So, hello, everyone, and welcome to today's webinar about ocular manifestations of systemic diseases. Now, obviously, it's impossible to cover all of the systemic diseases that have ocular manifestations in a one hour talk cause really the list of diseases is endless and therefore I decided that today I shall be concentrating on the non-infectious diseases and that's Because, I have covered lots of the ocular manifestations of the infectious diseases in previous webinars with webinar vet, so you can watch those recordings, just as a quick reminder, we've discussed UVITs back in January 2019. And you may recall this table here that shows us the causes of UVITs and Well, the print is small here, you can't really make out individual diseases, but what should impress you is really the length of the list.

Virtually any systemic disease may cause UVI. Some of them are metabolic or immune mediated, and we may touch on them today, but you can see that practically any infectious diseases, be it algae, bacteria. Protozoal fungal and viral disease can cause UVI and that's why I said in my talk, back in January 2019 that UVIis is really a clinical sign, not a diagnosis.

Once you determine that an animal has UVIis, then you need to ask yourself what caused it. The Diagnosis of UVIis is really only an indication for further workup to diagnose a systemic disease. If you are not watching the January 2019 recording, let me wrap it up for you in just one slide.

Patients will present with blue eye and Red eye and unfortunately, these signs are also seen in glaucoma, so sometimes it may be difficult to differentiate between the two diseases. We differentiate between them based on pupil size, which is fixed and dilated in glaucoma and meiotic in uveitis. Intraocular pressure is obviously.

Elevated in glaucoma and lowered in uveitis, the iris is more congested in uveitis and uveitis is also characterised by aqueous flare as inflammatory material leaks into the interior chamber and may sink to the bottom. This hypopion that you're sitting here. That you're seeing here.

And as I've just said, once you determined that the patient has UVITs, you look for a systemic cause. However, beware that 40 to 50% of the cases are idiopathic and despite extensive workup, you may not find the cause. And we do treat the primary cause if we found it, and the eye is treated symptomatically with anti-inflammatory drugs and with atropine.

Another manifestation of infectious diseases is blindness and mostly optic neuritis, and I refer you to these two talks that I gave and are available at the webinar vets archives. So as you can see, optic neuritis may be caused by a host of systemic infectious diseases listed here as well as GME which is also A systemic disease. So that was covered in the optic notoriety talk when we spoke about acute blindness.

And again, if you're not watching the recording, a one slide wrap up, when you're presented with a patient that has acute blindness and fixed dilated pupils, you really should consider for differential diagnosis, glaucoma. Retinal detachment, optic neuritis, and SARS, patients with retinal detachment and optic neuritis should be worked up for systemic disease. Here is a list of diseases for optic neuritis and retinal detachment, the list would be similar to what I showed you earlier as causes of UVis.

In glaucoma, please treat the unaffected eye if you suspect that the disease is primary. ERG is used to distinguish between SARS and optic neuritis. SARS, the ERG will be extinguished because it's retinal degeneration and optic neuritis, the ERG will reflect normal retinal activity.

And finally, despite what some people may claim, there is no efficacious treatment for SARS. So this is a one slide summary of my talks about. Acute blindness, which allows me to move on to today's topic, as I said, ocular manifestations of the non-infectious diseases, we cover at great length endocrinological diseases, diabetes, Cushing's, and hypothyroidism.

We'll talk about some odds and ends. Mainly dermatological manifestation manifestations of dermatological diseases manifested in the eyelids and finally, we shall wrap it up with differential diagnosis of the different lesions and what are the systemic diseases that you should consider when presented with each and every lesion. So, starting things off with diabetes mellitus, diabetes really has lots of Ocular manifestations that are listed here.

Cataracts are the most common manifestation, the cataract that you're seeing here, but we are also seeing ocular surface diseases, poor corneal healing. Lienia retinalis and lipid-laden aqueous diabetic retinopathy, and don't worry if you're not familiar with these terms, we are going to cover all of these items one by one. The only one I'm not going to cover is UVIT because as I said, that is covered in my talk from January 2019.

So, as it says here, the most common manifestation of a diabetes meditu is cataracts and really diabetes medus should be suspected in every case where you are seeing vacuolar cataracts. In the periphery of the lens, such as you are seeing here, obviously you must dilate the pupil in order to catch this cause as I said, they are in the periphery and these vacuoles. Caused by entry of fluid into the lens are really a very early sign of diabetic cataract.

You should also suspect that Bees mellitus whenever you have an incent cataract, such as the one that's shown here, when I say intubscent cataract, I mean a swollen cataract. Because of the fluid entering the lens, the lens really swells. It is much larger than it usually is.

It is much larger than your tip. Inherited cataract would be, you would see the iris pushed forward, the shallow interior chamber. You may see these so-called Mercedes signs that you're seeing here, which is really a fracture of the lens sutures, in fact, it can swell so much that the lens capsule will rupture and that could lead to a devastating lens induced uitis.

And finally, Another The thing that should clue you to the fact that you are looking at the diabetic cataract is that they are very quickly progressing. We see cataracts go from 0 to 100 in like 2 weeks, OK? In 2 weeks, they can go from a completely transparent lens to a fully mature cataract and a blind eye.

So that is another hint that you are looking at diabetic cataracts. Why do diabetic patients get cataracts? This is shown here in this diagram, which is the pathway of glucose metabolism in the lens and as you can see, two enzymes are involved in This metabolism, hexoynase and aldose reductase, and under normal conditions, this is the ratio of the glucose that is shunted into the hexoynas pathway and into the aldose reductas pathway.

OK. Most of it, as you can see, is converted by hexokinase into fructose. The problem is that when we have diabetes, the hexokine pathway becomes saturated and the excess glucose is diverted to the aldosta pathway resulting in a higher concentration of sorbitol.

Sorbitol is a large molecule. It cannot. Leak out of the lens.

It stays in the lens and therefore you get a hyper osmolarity of the lens, and when the lens has hyper osmolarity, you get fluid, you get aqueous humour entering the lens, causing those vacuoles, causing the swelling, causing the rapidly progressing cataract that I described previously. You may be asking yourself, why am I showing you this diagram, which is something you may have learned in school and forgot. Actually, this diagram is an explanation for why we see, we do not see, sorry, diabetic cataracts in cats.

And the reason we don't Because obviously cats do get diabetes, but we don't see diabetic cataracts in these patients. And the reason is that hexodos reductase, the enzyme responsible for the production of sorbitol, becomes inactive in cats around 4 years of age. As you know, diabetes is a disease of elderly cats, and by the time they develop the disease, they don't have the aldos reductase that is responsible for diabetic cataracts, so they are free of this complication.

Unfortunately, the enzyme is very active in diabetic dogs and most of them, as I said, will develop diabetic cataracts, half of them within 6 months. 3/4 of them by 12 months, 80% by 16 months, all due to the aldose reductase enzyme. Which is why we were very hopeful when researchers in the United States developed kenostat, which is an aldos reductase inhibitor, delivered eye drops and it Because it inhibits the enzyme, it actually inhibits the development of diabetic cataracts due to hyperglycemia.

The drug even got FDA approval, which means it was really ready to be marketed, but it never was marketed and to this day it remains a mystery. As you can see, this paper is from 2019, so we're talking about recently. We're still waiting for that drug.

It would be wonderful, if it comes out. No one can understand the delay, but please be on the lookout for it. But until it comes out, you may ask yourself, can I prevent diabetic, cataracts by improving the diabetic control of my patients.

And this is a study that Yours truly has actually finished right now in cooperation with our internal medicine service and I'm presenting it as you can see here in about 1 month at the meeting of the American College of Veterinary Ophthalmologists. And what we did here was we took 10 dogs that have just been diagnosed with diabetes and their lens were still completely transparent. We put freestyle sensors on this, on these dogs.

I don't know if you're familiar with them, but these are sensors that take continuous, glucose readings and, after 2 weeks, we can download them to a computer and get continuous 2 weeks reading of glucose levels, and the owners showed up every 2 weeks, for An evaluation by internal medicine and an evaluation by yours truly checking for progression of cataracts. And the study lasted 6 months. We recruited, as I said, 10 dogs.

Cataract progression was slower than has been reported in the literature what I showed you earlier, . 50 to 70% expected in 6 months. We're not seeing that maybe because these patients are seeing an internal medicine specialist every two weeks.

So that suggests that yes, these frequent rechecks and the improved control will slow down the progression. And to answer this question, cataract progression is associated. With glucose variability, not with the levels of fructosamine or HbA1c, but with the variability, it's the fluctuations in the glucose levels that actually cause the diabetic cataract.

So you're getting a sneak preview of what I'll be presenting next month and then writing up as a paper. Since we are talking about cataracts, I should mention once again that I gave a talk about it in May 2019, available in the webinar vet archives, but one very, very important slide from that talk. In diabetic cataracts, so we do have secondary lens-induced UVIT just like we have it in every mature cataract.

This should be treated with an anti-inflammatory. Drug, obviously because the patient is diabetic, we should not be treating it with steroids. We shall be treating it with non-steroidal drugs.

However, the important message I want to get across time again and again is that there are no drugs that dissolve cataract or prevent their formation other than the kenostat that I mentioned that is not yet marketed. And that is very important and I'm emphasising. This point, because today, people go look for cheap, easy miracle solutions on the internet.

And if you diagnose their dog, their diabetic dog with cataract, they'll go and you offer them a $5000 surgery. Well, before agreeing to surgery, some of them will go to the internet and start searching for miracle drugs and, yeah, herbal treatment for cataracts, OK. Can see eye drops.

I love the name. OK. Can see can see eye drops safely reverse cataracts in dogs.

Wow, this is wonderful. Why should they do a $5000 surgery if I can get this for $100? The answer I give, owners who come to me with this question and the answer you should give is that cataract surgery is the most common surgery in people.

It's not the most common ophthalmic surgery. It's the most common surgery in people, period, OK? Millions and millions of people who have cataract surgery.

Every year, it's a problem that has huge economic impact on, health services, medical insurance companies, hospitals, etc. If there were drugs that could dissolve or reverse cataracts, People wouldn't be selling them on the internet for $100. They'd be selling the patent to Novartis for a billion dollars, and they would sit home waiting for a telephone call from the Nobel Prize committee.

OK? Cataract is a surgical case and don't let owners tell you otherwise. So, we've spoken at length about the most common manifestation of diabetes in our patients, but there are other manifestations.

Diabetes is also associated with ocular surface disease and that is due to several reasons. Number one, diabetic patients have lower tier production, a paper by England's very own David Williams from Cambridge. I'll be showing you that paper later.

Not only do they produce less tears, the tears also evaporate faster, so less tears, faster evaporation. They can get conjunctivitis cause of epithelial dysplasia in diabetes. You can see here the conjunctiva of a healthy patient and a diabetic patient.

And even if you are not a pathologist, you can tell the difference in the conjunctival epithelium between this patient and this patient, and these pinkish PAS positive cells that you were seeing here are the conjunctival goblet cells which are missing in the diabetic patients, the conjunctival, . Goblet cells are the cells responsible for producing using part of the tear film and that's why we get the decrease, the increased evaporation, the decreased tear film breakup time. And of all this wasn't enough.

Their tears also have higher glucose levels, which means that bacteria would like to settle there. So all of these factors predispose to ocular surface disease, conjunctivitis, dry eye, and corneal ulceration. But as if this wasn't enough, we have other complications leading to ocular surface disease.

We know that diabetes causes the neuropathy, diabetic neuropathy, and part of the diabetic neuropathy is manifested in the corneal trigeminal nerve. So these patients have decreased corneal sensitivity and that's important cause The patients cannot blink and therefore they can't . Wash away foreign bodies and they are unable to spread the tear film.

So again, if we go back to the previous slide, they produce less tears. The tears evaporate faster and with little tears are left, the dog is unable to really spread them on the cornea cause it is not blinking. So we've Got lots of problems here and another problem is because of loss of sensation, if the, if and when the dog develops corneal ulcers, the owners won't notice them because the dog has decreased corneal sensitivity sensitivity, it's not showing signs of pain.

So these dogs are really. May really present with recurrent corneal ulceration, ulcers that failed to heal or are not responsive to treatment and therefore you should really, really watch your diabetic patients very careful. For development of corneal ulcerations, especially in the bracket cephalic breeds that have decreased corneal sensitivity to begin with, and as if this all this wasn't enough, they also lose their endothelial cells and develop corneal edoema.

Unfortunately, we're not done with the ocular manifestations of systemic disease. We, patients may get lepemic uveitis. Lepemic uveitis, as the name implies, is uveitis caused by lipids in the anterior chamber and you can see here 3 degrees or 3 stages of the disease.

A bit of lipids, much more. And here is an eye that is totally, totally blinded by having so much lipids in the aquium or Here you can still barely make out the iris and the pupil. Here you can't see anything.

This is not a flare. This is not hypopion. If you've ruled it out, maybe you are.

Seeing lippemic UVIs. Here is a study from Cornell Vet School in New York at the United States, looking at 75 cases of lippemic UVITs. Not surprisingly, 95% of these dogs had hypertriglyceridemia, which leads to lepemic UVITs, and 72% of them were.

Due to diabetic mellitus, OK? Other diseases that are associated with hyperlipidemia such as Cushing's, hypothyroidism, and pancreatitis were diagnosed in each was diagnosed in less than 5% of the patients. Some of them had hyperlipidemia, but really when you are seeing panic UVIis, you need to think of diabetic meds.

Obviously, for, nearly half the patients had A dry eye, corneal ulceration, and cataracts, as I've just described, and many of them had undergone cataract surgery and that may have triggered the lippeic uveitis. Half of them developed it within a month of surgery because surgery does trigger uveitis. It breaks down the blood aqueous barrier and that allowed the lipids to leak into the anterior chamber.

In patients with hyperlipidemia, we, the presentation of lipids is not restricted to the interior chamber. We also see it in the retina, a phenomenon that we call pea retinalis. Here you can see that the blood flowing in the blood vessels is not of normal colour.

It is definitely more whitish or creamish and here you have it. Extreme case of lipemia retina is one great advantage of the eye and the retina is that in a non-invasive manner, you can look at blood vessels and you can see changes in the colour, in the consistency, etc. Etc.

Every other tissue, you'd have to cut it open to see the blood vessels, but here with an ophthalmoscope, we can see these changes. So we've said that diabetes causes cataracts, it causes ocular surface disease, dry eye conjunctivitis, ulcers that won't heal, lippeicubitis, lepemia retinalis. You'd think that we are done, but we are not done.

We still have one more manifestation, diabetic retinopathy. There is decreased blood flow in these patients due to increased viscosity. Sorry, I forgot the D here, sludging and aggregation of the red blood cells, lots of fibrino as you know, in these patients, and lots of histological changes in the blood vessels of these patients and the result is rettal haemorrhage.

It's not massive rectal haemorrhage like you'd see in a likia or systemic hypertension. It's more of a punctate haemorrhage as you can see here. Here and again another study out of Cornell University in New York looking at punctate retinal haemorrhage and the relationship to ocular and systemic disease.

83 dogs were studied, 50 of them had systemic disease, so it ties in nicely with the title of our talk, ocular manifestations of Systemic Disease, and as you can see, half of them were diabetic patients. OK. The rest were systemic hypertension, hypothyroidism, and chronic Renal disease which may have led to cystic hypertension, Cushing's multiple myeloma, and in 33, it was due to intraocular disease.

But again, diabetes rules the list of the differentials for these punctate haemorrhages. Obviously, they may be masked by the presence of diabetic cataracts, which is why we may see them only after we've Done cataract surgery. This is a study out of Virginia University, in the United States, and you can see that signs of diabetic retinopathy were found in 21% of dogs after cataract surgery, and they're hardly seen in the reference population.

I know we're all veterinarians, but since I'm talking about diabetic retinopathy, I must mention the human consequence of the disease cause I'm sure that you may, I'm sure that you have or may have relatives with diabetes and really, diabetic patients, human diabetic patients also develop Diabetic retinopathy, you can see 20 to 30% depending on where you are. And in humans, the bleeding into the retina is much more significant and massive than in our canine patients, thank God, and Actually, diabetic retinopathy is a leading cause of blindness in people, a leading cause of severe visual impairment. So really, if you have relatives with diabetes, they should be checked by an ophthalmologist.

OK, we've covered diabetes at length time to move on to our second disease, Cushing's and as you can see, and you can see here some of the manifestations of Cushing's, band keratopathy, retinal haemorrhage, 2 case. Of dry eye and a case of Horner's. Let's go quickly through the manifestations of Cushing's in our patients and really the pathogenesis of manifestations of Cushing's is very complex.

Here is a table that tries, . To, to show, it, so we may have the pituitary lesion that's causing, Cushing, and if it's a pituitary lesion, patients may present with blindness, anisocoria or strabismus depending on which cranial nerves are affected. That's responsible for the production of excess cortisol, which may lead to hyperystemic.

Hypertension and sorry systemic hypertension and retinal lesions similar to the diabetic retinopathy. I just, I presented earlier with diabetes meditus, we also see it with hyper uhosteronemia. The excess cortisol will cause ectopic calcification.

I'll show you an example of bankeropathy in a minute, impaired healing. Just like with the diabetic patients that we discussed, and again, due to the pituitary lesions, we may get facial paralysis, we may get exopthalmus, both of them will trigger exposure and again, leading to ulcerative caratitis. And on top of everything, Cushing's has been associated with SARS.

I'll touch briefly on that in a minute. But as you can see, lots and lots of manifestations for Cushing's. The first one is banned, sorry.

The calcification of the cornea, here is a study again, out of the United Kingdom, Jay Samson, one of the first veterinary omologists in England, now retired. Looking at 21 eyes with a calcification of the cornea. As you can see here, many of them because of the calcification had secondary ulceration.

I'll touch on that in a minute. Most of them are central. And while the aetiology is unclear, Cushing was suspected in 11 of the 14 dogs.

OK, we're talking about 21 eyes, but 14 dogs. Cushing's was highly suspected in 11 of them confirmed in 2 of them, and 4 of them also had dry eye, which may have been a predisposing factor for the buildup of calcium in the Cornea and here you can see some classification of the cornea figure from this paper. We get.

Other corneal diseases in these patients, these are due. 2, the corneal calcification that I mentioned, just described the facial paralysis, that affects a patient, especially if it's due to pituitary tumour, the exopthalmus, which is a forgotten clinical sign of Cushing's, and because of all of these, again, we may get ulcerative keatitis, we can get exposure. Keratopathy, if the patient has facial paralysis and ophthalmus, you will get exposure of the cornea.

We'll get dry eye. Here is the paper from by David Williams from Cambridge that I mentioned earlier, showing that in all of the diseases we'll be discussing diabetes, Cushing's, and hypothyroidism, patients are characterised by reduced tear production. And therefore, in any case of a non-healing or progressive corneal ulcer, please consider diabetes mellitus as I described previously, but you should also consider Cushing's as another differential.

Cushing's, just like diabetes, causes not just extraocular disease or ocular surface disease, it also causes intraocular disease. Yes, Cushing's is also associated with cataracts, not as much as diabetes, but it is associated, especially in miniature schnauzers and we all know their lipid metabolism problems. So that may not be surprising.

They get the perm retinalis just like the diabetic patients that, I showed you earlier, and because of the excess cortisol, we get systemic hypertension leading to retinal haemorrhage, punctate retinal haemorrhages. Again, diabetes mellitus is the leading cause, but you also have to consider Cushing's disease. Just one slide about SARS, a sudden acquired retinal degeneration syndrome, and that's because it was extensively covered in a webinars some 2.5 years ago when we spoke about acute blindness, but This is one slide out and I'm of that talk, and I'm just quoting this study out of University of Madison, Wisconsin, looking at sex hormones in dogs with SARS.

So these are dogs with no history of exogenism. Glucocorticoid treatment, but despite the lack of exogenous glucocorticoid treatment, you can see that many of them presented with polyuria, polydipsia, polyphagia, weight gain, increased ALP, ALT, cholesterol. It really suggests that these patients have Cushing.

They also have systemic hypertension, elevated enzymes. They don't have a true Cushing. Again, this is covered in the webinar that we I presented 2.5 years ago, but there is some association between the two diseases association that we don't yet fully understand.

Maybe one day we'll have a better understanding of the causes and treatment of SARS. Moving on to the 3rd hy endocrinological disease that I want to cover today, hypothyroidism. And hyperthyroidism also has ocular manifestations.

A leading manifestation is what we call band keratopathy, reported by Sheila Crispin and Keith Barnett, again, two of the founders of, veterinary ophthalmology in the United Kingdom and in Europe, . Keith Barnett unfortunately passed away a few years ago. Sheila Crispin rose all the way to become a head of the Royal College of Veterinary Surgeons and happily retired a few years ago and her area of specialty was, the othalmic manifestations of hypothyroidism and because of the altered lipid metabolism in these patients, obviously they develop hyperlipidemia.

And hyperlipoproteinmia leading to this strange lesion called arcus poids cornea. As the name implies, it has the shape of an arc that you can see or crescent in both of these patients. And if you look closely in both of these patients, we have an area of clear cornea between the deposits.

We're talking about crystalline deposits. Of lipids or lipoproteins. So here is deposit, but in both patients, you can see an area of transparent cornea between the limbus and the crescent and that should clue you in that you're looking at arous lipid cornea, and your patient should be worked up for hypothyroidism, especially if it is a German shepherd.

Once again, hypothyroidism, is associated with lower tier production. Again, the paper by David Williams, they have lower tier production, but they don't necessarily develop dry eyes such as you're seeing here, and even without measuring tear production, you know that. This patient has dry eye cause you see the dull looking camera, the dull reflection of the camera flash.

Only about 20% of them develop clinical case, yes, but all of them do have lower tear production and in this case, the the, the loss of tear production is because of. Auto antibodies being produced against the tear gland. We know that hypothyroidism is an autoimmune disease, so it's dry eye.

It's a multiglandular autoimmune disease meaning that the body is producing autoantibodies. Against both the thyroid and the tear gland. It's not as if the hypothyroidism is triggering dry eye or dry eye is triggering hypothyroidism.

No, it's a body producing autoantibodies against both of these glands. So we have Ocular surface disease manifested by the lipid curia, the arcus the poss that I showed you previously, and by dry eye, but we also have neurological manifestations of the disease. We know that hypothyroidism is associated with peripheral and central vesti.

Disease, so patients may present with nystagmus, trabismus. They'll have lots of other signs, but as an ophthalmologist, I couldn't care less about them and we do care about nystagmus and strabismus, seen in 7 or 50 dogs with hypothyroidism, facial nerve paralysis. It is a very common finding, a study out of, again, Cornell University back in 1987 looking at 50 dogs with facial nerve paralysis.

A quarter of them had hypothyroidism, OK? So if you are seeing facial paralysis or if you are seeing corners, yes, you should definitely work up your patients for hypothyroidism. So if we take what I've discussed in the previous 3 slides, we've said that these patients have lipids in the cornea, they have decreased tear production, and they do not blink as they should.

All of that combines into nasty looking corneal or. As you can see here, you can see the significant massive deposit of lipids in the cornea. And if it builds up sufficiently, there'll be so much lipid in the cornea that it would actually crack off and fall, OK?

Like if you're building a pile of salt, if it's high enough, eventually it will, of wet salt, I should say it would eventually crack off and fall down and that's what happened here and causing this, this meto seal, the crater that you are seeing in the cornea. And finally, like the other diseases that I've been discussing like the diabetes, muss and the Cushing, a hypothyroidism is also associated with retinal disease, namely hypertensive retinopathy because of the atherosclerosis. So when we do have atherosclerosis, yes, it, it may be due to diabetes mellitus.

It may be due to hypothyroidism, not due to Cushing's, but again, we will see hypertensive retinopathy. And we will see hyperlipidemia and lipemia retinalis. Again, these are covered by this paper out of UC Davis.

So we've spoken at length about the endocrinological diseases, what I call a few odds and ends, a couple of more endocrinological or metabolic diseases. One is hyperthyroidism, . We've discussed hypothyroidism at length.

I have a lot to say about hyperthyroidism. We don't see it in dogs or rarely in dogs, as you know, it's mainly a feline disease and systemic. Hypertension is very common in these cats with hyperthyroidism and systemic hypertension is a risk factor for hypertensive retinopathy, which is what we are seeing here, a disease characterised by retinal haemorrhage, characterised by retinal .

Detachment. Sometimes we're unable to see the retinal detachment because there may also be high fema, in which case we would need to use our ultrasound in order to image the detached retina that you are seeing here. This is a study out of North Carolina State University, looking at 69 cats with.

Systemic hypertension, 5 of them had hyperthyroidism, so definitely should be on your list of differentials. All of this is covered in a webinar in your archives from a couple of years ago. Again, I apologise, but one slide about human manifestations of hyperthyroidism simply because it is so striking.

This is what a person with hyperthyroidism looks like. They really call it the scary looking. Or the frightened looking person and that's because of the eyelid retraction, lilac that you are seeing here, and exothalmus caused by the swelling of the extraocular muscles.

So really very striking. Presentation, but the problem is really with the myopathy that you're seeing here and the swollen muscles cause that can affect the optic nerve, in severe cases leading to optic neuritis and even blindness. It's called Graves disease if someone asks you about it.

A couple of metabolic, Disorders, hypocalcemia may cause cataracts, and that's because the decreased Calcium levels disrupt the function of the lenticular epithelium and allow inflow of fluid into the lens. Hypoglycemic cataracts, two pictures shown here. They typically appear as multifocal white opacities.

In the lens, it reminds you a bit of a steroid halosis or some cases sinty lens that we're seeing in the vitreous, but it's not in the vitreous. This is in the lens. As you can see, it's a very common finding in dogs and in humans with hypocalcemia also in cats with hypocalcemia and thankfully, it's one of the few cataracts, that we can treat.

If we treat the systemic hypercalcemia, it will hold progression. Hopefully, we catch it at this stage and not at this stage. Hypercalcemia, on the other hand, has manifestations in the cornea and in the conjunctiva, you will get calcification in.

The cornea, as you're seeing in these two patients and in the conjunctiva, as you're seeing in this patient here and in the histology of these patients. And finally, I wanna conclude with the ocular manifestations of dermatological diseases, cause lots of them may be manifested in the eyelids. I always say, the eyelids are really just a piece of skin that happens to be near the eye, but it may be affected by various dermatological diseases.

So if you have Have a patient presenting with a alopecia, such as you are seeing here, you should consider Demodex, you should consider dermatofit, which is what this pug has, or you should consider infection by stuff soointermediate. All of these three infectious agents will present with alopecia. Erythema, scales, and crusts such as you are seeing in these two patients.

Again, dermatopage should be on your list of differentials as should zinc responsive dermatitis which is what this guy has or Panhigus foliacious, which is what this poor chow has with lots of erosion and crust on the eyelid margins as well as on the nostril. Patients that present with periocularritis, may be suffering from ectopic dermatitis, such as you're seeing here, again, alopecia, erythema and hypotrichosis. It may be atopic dermatitis, it may be due to sarcotti cais.

IUD pigmentation. Vitiligo VKH, a disease that causes uveitis and secondary glaucoma covered. In a webinar that I gave March last year, or it may be due to discoid lupus or systemic lupus.

And here we have a case of Ili pigmentation in a patient with PKH or uo dermatological syndrome. Again, watch the webinar from last year where it where it is being discussed. And finally, if patients present with eyelid margin erosion or ulceration, you should definitely consider squamous cell carcinoma in your feline patient, Leishmania, depending on where you are practising, very common in some countries, not so common in others, dermatosis, with all of its different manifestations.

And finally, periocular papules may be caused by ticks, also inflict cholosis or herpetic dermatitis. So that is your list of dermatological manifestations. And finally, I'll try to bring some order into your lives because in many of the diseases we mentioned manifestations in the retina, in the conjunctiva and tear production in the cornea, etc.

Etc. I've looked at the individual diseases and their ocular manifestations. Now, let's tackle it from a different direction and and quickly review what are the Differentials for each and every ocular manifestation.

So if we have corneal opacities, we should consider hypothyroidism, where as we said, the lipids would present in an arc or a crescent shaped lesion. We should consider Cushing, which would. Present like this with a more central deposition of calcium or lipids and we also should consider.

Other causes of hyperlipidemia including diabetes mellitus, pancreatitis, and as I said, patients with hypercalcemia may also present with deposits in the cornea, which leads to a fascinating story. I have to tell you, take up one slide for that is the White tree frog out of Australia that suffered from lipid keratopathy and it was discovered that in this case it's because they were fed crickets. The crickets were fed dog food, so the crickets developed hypercholesterolemia.

They The hypercholesterolemic crickets were fed to the frogs and the frogs developed a lipid keratopathy. So an interesting story, yes, it can, it happens not just in dogs, it can also happen in frogs. Cataracts, you have to consider diabetes mellitus, as we said, you have to consider hypocalcemia and a couple of more diseases that we didn't mention riboflavine deficiency, Menoidosis in Persian cats, a disease of inborn metabolism, and Esano's syndrome, which is what this kitty has faulty cogan mutation leading to the development of cataracts.

And Dry eye Corneal ulceration, the panic uveitis, and retinal haemorrhage, all of them may be caused by diabetes mellitus, may be caused by. Cushing or may be caused by hypothyroidism as we have discussed and as shown by these papers that I've presented. And actually these diseases have one more ocular manifestation that I did not discuss till now, and that is what you are seeing here, intracorneal haemorrhage.

OK. This is haemorrhage in the cornea. You can clearly see it's on the cornea in this patient because you can see it casting a shadow both on the Iris and the interior chamber here too, you can see one blood vessel feeding it and here too you can see one blood vessel feeding it, but it actually, this blood vessel leaked and caused an intracorneal haemorrhage.

Again, a study out of Cornell University, 39 cases and Out of the 39, 23 cases of intraccorneal haemorrhage were caused by a systemic disease, diabetes may with Cushing's and hypothyroidism, the three diseases we've discussed, as well as hypertension and immune-mediated thrombocytopenia. And finally, if we are talking about non-infectious diseases, just one slide devoted to your list of differentials for ocular haemorrhage. Here we're not seeing haemorrhage, we're seeing what's called Rubiosis irides congested vessels in the iris.

Here we're seeing peteria on the iris, peteria in the retina and rein detachment with peteria. In all these cases, you have to consider systemic hypertension. Immune-mediated hemolytic anaemia, immune-mediated thrombocytopenia, which is what this he had, coagulopathies, clotting disorders, DIC platelet abnormalities, toxicities, and various vasculopathies such as polycyte.

Leukaemia and multiple myeloma or other diseases causing hyperviscosity. So, as I said, it could be a very long talk. I try to narrow it down to one hour, but really lots of diseases that you have to consider were presented with ocular lesions or as some would say, the eyes have it.

I thank you very much for attending today and my next webinar with Alphabet will actually be a live webinar cause we will be once again discussing slides and clinical pictures and you'll be voting on them. So that would be a live seminar, webinar, sorry, in December. Hope to see you then.

Thank you and goodbye.