Hello, everyone, and welcome to my talk on inherited retinal diseases. As you can see, it's part of a series about blindness in our patients. In fact, this is the 6th lecture in the series.
I previously gave talks on applied anatomy of the funders, the ophthalmic exam. Acute blindness in dogs, which really talks about acquired retin diseases, optic nerve and central blindness. Earlier this summer, we spoke about blindness in cats, and today, we have the 6th and final talk about inherited retinal diseases which really brings this 13 month long journey to an end.
In fact, inherited random diseases is such an important topic that you can actually find textbooks devoted to it. This one is an oldie but goodie, I think it was published in the 1970s, so you can probably find it on the antique bookshops. However, this one, published by the American College of Veterinary Ophthalmology is a great resource cause it Actually summarises all of the orphanic examinations in pure bred dogs in the United States over a 20 or 30-year period, so literally millions and millions of examinations, making it a very important resource and if you hang around till the end of my lecture, I'll actually give you the website where you can download this book for free.
And it's really something that I use every time and every week when I'm on clinics, when my students come and tell me that there is a minture poodle or a golden retriever or whatever waiting for me downstairs in the exam room. As I walk down the stairs, I'm already running in my head the List of inherited eye diseases of miniature poodle or golden retriever or whatever the case may be, cause there is a fair chance that whatever the patient came in for may be an inherited disease and today we'll be talking about inherited retinal diseases, causing blindness, . There are scores of diseases.
I'll not be able to mention all of them. Some of the ones I'm not mentioning are in the notes and handouts that are available on the website. We we'll be talking about retinal dysplasia, about coli I normally, about PRA progressive retinal atrophy, now known as PRCD and perhaps most importantly, what can we do about it and how can we try and eradicate these hereditary eye diseases that cause blindness in our patients.
So the first disease we're going to talk about is rettal dysplasia, which is a congenital abnormality due. During developmental or embryonic, stages, leading to abnormal retinal differentiation that results in folding of the sensory retina shown here histologically we are We know that the retina is supposed to lay flat against the choroid which you're seeing here, and instead of being flat, you see this fold here that someone decided to give the very picturesque name of Rosette, maybe because it resembles a rose. We see rettal dysplasia in many species.
However, in many of them, it is acquired due to maternal infection, for example, in cats due to FLLV infection, in cattle BVD and in sheep due to bluetongue infection or maybe maternal toxicity during pregnancy. However, we're talking about dogs today and in dogs, it is an inherited disease, topic of my talk, and it, that makes for a very significant disease found in many breeds. You can see that it is autosomal recessive in the cocker spaniels and interior breeds.
It's dominant with incomplete penetration in Labrador retrievers and in the American Pit bull terrier. It's also common in beagles, Australian shepherds, Dobermans, etc. Etc.
So you can really see that it is inherited in many of the most popular breeds around in which it presents in one of four forms. The first form and perhaps the most common one is what's called the focal or the multifocal form, whereby if you look at the fundus, you see grey streaks. In the tapetal area, you see white white streaks in the non-tapetal area and this, as you can see here, can be linear.
They can be Y shaped or V shaped and really, you are seeing these folds in the retina, you're seeing the rosettes that I mentioned earlier. This type of dysplasia is not progressive. As I said, it's a gentle vision and it will not progress, it will not, become worse, and it has minimal effect on vision.
So obviously, any of these tricks forms a blind spot in the visual field. However, These are small blind spots and one eye always compensates for the other, so really the owners will not notice any effect on vision. And here is a list of some of the breeds in which we find the focal or multifocal form.
A more severe form is the geographical dysplasia, where as you can see in these two pictures here, we are seeing a larger area of detached retina or atrophied retina. You can see the elevation here in this area. You can see that the tepium.
It is slightly hypo-reflected because of the detachment. You can see that sometimes it has a pigmented border such as on the picture on the right, and because we have a larger area involved, vision is obviously affected, but still, if it's just one eye, cause it's a full collision and one eye compensates for the other, the owner may not notice any behavioural effects. And again, this form is also common in some of the more popular breeds and here is a picture showing again a very dramatic case of the multifocal form and another example of the geographical dysplasia.
Things become more serious when you are talking about complete dysplasia, which causes a complete retinal detachment. You can see here a fully detached retina ballooning out towards you and here you can see it. In a sagittal section of an eye that's been nucleated and we are getting the classic seagull sign of a detached retina connected to the globe, really only the optic nerve area and in the very periphery.
Obviously, such eye is blind, the patient will also present with severe nystagmus, and when you examine it ophthalmoscopically, that's what you will see. Sometimes you may also find dysplasia of the vitreous and retinal haemorrhage. And again, here are the breeds, Lee Bedlington and Cham Terrier and the English springer spanning.
1/4 form and also quite serious form is oculoskeletal syndrome, which, as the name implies, combines both retinal dysplasia and chondral dysplasia causing in the eyes, cataracts and retinal detachment, as you can see here and in the skeleton limb deformities, so you can see two litter mates. One is a normal dog and the other one is an affected dog, obviously much shorter than the littermate, . And there may be other skeletal abnormalities associated with this presentation that we see in some the Labrador retrivers, and this is one form of retinal dysplasia for which we have identified the causative mutation, a very important point I'll come back to at the end of my talk.
What can we do to prevent retinal dysplasia? Well, we can screen all dogs for retinal dysplasia and as I said at the beginning of my talk, when I showed you the blue book by the American College of Veterinary Ophthalmologists. Breeders do bring their dogs in for screening, so we screen, for rein dysplasia cause forms one and two, the focal, multifocal and geographical dysplasia, as I said, have minimal effect on vision.
The owner will not notice it, so really these forms are discovered only during screening and if you see. Retal dysplasia, and again, here is a nice picture of, of the multifocal dysplasia, then we discourage breeding of any affected dog. Now, I know some of you may be scratching your head.
Why should I discourage breeding of this dog if I said that it really has minimal effect on vision? And the answer is that even such a mild multifocal form that has a minimal effect on vision. Could give birth to a litter of dogs with complete retinal dysplasia, a litre of blind puppies, and therefore would discourage breeding of dogs with any form of rectal dysplasia.
The second disease I want to talk about is coliI anomaly, which is a disease with worldwide distribution affecting 30 to 85% of the smooth and rough cos worldwide. I'll show you figures in the next slide. So really a very, very common disease in collies, which is why it's called coli anomaly, even though it may be found in other breeds including the Shetland Sheepdog, Langshi, healer, Australian shepherd, and other breeds.
Here, for example, is a study from Switzerland by Bernard Spiace, one of the first veterinary ophthalmologists in Europe who looked at the prevalence of colii normally in Switzerland. He examined over 3500 dogs from the breeds I've shown you in the previous slide. And as I said, rough coli, 37%, more than a third of the rough coli in Switzerland are affected.
And as you can see, it's also very prevalent in the Shetland chip dog and in the smooth coli, and again, you'd get the same picture or even the worst picture in other countries. So what is chole anomaly? The definition is a congenital choroidal hypoplasia.
So just to remind us what is the choroid, here we have a diagram of the eye consisting of three layers. The outer layer in blue is the connective tissue, the cornea, and the sclera, the innermost layer, the retina in red, and in between them in yellow is the uvea, the iris, the ciliary body. And the choroid which provides blood supply to the photoreceptors, so it's situated between the sclera and the retina, and here you can see the choroidal blood vessels wrapping around the entire retina around the entire globe and coli anomaly we are talking about hypoplasia of these blood vessels.
Clinically, we look for lesions that are located temporally or dorsal temporally to the disc. And in those areas, we would see focal absence of the tepitum and the Pigment of the retin pigment epithelium, which allows us to see abnormal choroidal blood vessels. And when I say that they are abnormal, they are fewer in number, they are wider, and they are abnormally oriented.
So I'm talking about this lesion, this presentation here. Here are a few more pictures. Let's begin with the normal one which shows you normal paroidal blood vessels.
I'm able to see it in this eye cause it's an albino eye and you can see that coridal blood vessels converge on the discs, so they are radial blood vessels looking like thick bands, you will call it tigroidtepetum cause it resembles the stripes on a tiger. You can see that in all of these three eyes in the area that's temporal or dorso temporal to the disc, this area has fewer choroidal blood vessels. You can compare it very well to the normal choroidal blood vessels that you're seeing here.
You're seeing fewer blood vessels. They are much wider than the other choroidal blood vessels and they are sometimes abnormally oriented. So this would be the classic presentation of choroidal hyperplasia.
Unfortunately, that's not the only problem in coli eye anomaly. 10 to 30% of the dogs also suffer from optic nerve coloboma, meaning, that there is a piece of the optic nerve missing and obviously that would cause significant visual deficits. This is what a coloboma, a large coloboma would look like histologically, you can See here that a piece of the optic nerve is missing and this is what it looks like ophthalmoscopically.
Here is a small coloboma, here is a huge coloboma. So it looks like a white great indentation on the surface of the optic disc. And as you can see in this picture, and this picture here and here, when the blood vessel The right blood vessels arrive at the edge of the coloboma.
They sort of disappear from view cause they fall to the bottom to the pit of the coloboma. So instead of seeing blood vessels here on the disc surface, they arrive at the edge of the coloboma and they dive in, which is why we're not seeing any blood vessels on the coloboma. And here are a couple of more pictures showing you a small coloboma and a huge coloboma really involving the entire optic nerve head and obviously this eye would be blind.
As if this was enough, 2 to 10% of the dogs will have retinal haemorrhage or retinal detachment, and obviously just like the colobomas, this also cause visual deficits. You may see very tortuous retinal blood vessels, and it's been shown that affected dogs will give birth to a small litter. Cole anomaly is inherited as an autosomal recessive disease.
In 2007, we were very excited when a causative mutation was identified by Parker in this gene. However, it is probably not. The complete story cause for example, we have a study out of Denmark showing that a mutation in this gene causes coli anomaly in the second sheepdogs in Denmark, but not in the rough coli in Denmark.
And you can always ask yourself how would a mutation in just one gene cause both a severe form of the disease such as this one or just a mild form such as this one. So perhaps there is some modifier gene that is also involved, excuse me, in the pathogenesis of the disease. It's very difficult to eradicate coliiron normally despite our best efforts, and that's due to several reasons.
The first one is what we call a go normal phenomenon. Go normal phenomenon means that The dog is born with choroidal hypoplasia. It is born with these lesions that I've shown you here.
However, as the dog matures, these areas may become covered by pigmented retinal pigment epithelium and if they are covered, you'll no longer be able to seize them. So they exist. In this dog right about here, but you're unable to see it because it's been covered by pigment and this is a phenomenon that we see in about 50% of affected dogs and that's why if you want to screen cos for coli I anomaly, you should really screen them at 7 to 8 weeks of age before the lesion may be covered by the pigment.
Another problem is that the choroidal hyperplasia does not cause visual deficits. On the optic nerve coloboma does. So breeders may tend to downplay the importance of the disease.
And the third reason is that it is such a prevalent disease, that it would really be almost impossible to eradicate cause when 30 to 80% of collies are affected, obviously, you cannot take so many dogs out of the genetic pool, out of the breeding stock. You'll always have, the disease left in the background. It would be a very, very long effort spanning many, many decades to eradicate it.
We may have better luck with the genetic test, checking for the NHEJ1 gene that I mentioned earlier. However, there are still no reports about the sensitivity and the specificity of this test. And therefore, because of all of these reasons, coli I anomaly still remains as a very, very prevalent disease.
The last disease I want to talk about is the most common one and the best known one, PRA progressive retinal atrophy, even though today it would be more correct to call it PRCD progressive rod cone degeneration for reasons I will shall soon explain. And actually, you can see that I am putting progressive retinal atrophy in quotation marks because as our understanding of the molecular basis of the disease and the genetic basis of the disease has expanded in the last couple of years, we've really discovered the PRA is The catch-all phrase for a large number of diseases, that differ, as I said, in their molecular and genetic aetiology, as you'll show in a minute. The reason I'm showing in Irish setter here is because Irish setter is the breed in which PRA was first described by Perry working at the Animal Health Trust back, I think in the 1940s and he did a very elegant study of PRA in the Irish centre but since then we have discovered that really it affects a large number of breeds.
In fact, here is a list of breeds that's affected by PRA and As I was trying to say earlier, various breeds are affected by various forms of the disease, and I know this is a very small print, you may not be able to see it, but, you can see that, the Alaskan mall which is affected by, and the Australian shepherd are affected by cone degeneration, other breeds such as the Belgian shepherd may be affected by photoreceptor dysplasia. Bernie's mountain dogs has the good old PRA progressive re atrophy. We are, talking about the American cocker spaniel with progressive rod cone degeneration.
We are talking about the American pit bull terrier with cone rod dystrophy. So really, lots of forms affecting various breeds, all of them. Historically are known as PRA, but again, now that we are more aware of the Molecular and genetic basis for these diseases, we know that they're really different diseases.
They vary not just in the form, they vary in the age of onset. Some breeds such as the coli or the Irish setter are affected by dysplasia, meaning that, we see the disease at a very early age in the Irish setter, you can see that we are seeing ophthalmoscopic and behavioural signs of the disease, when the animal is 12 to 16 weeks of age, for thermoscopic signs, 6 to 8 weeks of age for behavioural signs. Same for the collie, we're talking about 6 weeks of age when the disease is first manifested.
However, in other breeds that suffer from PRCD from the progressive rod cone . Generation, such as the English cocker spaniel, you are seeing that the disease is manifested at 4 to 8 years of age of thermoscopically, 3 to 5 years of age, behaviorally, so a late onset disease. So we have variability in the age of presentation, we have variability in the affected cells.
Most forms of PRA begin as rod degeneration which progresses to affect cones. So we are talking about progressive rod cone degeneration or rod cone degeneration. Some diseases take the opposite course.
They begin as cone degeneration which spreads to rods. We're talking about the duns and the pit bull, for example. So this would be CRD.
Cone rod degeneration rather than RCD rod cone degeneration. Some of them have just cone degeneration and others such as this dog here, an English springer spaniel would have RPE dystrophy, so the retinal pigment epithelium is affected, so really various cells in the retina may be affected in the course of the disease. And not only do we have variability in the age of onset and the affected cells, we also have variability in the mode of inheritance.
So most forms of quote unquote PRA are inherited as autosomal recessive disease. However, in some breeds such as the Siberian husky, we may see excellent disease, we may see dominant disease in the mastiff and bull mastiff, we can see in complete dominance and just To make things more complicated. Sometimes we have two forms in the same breed.
So, Abyssinian cats, I know this is a talk about dogs, but the most radical dramatic example is abyssinian cats that have a dominant early onset form of PRA and a recessive late onset form of the disease. So different manifestations in the same breed of animal. And all this variability in the forms of the disease, in the age of onset, in the affected cells, in the mode of inheritance are really due to variability in the genetic mutation in the causative mutation.
Here is A cartoon showing the biochemical cascade that takes place in the retina, when a photon of light is absorbed by the photopigment in the retina, triggering a biochemical cascade that culminates in the closure of a cyclogenated sodium channel, leading to hyperpolarization of the photo. Receptor. This would actually summarise the 1967 Nobel Prize in Medicine cause this really explains how we see how the absorption of light causes hyperpolarization and the neuronal signal.
As you can see, there are many enzymes and proteins involved in this cascade and PRA or the various forms of the disease that I described earlier, the PRCD and the RCD and the CD etc. Are due to mutations, different mutations in the different enzymes involved in this cascade. And there are literally scores of mutations that have been identified in all of these proteins, and each mutation would cause a different form of the disease.
So for example, earlier I said that both Irish setter and collies are affected by Rod cone. Dysplasia, however, the Rod con dysplasia in the Irish set and in the coli is due to different mutations. So the Irish setter is affected by RCD1, Rod con dysplasia 1 mutation, and the call is by RCD2, which really means that if you take An infected collie and an affected Irish setter breed the two and you will get a seeing dog.
The dog will not be blind due to dysplasia. It will be a carrier of both mutations, but these are two different mutations and therefore, yes, you can take two affected dogs with retin dysplasia, breed them, and the dog will be visual. However, no matter where in this biochemical cascade, the mutation is located, the end result is similar in all cases and all breeds and the end result would really be the failure of this Cygated sodium channels to close and there will be no hyperpolarization, there will be no vision and the eye will be blind, but all of the variability I've said I described earlier is due to where the mutation is located.
So how do we diagnose PRA now that we understand what PRA is, we can do it based on behavioural signs and the history given by the owner based on the clinical signs that we see in the ophthalmoscopic examination, ERG where we record electrophysiological activity in the retina and genetic testing. So, history would depend on the form of the disease. If it's cone degeneration, the dog would be day blind.
If it's cone rod degeneration, it would start as day blindness progressing to night blindness, but as I said, the most common The form of the disease is PRCD progressive broad cone degeneration. So as the name implies, we will get progressive loss of vision beginning with night blindness cause rods are affected first, then. That would progress to loss of cone function culminating in total blindness.
And as I said and I've, as I've implied earlier, while the progression is the same, the age of onset would vary according to the different rate depending on where that mutation is. Located, but that is the course of behavioural changes in the dog. And my students are taught that whenever a dog presents for progressive loss of vision, the first question to ask the owner is whether it started out with Loss of nighttime vision.
Now, as I've said in one of my earlier blindness lectures, be very, very careful about how you phrase this question. Don't ask owners, did loss of vision begin as loss of nighttime vision cause owners almost always automatically say yes. Did the beginners loss of nighttime vision?
Yes. . Does the sun rise in the west?
Yes. Is Paris the capital of England? Yes.
OK. They, they just want to make you happy. So try and phrase your question in a neutral sort of way.
Was there a difference between nighttime vision and daytime vision? And you'll be surprised by how often they say, you know what, you're right. It started out as loss of nighttime vision.
Ophthalmoscopically, we are talking about a bilateral disease, so both eyes are affected though not necessarily symmetrically. In the early stages, we are seeing changes in the peripheral retina cause again, we're talking about progressive rod cone degeneration, rods are located in Periphery of the retina cones are located in the central retina, so we are seeing great discoloration in the peripheral topitum and some blood vessel attenuation. So you're seeing this grey shading grey discoloration.
In the periphery and you can see some attenuation of the blood vessels, they are not as wide as they should be and that's because as the retina is atrophying in the periphery, it has less demand for blood supply, so we start seeing regression of blood vessels. Which is more obvious here. I know that sometimes people have a hard time saying, well, is this a normal looking blood vessel or not?
Is this one a normal looking blood vessel or not? The trick you could use is count the number of bifurcations in a blood vessel. If you can see 33 bifurcations.
Or more, that's OK. Here, I'm seeing one bifurcation, but I'm not seeing a second there, another one coming off this blood vessel. I am very, very suspicious and in fact all this area is devoid of blood vessels, so yeah, this is OK.
Here, yeah, again, I'm seeing a first bifurcation, but then I'm following this blood vessels all along. Maybe here, no, this one belongs here, so no additional bifurcations. So just count the bifurcations and see if you can get 3 or more and obviously here we will not see them.
As the disease progresses, we get cones affected, so the disease moves from the periphery to the centre and we start seeing total hyperreflectivity. Why are we seeing total hyperreflectivity? Well, this drawing here reminds us that the tepium is located behind the retina.
So there is A transparent retina between us and the tepitum and therefore we see the tepitium clearly. However, as the retina becomes thinner, we do get increased. Reflection from the tapetum simply because of the thinner retina, that's between us and the tepitum.
So tepital hyperreflectivity and accompanied by additional blood vessel attenuation is more and more. Of the retina is atrophied and here you can see in these pictures, significant hyperreflectivity, it's not because of overexposure of the pictures, it's just that these retinas are atrophied, accompanied by Attenuation of the blood vessels until you get to such a dramatic stage where basically complete hyperfectivity and absence of the retinal blood vessels. Note the differences in shape of the optic nerve head between those two pictures, this would still be normal.
This one is already grey, around and atrophied. So that's another change we're seeing is atrophy of the optic nerve head and some modelling in the non-typetal area. Animals will present with abnormally dilated pupils.
However, as I've said in one of my earlier talks, the PLR will usually be present, because it doesn't take too much effort. Input to trigger a PLR. So even if your retina is 90 or 95% atrophied, the 10 or 5% of functional retina that's still there will be enough to trigger PLR.
Unless right now is 100% atrophied, you will get PLR though it may be diminished. Cataracts gets, two question marks here. Yes, we see lots of dog breeds with both PRA and cataracts, and there is a big debate, or I, I wouldn't say debate, a variation.
Sometimes we are talking about two separate hereditary disease. Yes, this dog suffers from both. Hereditary PRCD and hereditary cataract.
Sometimes the cataract may be secondary to PRA cause the free radicals that are discharged by the degenerating retina will cause cataract and sometimes advanced cataract will trigger lens-induced titis causing secondary retinal degeneration. So these are the ophthalmic signs of the disease. One more way for us to diagnose the disease is through electroretinography, electrophysiological recording of retinal function.
Back to this table that I showed you earlier with the different dog breeds, different forms of the disease, the age of onset of ophthalmoscopic signs, behavioural signs, and now I've added another column, the age of onset of ERG abnormalities. And you can see that in some dog breeds like for example, the Akita, there isn't much of a difference between the age of onset of ophthalmoscopic signs, behavioural signs, and ERG abnormalities. They're all at 1.5 to 2 to 3 years of age.
Same with the Tibetan terrier here, for example, 10 to 18 months, 6 to 12 months, and 10 months of age, not much of an advantage for an ERG or no advantage whatsoever. However, look at the Siberian husk in the Samoyeds, 1.5 to 2 years of age for thermoscopic signs, 2 to 4 years of age for behavioural signs, 6 months for the ERG abnormalities.
That's a significant difference and that's very important to breeders who want to know whether the dog is affected. They don't have to wait till the dog is 4 years of age. They can get an electroretinographic diagnosis at 6 months of age.
And sometimes it's even more dramatic. The miniature schnauzer, for example, 1 to 2 years of age, 6 to 12 months of age, 6 to 8 weeks of age when you're seeing the ERG abnormalities. So that makes the ERG a very, very powerful tool for early diagnosis.
However, in recent years, as we have started identifying the causative mutations of these diseases, ERG is getting replaced by DNA testing. Which always brings up a question that owners will ask you about whether they should do genetic testing for hereditary eye disease or family examination for hereditary eye disease. It's a question that, yes, you will get asked very often and that's why I'm going to devote some time to helping you answer this question.
So there are significant advantages to genetic testing. Number one, it can be done at any age. As soon as the puppy is born, you take a chick swab, or blood sample and know whether or not it is carrying the mutation.
So it gives it, so genetic testing is predictive, even if the dog is not yet affected by the disease. You know, whether or not it will develop the disease. And another very, very important advantage of genetic testing is that you can detect carriers, heterozygous carriers.
Again, I remind you that most of these diseases are autosomal recessive, so it's important to detect carriers to plan the breeding of affected animals. So yes, there are great advantages to genetic testing. However, there are also disadvantages to genetic testing.
Number one, you are testing only for a specific disease. You are sending it off to be tested for a mutation. The dog may have other inherited eye disease.
So here is a page, a web page from one of the testing companies, and you can see that, yeah, you can test for Rodcom dysplasia and you can cause a test for the PRA and you can test for heredity cataract, but each one of them is a separate test, OK? So if you want to test for broad cone dysplasia, that's $100. And then if you want to test for rein atrophy, well, that's another $100 and cataracts another $110 and that soon accumulates to a pretty impressive bill.
And again, you're testing just for this one or two or three diseases. The dog may have other inherited eye diseases, it's not being tested for. Maybe because you're the breeder is unwilling to pay, maybe because the causative mutation has not been identified.
A great example for this is cataracts. Cataracts affects scores of breeds, maybe 100 dog breeds have hereditary cataracts. However, the causative mutation has been found only in the Australian shepherd.
Boston terrier, French Bulldog, and then Staffordshire bull terrier. Only in these four breeds. If the owner, the breeder has any other dog breed, he or she is unable to test for hereditary carrot, so that's a significant immutation of the genetic testing has the mutation been identified.
Also, Accuracy depends on the lab quality. They are doing PCR for their genetic testing and as we've found out nowadays from all the PCR testing for Coronavirus during the COVID epidemic, not all labs are equal and some are better quality than others and that's why you have problems of accuracy and also problems of honesty, if the breeder sends the sample to the company. We really have no way of knowing whether he sent it from this dog or that dog.
They just fill out a declaration online, but we don't really know whether, the dog, the, the sample came from the dog that, the details are provided on the form. The other alternative is the ophthalmic examination, which has the opposite disadvantages and advantages. It can only identify existing diseases, unlike genetic testing, we don't have predictive power.
If I don't see a cataract nowadays, if I don't see PRA today, it doesn't mean that the dog won't develop cataract or PRA. A year or two down the road, which means that the dogs will need to be reexamined every 1 or 2 years and in thermoscopic examination, I cannot identify carriers. However, there are great advantages in the fact that I perform a comprehensive eye exam, starting with the eyelids and, and looking for entropo and entropion, and dysthia and tracheasis going all the way to the back of the eye and the retina.
So I'm really I'm covering all of the eye during my exam and all and checking for all possible disease and number. 2, as you'll see in a minute, I am required to identify the dog by a microchip or the 2. So when the owner gets a certificate, we know that yes, this is the dog that's being tested.
So, as you can see, really, the genetic and the examination in a way complement one another in their comprehensiveness, their accuracy, and their predictive power. Which leads me to the last topic, what can we do about it? And both in Europe and in the United States, we do have programmes for rad.
Ating hereditary eye diseases during which dogs are examined by specialists, and I stress specialists because you need to be trained to identify some of these diseases, especially in the early stages. So general veterinary education is not enough. The examiner identifies the dog by the 2 or a chip.
And you record the results of your exam on an international forum. This is a form of the European College of Veterinary Ophthalmology, which is accepted in most countries in Europe. A few nations will have their own national form.
Based on the results of our examination, the owner gets breeding recommendations. He or she gets the certificate and if they look up the blue book or websites that I'll be sharing with you in a minute, they get reading recommendation. 10 diseases come with a recommendation of do not read.
Other diseases that are more moderate or have less clinical impact, we let the owners or the breeders decide whether or not to breed. So for example, here is the breeding advice for the Alaskan malamute. You can see that obviously we do not want any dogs with glaucoma bred because it's a horrible.
Disease that leads to blindness. We don't want any dogs with cataracts spread. We don't want any dogs that are blinded by cone degeneration bread.
However, if it's just to stick a few extra eyelashes or some corneal dystrophy, let the owners decide. We cannot take every dog with the, with minor inherited eye diseases out of the genetic pool. So in these cases, we let the owners and breeders decide, the owners, I should say, and the club, and their decision would be based on how large of a breed is it.
So if you're talking about a breed with very low numbers like Like the Shiba Inu or the Japanese chin, it would be more difficult to take out dogs from the breeding pool and the genetic pool because it's such a limited pool to begin with. Breeds that are more popular, such as cocker spaniels or Labradors, your job may be easier because it's possible to take out, of the breeding pool affected dogs. It depends, as I said, on the severity of the eye disease, glaucoma versus dysthychia, and are there other serious health problems in the breed?
I am an ophthalmologist, but with all due respect to ophthalmology, you know, we, there are other hereditary problems, the dogs may be suffering from, hip problems and cardiac problems, etc. Etc. You don't want to increase the prevalence of other problems by taking out too many dogs.
So the owners and the breeders decide what to do. With our recommendations, the big question is really do they publish the results or not, and this policy varies from country to country. Sometimes the breeder keeps the certificate, the copies of the certificate, so he or she can share it with other breeders interested in breeding their dogs with him.
Sometimes they are published online anonymously. Which sounds sort of useless to me. Sometimes the breeder decides whether or not to publish the results, which means that we see that only if the dog got a clean bill of health, they'll be published.
And really, the best way to go about it is if all results are published online. This is commonly done in most of the Nordic. Countries in Germany, in the United Kingdom, I know that many people in the audience are from England.
So here is a website of the Kennel Club where you can go, where breeders can go. They put in the dog number and they will get the results of of of oral examinations if such examinations work on. And they know whether or not they want to mate their dog with this dog.
And yes, you can see that Mate Select, this website is being used to promote sustainable breeding of pedigree dogs and there are lots of papers about it. So that makes it for a very powerful tool in the eradication of hereditary eye diseases. How powerful?
Well, I'll just show you one example. Here is an article describing how, such selective breeding, repeated eye examinations and the breeding advice generated by these eye examinations affected, the prevalence of hereditary eye diseases in German ducko. It's a 13 year old, a 13-year study during which 13,000 ducksunds were .
Examined and because of the screening and the preventive breeding, you can see that the prevalence of cataracts was reduced by 2/3 from 8.7% down to 3.1% and PRA or PRCD which is an Untreatable retinal degeneration decreased by 90%.
So yes, the advice is that if these breeders bring their dogs to be examined and if they follow advice, they can improve the health of their puppies significantly. Here are some more examples from the United States. Again, I'm referring to the blue book that I mentioned earlier and as I said, it's a very powerful tool cause it summarises a great number of ophthalmic examinations in all of the breeds.
So if we are looking for example at the Labrador retriever, you can see that 91 to 99, 60,000 dogs were examined and another 64,000 were examined 2000 to 2,0005. So I'm talking here. About 125,000 Labrador retrievers being examined.
Obviously a huge database and you can see that based on that, the prevalence of microthalamus, which is a small I, decreased from 0.06 to 0.02, glaucoma from 0.03 to 0, entropion from 0.6 to 0.44.
Etc. Etc. Same with the cocker spaniels, again, huge numbers, 18,000 and 14,000 dogs examined and you can see reduction in the prevalence of diseases and German shepherds, etc.
Etc. So a very, very powerful tool if only breeders decide to use it. I promised you that I'll let you know where to find the book.
So here is the website that allows you to load the blue book for free if you have a VPN that allows you to disguise where you're from cause it's only available to those in the UN so you need a In the United States, sorry. So you need the VPN if you're outside the US and then you can download the book. The ECBO website, the European College of Veterinary Oophthalmology also has a free book there without the numbers, but with lots of free advice, especially about genetic, .
About genetic testing, the British website of the BVA and some websites, commercial companies that performed DNA testing. I understand that the Animal Health Trust has shut down due to COVID-19, but hopefully it will reopen in Cambridge University from what I'm hearing. Other than prevention, what can we do about hereditary eye diseases?
Well, we can't really treat them. We can just educate the owners and, explain to them that blindness is not an indication for euthanasia. I often get, when you're saying, oh gosh, my dog is blind, I'm going to euthanize it.
No, you know, as long as it's not painful, it's no reason for euthanasia. If it's uncontrollable glaucoma, yeah, . Euthanasia or no, we don't euthanize, I'd say nucleation.
Uncontrollable glaucoma may be an indication for a nucleation, but you don't nucleate the dog simply cause it's not seen just like you don't nucleate blind people. And basically, you tell the owners that this is progressive blindness, the dog has time to adjust. It's non-painful.
It has no Systemic effects. It doesn't have cardiac or hepatic manifestations. It's just limited to the eye.
So, yes, dogs can learn to live with it. They'll unfortunately be blind, but they can adjust and here's a website that I send owners to. With lots of useful advice, such as this hoop that's mounted on this dog, or if the owner has a couple of dogs, they should put a bell on the collar of the visual dog, and the blind dog will learn to follow in the footsteps of the visual dogs.
You can buy a book in this website and the dogs will adjust. Just a few more slides about maybe what will happen if I were to give this talk 5 or 10 or 15 years from now. Well, maybe 15 years from now, we shall be able to treat these hereditary eye diseases and that's because as Humans also suffer from very diseases that are very similar to PRA or PRCD so much research is being done in these dogs as animal models for blindness in people.
Here is something that almost sounds like science fiction, we are talking about retinal prosthesis. The person is wearing glasses mounted with a small camera. The camera takes a picture of the outside world, broadcasts it to the chip on the retina, and conveys an image to the brain.
If you don't believe me. Here it is. Here is retinal prosthesis in the fundus of a dog because the dog is an animal model for this human was implanted with an artificial retina.
If you go to this website, you'll see some amazing movies. It sounds like science fiction, but you will see people who regained vision thanks to an artificial retina. Stem cell therapy is done whereby they take Embryonic stem cells lead to differentiation of retinal neurons and inject them into the retina in order to restore visual function.
You can do gene therapy whereby you take a virus, you remove the pathological and replicating genes from the virus and replace them with the gene that the patient is missing, you. Inject the virus to the target organ in our case, the retina, the virus will infect the photoreceptors, deliver the gene and the cell will begin to express the normal protein. I'd like to end with this one movie showing you.
How rein gene therapy is done. Here is a fine cannula going into the fundus in underneath the retina, and now it's injecting the vector. You can see the subretin bled because of the fluid containing via vector that was injected subretinally and if everything works.
Then the animal regains vision. That was actually a picture from my own personal lab where we're working on a ship model of day blindness and with this simple injection, the animals have regained vision for 6 years and counting as the title of our paper from 28. Says, now, in fact, we are up to 9 years and counting and believe me, there is nothing more thrilling to a veterinarian or a veterinary ophthalmologist than to take an animal that's been blinded by hereditary retinal degeneration, perform a single injection, and the animal regains vision for 9 years and counting.
So as I said, this ends our 13 month series on blindness in our patients. If you've missed one of my talks, they're all available for viewing on the website. I thank you very much and I'll be back in December for a quote unquote regular talk, we'll not be talking about blindness.
We'll be talking, the title of the talk is a cat is not a small dog. What are the differences in ophthalmic diseases between cats and dogs. Thank you very much and stay healthy.
Bye-bye.