Video of The brain is simply an extension of the retina! Blindness due to optic nerve and brain disease

So, hello, everyone, and welcome to this lecture about blindness due to optic nerve and brain disease. Actually, if you've been following me, I am in the middle of, I guess you'd call it a marathon of lectures concerning blindness. We started Nearly a year ago, talking about the applied anatomy of the retina, we moved on to ophthalmic exam, including examining the blind patient.

Then earlier this year, we spoke about acute blindness in dogs. Today, we shall be talking about optic nerve and brain. Diseases causing blindness, and we have two more lectures coming up, where we'll be talking about blindness in cats and inherited retinal diseases causing blindness in dogs.

All the previous lectures are available on the webinar vet website if you have subscribe to it. And I'm sorry that once again, due to COVID-19, this is a recorded lecture, rather than a live presentation, and I take the opportunity to wish you and your family best of health in these difficult times. I'd really like for us to go back to live lectures.

Right. So today, as I said, we'll be talking about blindness due to optic nerve and brain diseases. Diseases of the optic nerve will include optic neuritis, optic nerve tumour, and other diseases of the orbit, and then we'll move from the optic nerve onto the optic chiasm and beyond.

Into the brain. By the way, this vest that the call is wearing is not just a gimmick. Actually, it's a very good and useful way to letting people know that the dog is blind.

As you know, blind dogs can be easily startled and scared because they don't see people approaching them. Or reaching out to pet them, and they may get scared and bite back. So, to avoid that, this is something you can recommend to your clients to buy on the internet and a very useful way, for people to know that this dog is blind and should be approached carefully.

So, let's start by talking, as I said, about diseases of the optic nerve and we'll start with optic neuritis. And by the way, here is a very good review of my colleague, Barbara Arnell from Vienna, Austria, a bit on the old side, 2008, but certainly an oldie but goodie, a good review of the topic if you wanna read about it. So what causes optic neuritis?

I guess that when we think of optic neuritis about the common causes of optic neuritis, we think about infectious causes, we think about meningitis, especially GME. And actually, as I'll show you today, idiopathic is probably the most common cause of optic neuritis. But as I said, the first item on my list as a common cause of optic neuritis is infectious diseases, although maybe I should say a reportedly common cause of optic neuritis, is infectious.

Diseases. If you go to textbooks, you will find long lists of infectious agents that can cause optic neuritis. Here is the list for dogs, you see, viral diseases, especially distemper, You'll see toxoplasma, parasites, fungal agents, a shorter list in cats, but again, viral diseases, toxoplasmosis, fungal diseases are common in these species, and here are the lists for horses and for cattle.

However, as someone who's actually written the chapter on neurophthalmology in Gillet's veterinary ophthalmology, I can tell you that one of the great advantages of writing textbooks is that you have no reviewer. And no one is actually reviewing what you're publishing and even in veterinary phthalmology, which is the holy of holies of our profession, you can write actually anything you believe to be true. But if you go and dig a little deeper into the literature and look for confirmed cases of optic neuritis, you discover that the list is actually much shorter, something that really startled me when I started digging into the literature.

So, here is a list of confirmed causes of optic neuritis, and as I said earlier, GME rules the list. You can see it as a very, as a common cause of optic neuritis, and we'll talk about GME later, but even though you see it quite often in this table, you see that the numbers are rather low, and often it is just suspected GME as you see here, an abstract, emitting abstract actually from Mike Davidson in 2002, cause it's a non, reviewed publication, it's in grey, rather than in red. .

But if you look for the list of infectious causes in this table, you see that they are even fewer in number. Montgomery had a report of 20 cases of optic neuritis. As you can see, out of the 23 were due to GME.

4 more had confirmed infectious agents identified and the rest were actually idiopathic or non-diagnosed. Martaleva from Barcelona looked at 46 cases of Erlichiaannis, and out of the 46, only 1 case actually had optic neuritis. The rest are all case reports of one single case of infectious optic neuritis.

An impressive, report is this one by Nikki armour, who had 11 patients with optic neuritis. She did serology for 9 infectious agents on each of the 1. Cases, so she ran a total of 99 serology panels.

Just one of the 99 came back positive for Rickettsia. So really, when you dig down in the numbers, infectious agents are actually not a very common cause of optic neuritis. Going back to this meeting abstract by Mike Davidson, which really represented a large study of optic neuritis cases, 50 cases.

We waited a very long time for Mike from the North Carolina State University to actually publish his paper, and eventually, it came out in 2017, by which time his caseload grew to 96 cases. So what were the causes of optic neuritis in these 96 patients? As I said earlier, GME is a very common cause.

There was also a fair number of neoplasia and cellulitis cases and we'll be discussing GME neoplasia and orbital cellulitis, but as I said, Confirmed infectious causes were actually very low number, 6 out of 96, and the majority of cases, close to 50% of the cases were actually idiopathic cases of of optic neuritis. So, who is your typical optic neuritis patient? As you can see, we're talking about middle aged dogs.

Half of them are small breed, but there is no genetic predisposition, and half of them are female dogs, so no sex predisposition either. Half of the patients had additional neurological signs. We'll be discussing them in a few minutes.

And as you can see, a fair number of them are actually unilateral, optic neuritis definitely is not a bilateral, disease. What were they presenting signs? We're talking about optic varieties, so obviously, all of them had either menace and or PLR deficits and as you can see, actually, nearly all dogs had deficits both in the menace response and the PLR test.

And many of them presented with edoema or detachment of the retina around the optic nerve. There was haemorrhage on the optic nerve and on the optic disc and punctate linear lesions around which you'll see in a minute. Maybe you can see some of them actually here.

Here are a few more pictures of optic neuritis cases and really, the distinguishing sign is the blurred edges of the optic disc. Here is a picture of a normal optic disc and you can see how sharp and well defined the margins are, and you can see how blurry they are, and that's because of the inflammation. The optic nerve head is inflamed, edematous, and that's why it is so blurry.

Here are the linear lesions that I mentioned in the previous slide, and another sign that you'll sometimes see is if you look closely here, you'll see that, and follow this blood vessel, you'll see it's actually climbing onto the surface of the disc. That's because when the optic disc is inflamed or swollen, and these blood vessels really have to Step up onto the surface of the disc, if you will. Note that you don't see this elevation of the blood vessels in this picture here where it makes its way straight onto the surface of the disc.

And again, another blurry optic nerve head with some haemorrhage on the surface of the disc. So when presented with such a patient, what diagnostic steps will you take? First, you'd obviously want to complete your physical, ophthalmic, and neurological exam, even though I said that if only a few cases are infectious, the patient may still have GME, so yes, you would want to complete a physical ophthalmic and neurological exam.

You would take a complete blood count and as in in biochemistry, and as indicated, you may wish to run serology for infectious agents. And if indicated based on all of these examinations, CSF analysis, cytology, advanced imaging, as we'll be talking about, and if you have a referral centre, they may run what's called fluorine and geography whereby you Inject fluorescine intravenously and watch it make its way onto the retinal blood vessels and onto the optic nervehead and you see how the optic nervehead lights up like a Christmas tree cause there is so much Fusion there as a result of the inflammation and there is also leakage of the fluorine, as you can see here and here because of the inflammation taking place, those linear streaks that I mentioned earlier. A couple of more diagnostic tech techniques that are out there.

The first one is one that you can certainly buy for a general practise, and that is the chromatic PLR testing whereby you check for PLR stimulating the pupils both with red and blue light and without going too much into the underlying physiology, pupils in Optic neuritis patients will respond to the blue light, but will not respond to the red light. So that's a very quick and dirty but quite sensitive test to diagnose optic neuritis in your patients. Another test that you may have to refer to is electroretinography, to refer your patients to other veterinarians, I mean to say, is electroretinography whereby specialists can record the electrophysiological responses of the retina to flashes of light.

Here is a paper looking at 14. 40 cases, 120 dogs were blind due to retinal disease, and 20 of them were blind due to optic neuritis. And basically the conclusion of the paper is that an ERG recording is indicated to rule out neurological disease in such cases.

The ERG is normal in optic neuritis cause the ERG, as I said, records retinal responses and optic neuritis is an optic nerve disease. The ERG is flat in cases of retinal disease. So, a very useful technique, to confirm your diagnosis that the retina is normal and the cause of blindness is in the optic nerve.

How do we treat our patients, our optic neuritis patients. Well, if you are fortunate enough to find an underlying cause such as fungal disease or toxoplasmosis, obviously, you'd wanna treat that. But if you have an idiopathic case where you have not been able to diagnose a specific cause, then we usually, use immunosuppressive treatment, prednisolone, mycophenolate, azathioprine, etc.

And in general, I should say that the prognosis is regarded as, rather poor, although that has been recently challenged as I'll show you in a minute, but in the North Carolina State University by Mike Davidson, 72 of the 96 dogs had follow-up of 2 weeks or more and out of those 72, 50 remained blind, 12 regained partial vision, and 10 regained normal vision, but 3 of them relapsed and actually became blind again. So as you can see, a rather guarded prognosis and we're talking just about 14 days follow-up, you know, if they don't. Becomes blind, months later, it didn't show up here.

You could, we were talking about very poor prognosis. As I said, we recently had another paper on optic neuritiss come out, actually published in the United Kingdom, looking at 28 dogs with optic neuritis and Again, I'm talking about non-infectious optic neuritis. The 28 of the 28 dogs, which is 56 eyes, 48 eyes were blind.

There were additional neurological signs in these dogs, in 5 of these dogs. Two of them did not involve the visual system. 29% of the cases of optic neuritis were due to retro retrobar disease, so the fundus looked normal.

We did not see the optic nerve had abnormalities that I showed you earlier. MRI was diagnostic in 67% of the cases. It demonstrated enlarged optic nerve heads and contrast enhancement, and the CSF was diagnostic in 88% of the cases.

This case, no, no chromatic PLR was used, but as you can see, ERG was used in more than half the patients to confirm the diagnosis. All of the dogs were treated with prednisolone, 1/3 of them only with prednisolone and 2/3 with additional drugs as you can see here, azathioprine, cytosine, and cyclosporin as additional drugs, and you can see that actually, the number of dogs, that regained vision was much better, 2/3 of them regained vision. Many of them with, and the duration for which they were treated and the And the outcome, whether they regained vision or not depended on how fast they were referred.

So if they were referred quickly, vision was regained quickly and if they were referred rather late, then the vision was not regained in these cases. Right. So moving on to our next cause of optic nerve disease causing blindness.

We're talking about optic nerve tumours and about other orbital disease. So really orbital disease I should say, whether it is tumours or other causes. So when you have an orbital disease or retrovulbar disease, There are some signs that are common to all rebel-barre disease regardless of the cause.

A retrobulbar disease is often a unilateral disease. It causes exopthalamus cause there is a retrobulbar mass, so there is a mass behind the eye pushing it forward. It will also push forward the third eyelid, so we'll get 3rd eyelid elevation.

It disrupts the circulation in the orbits, you'll get lots of swelling, periocular swelling in orbital swelling. Because of the mass, there will be resistance to retropulsion, which is what we are doing here. You place your fingers on the eyelids and you press on the eye, you press on the globe.

What we're doing here is we're not measuring intraocular pressure. You cannot measure intraocular pressure with your fingers. You can do lots of things with your fingers, but for measuring intraocular pressure, you actually need a thermometer.

What we're doing here is Pressing on the eye and seeing whether we are, we are able to push it back into the orbit or whether there is a mass behind the eye that's resisting this pushing and will not let us push the eye back into the orbit. So that's a very important sign of a retro ballbar or orbital disease. And then there could be signs of systemic or neurological disease depending on the cause, depending on metastasis or spread to the brain or to the body.

Other cranial nerves may be affected besides cranial nerve number 2. Obviously involvement of cranial nerve number 2 would cause blindness, but you may have involvement of cranial nerves 35, and 7, which are all have ophthalmic implications. As we know, the two main retrovular diseases are tumours and inflammation of the optic nerve.

And if this was actually a live question, I think this would be a time to ask a poll question and ask you which do you think is more common, a more common cause of orbital disease, inflammation, abscesses, or tumours, and If you look at this series of papers, you would see that actually tumours are a far more common cause of optic nerve or retrovular disease as compared to inflammation. Here is a series of 3 papers comparing these two diseases and we shall be examining and going through these papers. So, the first paper here looked at dogs and cats with tumour and inflammation, and again, you can see that the tumour is approximately 3 times more common than the inflammation.

And this study, as you can see here, try to try to identify the, to differentiate between the two diseases using CT changes, and they use CT to examine all of the tissues in and around the orbit. Looking at subcutaneous tissue, looking at the eye, at the optic nervehead, the fat, salivary glands, extraocular muscles, lymph nodes, etc. Etc.

And actually, you can see the changes in all of these tissues were not helpful in differentiating between orbital tumours or orbital inflammation. There were actually only 4 anatomical sites that were predictive of neoplasia or inflammation, changes in the orbital bones and in the interior segment of the eye were more predictive of neoplasia and As you can see here, changes in the skin and the fat were more predictive of inflammation, but the odds ratio, as you can see here, were rather low, meaning that the actual differences or the actual sensitivity of CT in determining whether it's inflammation or neoplasia based on changes in these four tissues were not very predictive. Another imaging studies looking this and comparing ultrasound and CT in unilateral orbital diseases in dogs, and again, you can see that neoplasia is much more frequent than the non neoplastic disease.

And basically, there was no difference between ultrasound. And CT except obviously in showing extraorbital extension. So if the tumour was extending into the bone and into the brain, the CT would show it, the ultrasound wouldn't.

Basically, both modalities demonstrated that neoplastic diseases are More focal, more homogeneous, and more hypoechoic with clearly delineated margins, and they were associated with more globe indentation as the tumour is pressing on the globe, more bony involvement and as I said, more extension and more mineralization. But obviously, other than imaging to try and differentiate between a retro bulbar mass that is inflammatory or a retrobar mass that is neoplastic, you have to do. Ultrasound guided fine needle aspiration, as you can see here, get your cytological sample and see whether you are looking at a mass that is a tumour or a mass that is an abscess.

So, let's begin by talking about an abscess, even though I said it is the less common of the two presentations. I showed you earlier a list of signs that are common to both an abscess and a tumour, but there are some unique signs to each of the diseases. Unique signs of retrobulbar abscess is that the onset is very Very acute.

You get acute exothalus, third eyelid elevation and swelling, as you would expect in most cases of abscesses. You'd get pain on opening the mouth, and that's because when the patient opens its mouth, the epicondyle of the mandibula goes up and presses on the abscess, very painful, so actually the dog refuse to open its mouth, it would refuse to eat. And when you finally manage to open the mouth often after sedation, then you may see a swelling or a fistula in the oral mucosa behind the last upper molar tooth that is usually where you will find the the orbital abscess.

You may feel that I'm slightly drifting away from my topic as I'm starting to talk about retro bulbar abscess, and some of you may be suspecting that I am forgetting that I'm here to talk about causes of blindness, non-ocular causes of blindness. So, here is a study again out of the United Kingdom, showing why retro bulbar abscesses are, in my list of different. Here is a study looking at 41 dogs with a retro bulbar abscess, and you can see that 17 of the 41 were actually blind, which is why I am talking about orbital diseases causing blindness.

Of those 17, 5 were actually blind due to optic nerve involvement, 3, due to chorea retinitis, retinal detachment, and glaucoma. Because we have an inflammation in the orbit, as I implied earlier, other cranial nerves may be involved, and therefore, 3 of the dogs also presented with facial nerve paralysis and 5 dogs with internal ophthalmoplegia, meaning that there was involvement of a cranial nerve 3 and innervation of the iris sphincter. There were also additional opthalmic signs.

There was interior uveitis, corneal ulceration, because of the thalamus, cornea was exposed and became ulcerated. And three cases of cherry eye, again, as I mentioned, there is pressure, on the On the 3rd eyelid in cases of retrovular disease. What were the causes of What were the causes of the retro bulbar abscess in these 41 dogs?

Well, once again, half of them were idiopathic, just like optic neuritis. The cause often couldn't be, determined. In those cases where the cause could be determined, there was a bit of a surprise.

We usually associate a retroboulbar abscess with dental disease, but as you can see, actually, dental Disease was the 2nd most common cause of retroboulbar abscess. Majority of them were caused by a stick injury. The dog is chewing on a stick and it goes up through the soft palate into the retro bulbar space, dental disease, other foreign bodies making their way to the retro bulbar space or involvement of a salivary glands.

Taking cyto cytology was taken in 17 patients and in 11 of them neutrophilic inflammation could be identified. Cultural and sensitivity was collected in from 21 patients and was positive in 14 cases, most of them aerobic species. Note that a majority of patients were either Labrador or spaniel breeds, maybe because they are active outdoors and like to chew on those sticks that are shown to be a common cause of the retro bulbar disease or retrobulbar abscess.

How do we treat these patients? Well, You must anaesthetize the patient and you must intubate the patient, because soon the oral cavity will fill with lots of inflammatory debris. You see that we not only intubate the patients, we also pack lots of gauze around it, endotracheal tube to make sure that none of the inflammatory debris makes its way down the trachea.

Then if you have a fist, a fistula, then you can drain it, as I'll show you in a minute. If you can't see a fistula or see a swelling, just make an incision here behind the last molar tooth and as I said, create a draining tract using a closed hemostat and I emphasise the word closed. You go on in with a closed hemostat, open it once in order to break.

Drain the abscess, pull it out when it's open, close it in the oral cavity, and again, go in closed, open one, pull it out, open, close, and go in. What I don't want you doing is going into the retro bulbar space and start closing and opening, closing and opening the hemostat in order to create the draining track cause I promised you that sooner or later, you will clump on the optic nerve and the dog will wake up blind. As you saw earlier, you can, collect the fluid, and submitive culture and sensitivity or cytology.

I often don't do it cause by the time the, I get the results come back, the dog has recovered, these patients recover very quickly. I just flush the tract with say. Antibiotics, place it on systemic antibiotics and give it soft food for a few days.

And really, it's a very satisfying procedure cause a very sick and anorectic dog came into your clinic and within 2 days, it's back to normal. So, this is one, the, the disease, orbital disease, causing blindness, retrobulbar abscesses. The other, as I said, is a retro bulbar tumour.

Actually, it's the more common of the two and just like retro bulbar abscess, retro bulbar tumours also have The unique signs. Unlike the abscesses that were acute, these are slowly progressive, as are most tumours. They are non-painful because there is no abscess for the epicondyle to press on.

Naturally, they are seen in older patients, though not always, as I'll show you in a minute. And As the tumour grows, it may cause, you may see signs of local extension. You see here this retrobulbar tumour causing deviation of the globe.

It may cause nasal discharge as it extends into the nasal sinuses. It may Cause CNS signs as it extends into the brain. And as I said earlier, you may see it ophthalmoscopically as it presses on the globe from behind and causes this indentation that we are showing in this patient.

These patients can also present with a, additional signs, besides, the signs of, presented. So, obviously you're talking about a tumour in the orbit between the eye and the brain, so you may get neurological involvement of these 29 dogs from the paper. Is presented earlier, 7 were blind and 3 more had additional neurological signs.

There was extension into the nasal sinuses, to the lymph nodes. There was absothalus, obviously, there was decreased retropulsion that I mentioned earlier and in this study, half of the dogs presented with lethargy, pain, and Elevated 3rd eyelid as the tumour presses on the 3rd eyelid. And in fact, case in point, this is a dog I had in the clinic just a few months ago, the percentage with A 2-week history of elevated third eyelid.

This is shaved. That's why that, it may look abnormal, abnormal, but you can see really a very normal looking eye, a very mild sign of elevated third eyelid. This is what the CT of the patient looked like.

You can see the massive extension into the brain and into the sinuses. It's really amazing to see the amount of damage here to the bone, and this was actually the presenting complaint of the owner. So, if we're talking about retro retro bulbar tumours, what tumours are we talking about?

What are the common tumours? Here are two studies and As you can see in this one, carcinoma, sarcoma, and lymphoma were the three more common tumours. And in this study by Mickey armour, we are talking again about carcinoma being the most common one and sarcoma meningioma being the other two common tumours.

Here is a breakdown between dogs and cats in this study by Mickey armour. So again, you can see that a carcinoma, sarcoma, and meningioma are common tumours in dogs, and in cats, you will see carcinoma, sarcoma, and lymphoma being common tumours in these patients. Here is another paper that came out, as you can see just last year, and added another 112 cases of orbital neoplasia to the literature.

The median age of these 112 patients was 9, even though the range of ages was 6 months to 16 years. So yes, you can get retrobullbar neoplasia at a very young age. As you can see, a majority of dogs were Labradors and Labrador crosses, and golden retrievers and boxers were also overrepresented.

What kind of tumours? Again, we're talking about lots of epithelial tumours, lots of carcinomas. We are talking about lots of mesenchymal tumours, lots of sarcomas, some round cell tumours, melanoma and lymphoma, and a minority were neural origin, meningioma, and oligodendriglioma.

Interesting note about this paper is, as you can see here, they used actually two. Diagnostic methods, cytology and histopathology to reach a diagnosis. So fine needle aspiration was available from 47 dogs and histopathology obtained with punch biopsy or guided cord needle biopsy, as you can see here, was available for 95 dogs.

You can see it inserted here in a diagram and in an ultrasound to take a histopathological sample. Interesting to note that 32%, 1/3 of the FNA cytology were overturned or non-diagnostic. Only 13% of the 95 dogs, for which histopathology was available.

Only 13% was it the diagnosis overturned or non-diagnostic. So yes, the image guided core needle biopsy is far more diagnostic, something we really didn't know, but, you may wish to consider using this technique. So we're talking about carcinoma and lymphoma, and meningioma, and all these orbital tumours.

Where do they actually come from? As you can see, if you've diagnosed carcinoma, they originate mostly in the nasal cavity, some of them from the lacrimal gland, the thirdilid gland, etc. Etc.

And really just a minority of Them are originating in the orbit. Lymphoma and sarcoma are mostly orbital and meningioma, as you would expect, a majority are intracranial, which brings us to our next and final topic here, and that is diseases of the opticaya. And post-chiasal disease.

So, we are moving into talking about brain tumours, about GME and a brief word about infectious encephalopathy. But as I said, since we ended up talking about orbital tumours, we'll continue with orbital brains, . Orbital, so into, we, we're moving into brain tumours, sorry.

And actually, surprisingly enough, brain tumours are associated with acute blindness. Here is Here are two reports, one by Sirua from Barcelona, in which acute blindness was caused by 2 cases of meningioma, 1 pituitary tumour, and 2 extensions of nasal tumour. The second case again out of North Carolina State University, 7 cases of acute blindness, due to tumours.

4 of these were suspected to be pituitary tumours, as you can see here, due to, based on either MRI or endocrinological, findings. And Actually, we do tend to associate pituitary tumours with acute blindness cause we think that they press on the chiasm, but as you can see, there was really just one pituitary tumour in this study that pressed on the chiasm, and the reason for that is The reason for that, I can only quote the la junta, probably the most respected neuroanatomist in the world, who says that most pituitary neoplasms grow dorsally into the hypothalamus and usually do not involve cranial nerve 3 and the dorsal growth also usually spurs the optic nerve and the chiasm. So really a bit of a myth here.

Maybe it's a second myth I'm busting. Earlier, I busted the myth about dental disease, meaning common cause of retro bulbar abscess. So, another myth busted here, that pituitary tumours will cause acute blindness.

It's also supported by this paper here from the University of California Davis, looking at 157 cases. Of pituitary tumours, neurological signs were actually found just in 73 dogs and blindness due to compression of the opticiam just in 3 dogs. So really not a very a very cause of acute blindness, these pituitary tumours supposedly pressing on the opticciain.

If I'm talking about acute blindness and the opticism, I must also mention this paper again out of the United Kingdom, about nucleation in cats as a cause of acute blindness. The reason for that is that the retro. Bulbar section of the optic nerve, the part of the optic nerve between the globe and the between the optic chiasm is rather long in dogs, but it is very, very short in cats.

And what happens sometimes when people in nucleate cats is they reach behind. The globe, that's to be nucleated with their hemostat to clamp on the optic nerve and prevent haemorrhage. And because the retro bulbar optic nerve is very short, they sometimes end up clumping on the optic chiasm and that causes Damage to the other optic nerve and the cat wakes up blind.

One eye has been nucleated and the other eye, which was fine just a few minutes ago, is now blind due to damage to the optic nerve and the opticiam. So please be careful when Please be careful when in creating cats. As I said, sometimes, brain tumours will cause acute blindness.

I showed you two papers, but usually it is more of a slowly progressive process. It is due to tumours. In the a to cerebral or the encephalon tumours, not brain stem tumours.

As I said, it is slowly progressive and there'll be lots of other neurological signs such as seizures, behaviours, changes, circling and head pressing. What are the patients, they, we're talking about middle aged dogs and cats. Meningioma is one common cause of brain tumours leading to blindness, especially in golden retrievers, and glioma would be the second common tumour, which is found mostly in uhchicephalic breeds and in the boxers, and here you can see a case of canine brain glioma.

How do we diagnose and treat these dogs with the brain tumours? Well, in addition to the neurological signs that I showed you in the previous slides, there may be neck pain, there may be placement deficits, and if we have all of these signs, we will take the dog to advanced imaging MRI is preferred in these cases of suspected tumours. Obviously, you will also be considering CSF which is often abnormal, but the findings are rather non-specific.

Treatment, you may consider surgery or radiation depending on the species, on the tumour type. The median survival time following treatment is, half a year to 3.5 years.

Without treatment, it is less, and chemotherapy is generally ineffective. Here you can see a series of photos taken. And in a case of canine pituitary tumour following radiotherapy and you can see how the tumour slowly reduces in size.

So yes, it may be useful, but usually no more than 3.5 years. So still with brain, sorry, we covered brain tumours.

The other disease I want to cover is GME granulomatose meningoencephalitis. What is GME? Actually, the underlying cause of the disease remains unclear, but we do suspect an autoimmune inflammation, of delayed type hypersensitivity.

The autoimmune reaction involves inflammatory cells of unknown origin, that proliferate. In the CNS or migrate to the CNS and this cause this inflammatory response that presents as perivascular coughing or granulomas or a meningitis, that's because the perivascular cuffs, I would often would often lead to the formation of granulomas that mimic, space occupying lesions. In general, the lesions are of varying size and severity can be found throughout the brain and the cervical spine and usually affect the white matter to greater extent than the grey matter.

There are 3 classical forms of GME that are described in the literature. The focal and the metallic focal forms present with, as I said, signs consistent with the space occupying masses and the signs will really. Depend on the precise location of these masses and their number, if it's focal one granuloma or multifocal, multiple granulomas, this form of GME is characterised by slower onset and slower progression.

The patients usually will deteriorate over 3 to 6 months. The multifocal form will progress more rapidly. You can see here it's down to 6 weeks and has a more acute onset.

The form may present with a variety of clinical signs, but the localization will always show the multifocal neurological involvement. Then there is also an ocular form of GME. Which involves inflammation and granulomas in the optic nerve.

It leads to atrophy of the optic nerve and the optic nerve head, as you can see here, and may also cause anterior and posterioritis, retinal haemorrhage, and detachment. So lots of reasons for GME patients to become blind. How do we diagnose GME?

Well, CSF samples will reveal mononuclear pleocytosis and elevated protein, but that's non, specific. Really, the gold standard is CT that would show contrast enhanced regions. And CT guided biopsy of these masses is considered the gold standard.

MRI will show you the granulomas that you can see with these Xs marking the granulomas here with or without contrast. How do we treat these GME patients? Well, it's an inflammation, so we use corticosteroids at a rather high dose.

You can slowly try and taper it after 4 months, but actually, you are never able to stop, completely stop treatment. Cyclosporin has also been attempted, but really the long-term prognosis of this disease is poor. Sometimes vision may improve temporarily, but as you can see here, these dogs have a very poor survival rate.

And as we are running out of time, I'm afraid I don't have too much time to discuss infectious encephalopathy as a cause of blindness. So I'll just say that bacterial agents are very uncommon. Fungal disease, you should definitely consider Cryptococcus, but depending on what's prevalent in your area, other fungal agents may also cause encephalopathy.

Viral agents, obviously, if you are looking at a dog, then distemper would be at the top of your list, and the concurrent dry eye may be a sign that indeed you are looking at a case of distemper and if your patient is a cat, then FIP is the most common viral cause of encephalopathy, though you should consider rabies, FIV West Nile virus, and I viral agents and Looking at protozoa, I think everyone knows that Toxo and neospora are common protozoal agents of encephalopathy. So, this concludes this talk about optic nerve and brain disease as causes of blindness. As I said, we'll be continuing the series later this summer.

In the meantime, because this is a recorded lecture and I don't see you, I can't. Hear you. I have brought my own applause.

I thank you very much for your attention. I wish you a healthy, best of health to you and your family, and I hope to see you later this summer. Thank you very much.