in cattle. I'm sure you understand why, but nevertheless, it would work if cows get carcinoma.

They do respond quite well to BCG, but horses do not. Topical therapy, 5 fluorouracil, these are all anti-mitotic, you know, they, they're dangerous, you know, you've got to be careful and so if you're giving it to owners, you've got to give them proper instruction. You know, you, you can't just give it to them and tell them to get on with it.

The realistic position, however, is that we can't do twice daily treatment for 6 weeks in a hospital because it's simply not possible. And so there are lots of different kinds of ways in which we can administer these chemotherapeutic agents and remember that corticosteroids are very valuable again. So either carboplatin, I don't use cisplatin anymore.

I think it's not a sensible thing to do. and we use intralesion or slow release injections made in an emulsion and injected subconjunct ole. This works quite well in a lot of cases.

Same withittamycin C polymer. Surgical excision, you can remove the surgically, of course, by removing the third eyelid. Please be careful when you do this.

It's, it's done badly in the most part, so that the gland of the third eyelid is removed. So, meticulous surgery is important. You know, you've got to be careful with this.

You've got to try to understand what you're doing. So, but this keriectomy, the superficial chaotectomy, is a very elegant bit of surgery and it looks terrible when you have to start it, but actually it's a lot easier than you think because most of them are intracorneal, intraepithelial or carcinoma in situ and therefore you can peel off the epithelium and the tumour goes with it. But Every single sample is submitted for histology to prove whether you have a safe margin or not, and every single tumour is managed with adjunctive chemotherapy.

I don't care if it says it's margin is safe or not. You have to do that because if you don't do that, I think you're asking for trouble. Radiation works either by strontium plesiotherapy, plesiotherapy, which you see here going on on a, on a lateral limbal carcino it's similar to this one here.

And we've got this strontium plaque here, which is pushing out beta. Beto radiation, which, which is very good for corneas because it's only very shallow and stays superficial. On the other hand, you can radiate them with wires.

This is LDR radiation with iridium wires and you can see from this To the radiation wire going up close to the tumour and then this is the consequence, very impressive result with a total cosmetic, an amazing cosmetic consequence, of course, affected the nasolarymal ducts, so there were some tear gland, tear overflow epiphera coming from the eye. Adjunctive therapy, of course, we do a lot of that to avoid sunshine, of course, it's important because you don't want to make it worse by doing that and you don't want new tumours. So, you know, what do we do when we see pre-purchase examination, non-pigmented eyelids?

Do we, do we warn the owner that there's a risk or do we not warn them and just hope that it doesn't do that. That's a debatable point, of course. Prednisolone and betamethasone are very useful adjunctive treatments.

Periocular and ocular melanoma, very common in grey horses. They occur in all sorts of places. Here you see one inside the eye and one in the eyelid itself.

Here's one in the eyelid. Here's one in the upper eyelid. Remember what we said about upper eyelids, upper eyelids much more dangerous than the lower eyelid.

But the, the intraocular melanoma is usually very benign. The outside ones, you know, they are non-malignant at the start, so they're better. Excuse me, dealt with when they are at the very earliest stages.

They are often at others at other sites, but not always. They can be single solitary lesions or they can be multiple. And again, here, the adnexa ones occur in these four sites here and the ocular ones occur in these sites here.

So the intraocular ones clearly, clearly have a much different implication altogether. The periorbital ones, these are the ones that occur in the tissues around the eye. So here's a melanoma, here's an upper eyelid one.

He's one in the orbit that's penetrated around into the, into the conjunctiva and into the upper eyelid itself. And here's a nice, well-defined one here. So the size matters.

So the Size matters, but there are secondary consequences depending on where they are and what happens. So what treatment you apply if you're going to remove the upper eyelid, well then there's going to be a consequence. On the other hand, you're going to try to remove a lower eyelid.

It's very easy surgery to do accurately and you get a good outcome. Intraocular melanomas like this very dangerous. Be very careful before you say, oh, that looks easy to get out, very complicated surgery and they bleed like hell, and so be careful.

So if you see this, this is a very dangerous tumour. Why? Because it's lost its pigment.

You can see it's going grey, and that means that it's undifferentiated, it's very dangerous. But here you see the whole back of the eye is filled with melanoma and yet there's nothing on the outside at all. Here you see the two eyes of the same.

Horse he's got a little melanoma here, a little nevus here, but this huge melanoma here, bound to affect vision to some extent, bound to do so. But is it worth interfering or not? In this case, we just opted to leave it.

We removed this one and we cauterised this just in case. But we left the horse after that and these had stayed the same probably for 9 or 10 years, and didn't alter, and I don't know what happened to the horse afterwards. they can occupy the whole front part of the eye, of course, in which case the horse is blind in the eye.

So, but you can diagnose that by ultrasound and of course, ultrasound is very important. Management, benign neglect, symetidine doesn't work, so don't bother with that. It never worked from the start and, and it should not surprise us because it is totally inappropriate in my view.

Surgical excision is the Treatment of choice. Remember that this is difficult inside the eye, but you may want to do cryosurgery or cisplatin or carboplatin, or now mitomycin C polymer and we're injecting these lesions in the eyelid to get them small so that the surgery is more limited. Whether it resolves them or not remains to be seen still very early in our development of this process.

It's a brand new method. So lymphoma, lymphoma occurs in the conjunctiva as well. As we said, there are naturally occurring lymphocyte, nodules or, or focuss within the conjunctiva.

These occur naturally, but they can become more severe. So here you see one on the limbus here and here, dorsal limbus, here's another one here, and here you see some in the lower eyelid. Just these are Now, our lymphoma lesions.

Here's that one we showed you before. And of course, if you see this one going to this, it's not good news. So here you see the the lymph nodes are generally enlarged, not the ipsilateral ones, but all of them.

That means it's part of a much wider issue. Here's an orbital lymphoma, single orbital lymphoma. The horse was completely normal in other respects.

What to do? Well, if you remove the eye, you've lost the visual eye. On the other hand, how do you get at the tumour because it's clearly having a consequence, as you can see from the edoema here.

So it's pushing the eye outwards, it's distorting the and distorting the, the lymphatic flow, so giving you conjunctival edoema and chemosis. And so what is your decision? And I think that's a personal decision for every individual clinician.

There are different forms with different prognoses, of course. So you see this is a conjunctival, one that's penetrated into the cornea. Again, this is a picture sent to me by David Wilkie, and I'm grateful to him for that help.

He has a focal lymphoma. He has a lymphoma in the orbit, which pushed the eye out to some extent, but mostly took the line of least resistance and pushed up into the supraorbital fossa. Important to remember that most localised forms can be removed effectively by one means or another, even if you have to sacrifice the eye.

The question is, is that the right thing to do? And then again, it's a personal decision that you have to make. So if you look at them, lymphoma, you can see, I mean, the pathologist will look for all this stuff, you know, dividing cells, all sorts of things, atypical nuclei like you see here.

And dividing cells like you see here. So these are very dangerous tumour full of nuclear cells lymphoma. Here's another one.

Actually, this was an interesting one because it, it just looked like a sarcoid because there were changes in the skin overlying it. But that was simply because the bulging of the The tumour was causing atrophy of the skin, so it's quite difficult. Then when we look closely, of course we could see another one in the upper eyelid.

So the question is, is it a sarcoid? Is it a melanoma even in a non-gray horse, and is it a mast cell tumour or is it a lymphoma? Because those are the tumour types that are most common.

Lymphoma, intraocular lymphoma like this very difficult of course, and there's nothing to do about them. Palpibral conjunctival forms, well, they're mostly localised, but, but may be part of a generalised syndrome as we showed you before. So here you see some of those again, kind of things that we see where there is a lymphoma.

Orbital lymphoma, where there's tumour inside the orbit, they're generally presented with edoema, conjunctival edoema, and bulging of the conjunctiva, so you can see them here. It's quite difficult to diagnose these, but you shouldn't be frightened of taking samples from these if you can, and, and getting a diagnosis because it does matter in some more cases. Here's a case.

This is the case we showed you earlier on with its lymph node enlargement. So if you see this and you've got this, well, then you can take a biopsy. Don't biopsy this.

There's no point. Biopsy the lymph node, just make a little skin incision over the lymph node and then push your biopsy, punch into it and take a piece of the lymph node. And the pathologist will no doubt delight in telling you that the horse has very marked lymphoma dash either usually, a B cell.

Lympho T cell rich B cell lymphoma, and sometimes T-cell lymphoma as well, that's much more serious, of course. So here you see the kind of thing that they get. This is the, the periocular tissue from that same horse, very proliferative with mononucleus.

Cells, but of course the submandibular lymph node confirmed the diagnosis. So it's a very carry touristic appearance in the lymph node. You've got lots of these very abnormal cells and so on and so forth within there.

I'm not a pathologist, but I enjoy looking. So, so don't forget to examine the horse. It's usually a horse attached to the, to the lymphoma or to the other tumour, come to that.

So if the horse has got pale mucous membranes, of course, it has a different implication. If there's lots of other bumps and lumps on it that are consistent with lymphoma, well, then, of course, you've got to be very careful. The prognosis and early biopsy is essential, but usually these are, you know, for localised forms your prognosis is reasonable, but for the prognosis for all other forms is pretty close to hopeless.

So be very careful of non-responsive UVIis. Examine the horse, be very careful when you do this. Looking at this blood sample here, you can see that even just a simple hematocrit shows the massive thickness of the white cells and of course when you look they are all lymphocytes, you see, so that tells you something.

It means it's leukemic's and therefore it's got lymphoma, you know, it's as simple as that. Mart cell tumours, unusual tumour again, and here you see an example of them. These are all mat cell tumours, as we explained before.

This was an interesting one because it was presented with a chronic long-standing. Corneal ulceration, very extensive corneal ulceration that never responded to anything. But if you look underneath, you see these little areas here.

This turns out to be a diffuse ma cell tumour. So very difficult, you know, genuine mat cell tumours. I'm not sure they exist, but nevertheless, maybe they associate with Habernemo or something or other else we don't know.

But surgical removal is the treatment of choice, of course, and they do respond very well. They don't have the same implication as mast cell tumours in other animals. You can inject them with diluted corticosteroids because they are osmotically very sensitive, so water injections, very cheap treatment, of course, can sometimes resolve some of them anyway.

Finally, undifferentiated myxoma, more often malignant, of course, and very invasive and very destructive. And of course, you don't need me to tell you that this is the case here. So these are both of the same tumour.

This was presented as a sarcoid, but actually it was clearly not. So you can see that this had this very destructive thing here and of course, a lot of bleeding and a lot of destruction within, within the orbit itself. So this was an undifferentiated myxoma, very aggressive tumour.

Oh, sorry. Hemangiosarcoma, it's sometimes seen very rare tumour inside here. You can see, but once they get going, they are really serious.

This is a very serious tumour, no matter what. So if you diagnose hemangiosarcoma, be extremely careful, and, make sure that the owner understands the implication of the disease. Lots of orbital masses, as we explained before, we haven't really got time to go through many of these, but, you know, there are lots of things that aren't neoplastic abscess, hydatid cyst.

These are much more common. Melanoma, reasonably common lymphoma, sometimes extraadrenal paraganglioma, you might see one or two in your life. Just be careful, scan them.

Send them to a specialist, get them away, get them looked at. Laryal gland, carcinoma, I've seen 3 in my life of these, only, and that's not very many in the global scheme of things. Extensions from the sinus, much more common, of course, sinus adenocarcinoma, commoner squamous cell carcinoma, commoner than most of the other types of orbital tumours.

Diagnosis, examine the horse, you know, just examine the horse. Remember to put a scope up the nasal cavity, you know, X-ray them, put a scope inside the sinus if you want, do all sorts of things in order to diagnose the problem. But of course, you've got an MRI and a scanner, you can do a lot of information.

Be careful, you know, people want to take out the eye here and then the horse bleeds like hell. They bleed and bleed and bleed and bleed, and it's very difficult to stop them, and they do stop sometimes, but mostly they're just such destructive tumours that I'm uncomfortable with dealing with this. Just be careful.

They can be symptom-free, of course, in a, in a lot of cases, but, be, can be very compromising or very painful or both. The meepithelioma we discussed before, usually young onset. They bleed like hell if you touch them, if you interfere with them.

This was the horse and before general anaesthesia, on general anaesthesia, going to the ground, just split it open and bled like hell everywhere. Of course, it's hardly surprising, it's a very difficult tumour to deal with. Here's the tumour that you see on ultrasound.

Diagnosed, diagnosed by immunohistochemistry using a panel here. you know, you can use this kind of thing. This is a pathology job, not ours.

There's no treatment, prognosis for the eye is nil. Early nucleation sometimes cures them. David Wilkie published a nice series of 12 where there was some effort at this, and, we were able to resolve the issue, in a few cases, but mostly by the time you see them, they're bad.

Differential diagnosis, of course, those same things we spoke about before. Time is critical, so you got to detect all these tumours early. You know, the important thing is don't remove a non-painful functional exothalmic eye unless you can definitively make a diagnosis.

it's important to do that, I think. Remember, finally, if you know the cells that are involved, you know, the tumours that can occur there. Some tumours are more common than others, but any tumour can occur.

The location and behaviour are important, and we need evidence, you know, I, I, I appeal for evidence. So if you have these cases, come on, please reach us, you know, let us know what it is and, and we'll, and we'll work away from there. Together to try to get information and get balanced evidence on what to do with them for the better.

So just to thank Dennis Brooks for his amazing, encouragement and support with my study of, of, periocular tumours. And, keep your eyes open, and, be careful with, ocular tumours. Thank you very much for your attention.