Hello, this is Henry Shyman. I'm the clinical leader of the local oncology unit at the Royal Liverpool Hospital and this presentation is on the management of pediatric and be 9 adult ocular tumors.

So we're going to cover the tumors we can see in newborn adolescents and adults, and the most important one is the retinoblastoma. Then we go on retinal astrocytoma retinal angiomas choroidal hemangiomas and retinal vessel proliferative tumor.

Now just a brief recap of retinoblastoma. This is one of the two malignancies that can occur in newborns. The other one is the neuroblastoma and it's a malignant tumor of the developing retinal cells. So once the red on sale has been established, it will not develop retinoblastoma. It can only develop retinal with trauma during the development, meaning this is a tumor that affects only very young children newborns and can develop slowly, so it's only picked up at the age of four or five, but that's about it. There very few.

Cases detected after that in the majority of cases, children zero to six years. The incidence about one in 20,000, and it's the same all over the world, so there's no race predilection as it would be, for instance, for choroidal Melanoma.

In the UK we see about 4050 cases per year and worldwide. That's about 8000 cases on the planet per year.

In the UK, I reckon my stoma patients are treated in two specialized Centers for pediatric oncology and they are located in London, Birmingham. I myself treated the patients in Berlin. Where did my training, but here in the UK you will not see written blastoma patients newly diagnosed. They will go straight to Birmingham or to London.

This is a tumor that if untreated, it will not stop growing, so you may see horrible pictures from the developing countries. It will just continue to grow and destroy. Unfortunately, the face and kill and the child by developing metastasis. However, it's one of the few tumors that if you detected early, the cure rate is almost 100%, so they metastasize very late so you got a good window of opportunity to treat these tumors successfully and what we've seen over the last decades is there's more and more trend towards I saving treatment.

So just looking a bit at the history of the management, all affected children died until the 1900s, and this is when the first treatments were developed. These included in nucleation, so the surgical removal of the affected eye and then radio therapy so that for the first time eyes could be saved and the child could be saved with radio cerap therapy. So these were the mainstays of treatment for 90 years until the 1990s, Sir, when there was a big switch of treatment and I come to that later.

I'm torts chemotherapy, so now almost all advanced cases are treated with chemotherapy.

The state of the treatment at the moment is almost all children survive and can see when treated promptly and in the majority of cases in the advanced bilateral cases one I usually can be saved to just give some vision to the child. The current treatment options depend totally on the extent of the disease, so you got very early disease. Does easily treatable in adverted commas got very advanced disease. It's very difficult to treat and it's a stage dependent approach of the treatments. The earlier diseases detected, the better the chances for good vision.

And these children might come to you. It's covered in a different talk about the signs and symptoms of retinal blastoma, but you may be the first point of call looking at children with rotten blastoma so it's very important to know about this disease. Becausw is the most important, is easy, would have to treat in your daily life.

Just a.

Brief recap of the two groups of Reclama Stoma one's unilateral, and this is about 60 to 70% of cases. Unilateral means only one is affected, the other eye does not have a Recon. Blastoma 85% of these cases are spontaneous mutations. There is no family history out of a sudden, their child develops a random stoma, which usually presents with local Korea, but nothing else in the family history. But you have to keep in mind that still 15% of these cases can be hereditary.

So a child with the uni lateral retinoblastoma. Unfortunately in 15% does have a risk of passing it on to the offspring. The other group is the bilateral and trilateral bilateral is 30 to 40% and very rarely trilateral bilateral means that both eyes are affected by reading list. Oman trilateral, that are they have a midline tumor in the brain in addition to the rectum blastoma in both eyes. Now bilateral trilateral are always hereditary, but only one in four. 25% have a positive family history.

That means the others are the first in the line. To develop these mutations to develop bilateral Mascoma, and if you have a bilateral or trilateral Thomas Toma the risk of giving it onto your spring about 45%. Again, this is covered in the other talk, but it's quite important to understand what's behind this mode of giving it to your offspring.

Now read my stomach and present in totally different stages. Really from very easy to treat to a very difficult, almost impossible to treat. So there's a grouping system and international grouping system. Group A means you have a small tumor in the retinal. This loop, blue little dot there away from the fovea and the disk. These are the ones that usually are pretty straightforward to treat. Group B means you do have either larger tumors outside the centre or smaller tumors more central towards the fovea and the disk.

Group C means that you have some local dissemination of the tumor, which makes treatment a lot more challenging. That usually can be into the vitreous. So from the retina in front, but it can also be subretinal so you can get retinal attachment with a separate on seedings of this tumor, this Group C Group D is diffuse tumor dissemination, meaning you not only have a medium to large size tumor, but you have diffuse seeds in the. I usually in the vitreous can be in the anterior chamber as well lot more challenging to treat.

And finally, groupies extensive tumors inside the air. More than 50% of the globe. Or you get an ear vascular glaucoma. These are extremely difficult to treat in quite advanced, and then it depends really on the situation. Whether this is a bilateral or a unilateral case. For instance, if you have an advance too many Ryan, a unilateral case without family history, and they usually will present very late at that stage, so there's almost no hope to get any vision in that eye. And actually the best treatment for these would be.

To remove the eye in nucleation so the treatment is staged to the stage of the disease, we basically have three or four major groups of treatment. You have a local treatment. This means in the Group A or B you can destroy these tumors with a laser treatment, cryotherapy or breakey therapy. This localized radiotherapy you can use chemotherapy and there are three different types of chemotherapy and I come to that in more detail. Finally have radiotherapy. The breakey therapy are set for local disease only, but if you have advanced disease.

You can use a broad beam and an external beam radiotherapy, and finally you have any nucleation. As I said, this is still the standard treatment for very advanced disease, in particular in unilateral cases, so unilateral cases present usually quite late, so the eye is full of tumor in advanced in adverted commas. The other eyes fine has no problem. So with enucleation, with the surgical removal of the eye basically child is healed, there's no more disease you don't need anymore treatment, your other eyes OK.

And you have a very good chance of leading an absolutely normal life. So these are two children where I did the nucleation. You could see some years later you can see an enucleated. Either difference of an artificial eye by the movements and the little bit closer together but further apart. But usually these children leader completely normal life and it works much better than people think. Complications of enucleation's are covered in more detail in the adult talk, a vocal oncology, but the main thing to lookout for in particular children.

Is problems with the orbital implant that is usually buried under the conjunctiva. You could get an implant exposure as is shown here on the right hand side. So you need to lookout for that. If you have patients in your daily practice that had nucleation, it's always worth checking under the artificial eye to see if there are any problems with the orbital implant.

So let's move on to local disease Group A, Group B. These are tumors within the retina that haven't disseminated, and these are usually quite straightforward to treat. You have to destroy the tumor cells, and you can do that either with laser treatment with cryotherapy, or with breaky therapy with Indian plug. So with a laser you just go in and use the laser as a very very bright light basically, and ZAP the tumor way exactly like it is in this picture. That's how it works. With cryotherapy, you come from the outside.

You have a pen like cryoprobe that then will freeze the tip to minus 60 -- 80 degrees and that freezing will destroy the tumor cells and can do that through this Clara as well.

So this will be used. You can see a very very sort of pale tumor here in the retina. This is small rattling blastoma. This is a child that was a son of an affected bilateral retinoblastoma patient. So the patient you shared bilateral stoma.

The child was born on day one. This day. Pictures taken on day one after birth. You could see this a small tumor right next to the fovea and you get the you laser treatment and this over the years will develop a scar. But Fortunately the foveal was saved and the child had excellent vision in there. Diane, this is the fellow eye of the same child. You see small tumors next to the fovea treated with laser, and although this looks a bit brutal, actually the vision is an excellent because the full VR is still working really really nicely.

Moving onto ruthenium plaque radiotherapy. This is for slightly larger tumors that are too large for laser treatment, or cryotherapy, for example. A case like this, you cannot really laser that you can't get all the way to the deep tissue of the tumor to treat it with laser radiotherapy very localized with the plug is the treatment of choice and you can see our nicely this tumor reacted to the radiotherapy. It's gotta scarring information afterwards, but an excellent tumor response.

Now the other type of radiotherapy is external beam radiotherapy and this has been the mainstay for 3040 years really of the treatment and this can be used basically like a blunderbuss approach. You can see this is a setup of they children get about 2030 bouts of radiotherapy spread out over a month. They have to be put into general anesthesia for that left we fixed and you have to have a treatment plan and basically the whole eye in the orbit is radiated with that external beam radiotherapy.

It's been used for a long, long time and over the, let's say from the 1950s to the 1980s nineties, that was the number one treatment for disseminated disease that you could not treat with local measures like laser or cryotherapy and actually random blastoma and tumors that really respond well to the radiotherapy you can see here on your left. A very advanced tumor with vitreous dissemination and overtime. It's basically all breaking down. Everything's going away with the radiotherapy.

The same tumor on an MRI scan. You can see the tumor at the back of the eye on an MRI scan. Basically melting away under the radiotherapy. So regarding the efficacy to treat the tumor, this is a very very good tumor, but it has significant side effects. Unfortunately, number one is. If you radiate your eyes, it will have to radiate the orbit as well, and so if you radiate the bones at this stage of, let's say, one year of age or six months of age.

They will stop growing so these patients develop a facial deformity, hyperplasia, meaning that their midface is not growing in the way that the rest of the face is growing, and that can sometimes look really, really awkward and can be a big big burden on the patience. So this is a typical appearance of retinoblastoma patient that previously underwent radiotherapy, but that's not the main reason why this treatment basically has been abandoned by now it is.

A big big lesson we learned in Madson Becausw. Something terrible developed after the radiotherapy, but it developed many many years after the treatment. So what you see here in the red curve is the rate of secondary cancer in patients undergoing this type of treatment. There is a big difference in hereditary and nonhereditary randomness. Tomasso patients with the registry reference to mother have a gene defect that gives them a risk for developing cancers elsewhere. And if you have that risk.

In combination with the radiotherapy that out of a sudden increases your risk of developing a secondary cancer massively, but the problem is it took 30 years to find that out because it takes a long for the secondary cancer to develop. So what you can see for instance, at the age of 30. In these cases the patient there had a 30% risk of developing secondary cancer, so unfortunately a lot of the patients treated that way died.

At the age of 3040, fifty from secondary cancer following the treatment, whereas if they wouldn't have had that treatment, there would still be alive and not developed that secondary cancer. So that was a big big shocker and big lesson learned in medicine that you do need a long term follow-up. In particular, in Retamar stoma patients, and This is why about in the 1990s people when they realized this disaster really outcome that they looking for different types of treatment.

And this is where then chemotherapy came into the treatment of retinoblastoma. There are three types of chemotherapy, systemic intra, arterial or interventional. So which is which? While systemic chemotherapy is the usual chemotherapy, you know you get an infusion of a very strong drug that will kill all cells, develop quickly, so the cells that develop quickly. For instance, your hair cells, you lose them. Typical side effect of chemotherapy and cancer cells that grow quickly that will kill the cancer cells. In this cell, chemotherapy works.

You've gotten your blood cells develop quickly, and unfortunately these out another side effect of type of chemotherapy, but systemic chemotherapy is very effective in treating retinoblastoma, but it has quite a number of side effects. This is why the next development on the way was intraarterial chemotherapy. This is that you put a catheter into your bloodstream and tried to give the radio 30. Sorry, the chemotherapy only into the ophthalmic artery, so not systemically, but only very localized into the artery.

That gets the blood into the eye to have a higher concentration there, and finally the latest development on that front is in to even avoid that and just inject the chemotherapy straight into the IB cause most of the retina blastoma cells are within the eye, and then you have a high concentration of that chemotherapy.

So the first development really was the systemic chemotherapy. You can see the drugs here, and that was a game changer away from radiotherapy because written blastoma, cells usually respond quite well to this treatment. You would have six cycles of this chemotherapy. So imagine you got a 3 month old baby and it has to undergo 6 cycles of chemotherapy there. It is quite a burden, but the tumors responded very, very well to this type of treatment. You can see here from left to right.

Advanced Retina stole my big Wrecking Ball stole my India. I really crumbling down and scarifying after the treatment. Another example. Big big tomb at the post. Polio can't laser at you. Can't put a plaque on this. You external beam radiotherapy would pose you at the risk of developing secondary cancer with chemotherapy and the whole tumor melts away. So it's a really, really good treatment. For this you need to combine it with local therapies. Some heating of the tumor, so not direct laser coagulation.

Is usually used for this combination treatment.

So the outcome is measured basically and I preservation. So how many of these eyes can we save when we use chemotherapy and you can see in the smaller tumors it's very very good, but in the group D&E, 71% in 32%, so it's better than before. You can avoid enucleation in a number of patients, but it's not really what you want to get in these advanced retina blastoma.

The side effects of this type of treatment and complications usually very well tolerated, but you have transient problems with alopecia, neutropenia, and fever, nausea, MSS is the normal, very rare cases of infertility. Very rare cases of leukemia in combination with other treatments. Usually there usually is no ocular toxicity because the levels of chemotherapy in the eye are quite low and we've been doing this for 22 now almost 30 years.

And so far there has been no increase in the rate of secondary cancer, and of course that's a big big thing. Did we just switch the risk of radiotherapy to same risk with chemotherapy? Now we don't. There definitely is a lower rate of secondary cancer using systemic chemotherapy.

So the next development is the use of intra aterial chemotherapy. So you inject basically the drug. This is melphalan that's been used into an artery, and then the ophthalmic artery. And yeah, this is actually a new radiologist doing this, not ophthalmologist, so they go into your vein somewhere in your groin and push a catheter up into your atomic archery. You can see it on these pictures, and they use some die to localize where they are with the catheter, and then you get a big big dose of chemotherapy.

Into the atomic artery and the advantages he got a much higher concentration with less systemic side effects, and there are some absolutely amazing outcomes of this. If you look at the picture on your left, these eyes chockablock full with retinoblastoma. Nothing you can do. Usually you have to enucleate the eye. You can see overtime how the tumor melts away with this massive dose of local chemotherapy and only a Sky at the back of the eye. Unbelievable treatment results compared to what we've seen before.

And another case, big big intraocular tumor with local chemotherapy. You can see it regressing.

And looking again at the eye preservation rate. Very good in smaller tumors. Better but not ideal in the advanced humor so you can save more eyes, but not as many as you really like. You do have less complications than systemic chemotherapy, but you have some local problems if you should such a high dose of chemotherapy will not only.

Go into the eye, but they often make artery and its branches will then also go to the skin around it so you have an edema. And because you have such high doses of chemotherapy locali, some eyes are killed in adverted, commas by the chemotherapy. So the retina choroid sometimes do not survive this treatment, so you treat the tumor successfully. But basically you kill the vision as well. With these high doses of chemotherapy. So it's something that one could see in some patients.

Overall, one sort of I still need to be enucleated metastatic disease is low. So the question is do we risk lives by doing this and that's a big big discussion. Certainly in unilateral cases it's a big dilemma for patients in particular for the parents to decide you've got a child with a unilateral rotten blastoma. Advanced disease in one eye, the other eyes fine. The easiest thing to do is to enucleate the eye, but will my child asked me later in in 30 years? Did you really try everything to save my eye?

Why didn't you do this local kind of chemotherapy? These are really difficult questions, and it's a very difficult discussion with the parents about this. You do have local side effects run on the attachment rate is substantial and 23% is quite something, and this retinal choroidal is chemia. The biggest side effect on inside the eye is nothing you can do about that. Once the eye is gone, it's a 13%. You do have some hemorrhages inside the eye and the edema as saying before you can have some ocular motor policies, so this might be a patient.

That comes into your clinic with some mobility problems following local chemotherapy and you have a contract development, but on the plus side, almost no systemic side effects. And now after 10 years there is no sign of any increase of the rate of secondary cancer in this group of patients.

So moving on to the last group of chemotherapy. This is for the eyes as a set. About 30%. You can save the advance written was told more, but still you have the nuclear quite a number of eyes and this is where the last type of interpretable chemotherapy comes in. So this is a drug straight injected into the eye and one was very careful before 1. Does that why retinoblastoma is very aggressive in type of seating outside the eye. So there are some reports where people didn't know there was a written blastoma in the eye or didn't check.

And they've done cataract surgery and with opening the eye, basically you kill the patient, be 'cause there are seats of the tumor on the outside of the eye, and they go everywhere. And it's a disaster. So people were very, very hesitant to do anything inside the eye, including just giving an injection inside the eye, even if it's a chemotherapy agent. So these were the first developments you use a little injection now for us for adult treatment injections inside the eye are absolute routine. Nowadays this is a little bit more challenging. You have to put the child asleep, obviously.

And afterwards he usually use cryotherapy. You see that in the bottom left corner just any sales that might be seeding along the needle track that there killed straight away with the chemo author with the cryotherapy.

And again there are some eyes that do amazingly well with it. This type of treatment this I again full of tumor, but not only a big tumor, but it's like snowflakes everywhere in the vitreous in the vitreous doesn't have any blood vessels, so chemotherapy injected into the bloodstream doesn't really get into the vitreous, doesn't treat it, and this is where this injection treatment straight into the vitreous is a real advantage. You can see unbelievable results really in this tumor melting away. You've never seen that before, even with the systemic or intra arterial chemotherapy.

A little bit more differentiated, you see, and I hear from this publication with vitreous seats. I just highlight them in on the clinical picture as well as on the OC T. You can see these snowflakes really inside the eye before the treatment and with the injection treatment they're gone. So it is quite impressive what you can achieve with this type of treatment.

And the first publications from Japan really showed that you can control anything between 50 and 100% of the reported cases. And if we look at the eye preservation, this is where it's used. Now it's using to save eyes in Group DOE. So advanced cases with local dissemination that did not respond sufficiently to the other types of chemotherapy, and you can see you can really increase the preservation percentage up to 87% in Group D.

And 73% in Group E. But of course there are complications as well. One is really it's difficult to say how much is too much and it depends a little bit also where you inject it inside the eye, there's some channels in the vitreous. If you inject it in the vitreous, it's not too bad be injected into one of the channels. You may get a massively high concentration straight at the retina, and this is one of the published cases. You see a relatively small tumor in the popular macular bundle actually would say that could even be treated with laser treatment.

And unfortunately they developed a sum. That child developed some retinal complications. You kiss and see the hemorrhages and after some years you can see basically the choroid under the retina is gone. There is no retinal pigment epithelium in this area at all, and if there's no retinal pigment to be therium than the photo receptors don't work and you can't see anything there, so that's a major problem that hasn't been controlled 100%. In the treated cases.

And finally, quite advanced retina blastoma. We usually don't see this in central Europe. These are usually children coming from other countries, but you still now with a combination of chemotherapy and local surgery, can get a good result in even these advanced cases.

Of interest for you, probably in the Retina Stoma treatment is you should also do patching in these eyes. This is a macular tumor. You wouldn't expect much vision afterwards if you're treated, but with aggressive patching following the local treatment you can see a very nice response to the chemotherapy and laser treatment, but with patching it improved, so it may be that in the future you will have more and more regular stoma patients. You didn't see them before because the eyes usually were enucleated or had no vision at all.

But it may be that you will see more and more patients in your practice for some type of patching, treatment and umbrella prophylaxis after the treatment. So you can see here everything above the diagonal is an improvement in vision, and you can see with patching you can improve the vision in quite a significant number of cases.

So, in summary, regarding the management, what are the most common mistakes? This is the worst patients ever had in my life. It's a small boy, six months old with bilateral advanced ratable stoma and the mother had threatened by still more as well, but the family history wasn't clear and she never had any counseling for potential genetic disease and retina blastoma disease. So unfortunately I had to renew cleared both eyes of this little boy, but due to advance disease there was no intra arterial chemotherapy. And those days.

And a lot of cases are problematic in the work up, so I just want to summarize regarding the management of retinoblastoma patients. The number one is and these may be patients that come to you that local Korea is not properly investigated for. Mother comes and say she never says there's a wide pupil and they will say there's something like a little glitter in the IR. Little I don't know. Bit of light shining in there, so this is when they put the children into bed and they have low light.

And the pupil is wide. And then they see the retinoblastoma, whereas when they're in front of you, they got a small pupil, and you have no chance. So it's quite important that if the mother has any hint of their sort of like a shining pupil or something tells you that this is investigated properly.

And and you strap ISM is often underestimated, and this is where you come into play. So you have the normal strep ISM which is there from day one basically and never goes away. But the real emergency that you need to be aware of is a GNU strep. Isn't that a two or three year old child out of a sudden develops, a strap is, and that's always a sign of a serious eye disease. Most commonly is a cataract or retinal problem, but it can be read from Bristol Myers. Well, so any child coming with and used wrappers and no history of any strap ISM at all before.

Is a medical emergency that needs to be seen as soon as possible by an ophthalmologist.

People also underestimate that unilateral retinoblastoma can be hereditary in 15%. So if you got a patient with a 1 sided rotten bus told by nucleated year fine, don't think they don't have a risk of giving it to their offspring, so they need appropriate genetic counseling which is much improved nowadays.

And some patients, but never been told the correct diagnosis. I had a lot of retinoblastoma patiens where the eye was removed as a child and the parents told them because we're kind of ashamed or so difficult to understand. But they said, oh, you had an injury with a stick or whatever and that was it. So it's worth getting the medical history if possible. Spot on and to find out which patient had a rotten blastoma in which not.

A common differential diagnosis is this. The white retinal tumor. This is an astrocytoma. This is a benign tumor of the glial cells of the retina, and that usually only needs a photograph and observation, so no active management, like in this case close to the optic disc and no change overtime so we can go over this.

Cause we don't really have any active treatment for these cases, they are quite benign and don't cause any problems.

Now comma differential diagnosis for retinoblastoma is a retinal vascular disease called coats disease, so these are retinal vascular Taylor and get Asia. This means they have an inborn error of the retinal blood vessels, so you can see that in the top left corner these blood vessels look like little light bulbs and the problem is they leak fluid, so they're not as tight as a normal blood vessel in the retina which doesn't leak fluid. These ones are like rusty pipes in a leak fluid and indirectly you can see it by the yellow exodites surrounding it.

So you can see it also in the angiography underneath and any treatment there we have to stop these blood vessels from leaking and the easiest way of doing that is destroying them because they're usually on the side of the either not in the center of your retina, and then they're pretty straightforward to just clarify them, destroy them, and that will do the treatment.

So these are the errors at question there or we can see here the area question is out there in the periphery these are the codes blood vessels that a long react Asia and they can then cause these exodites more centrally. All of these little yellow bits you see there is caused by the leakage from the side, so sometimes it takes years to build up before the children get symptomatic and somebody can see anything. And that's sort of the advanced disease where the patient then presents because their vision will drop from 6626, sixty or so.

And then they develop a strong business and this is how they go to the doctor of four year old will never say I can't see anymore of one eye. The way to see it really is developing a new strap ISM in that. I know you can see all of this is caused by the blood vessels on the side and in the very advanced stages you will develop a total retinal attachment. And this is a very difficult, sometime distinguished from a rattling blastoma. So the eyes chockablock full of gunk in adverted commas from these.

Blood vessels you can see in the top corner there they leaked fluid under the retina for years and years and years, so this patient developed a total retinal detachment and the treatment is adjusted again to the stage. If it's very localized, it's pretty straightforward to destroy these blood vessels with laser. They form a Sky and stop leaking, but a little bit more. You can use cryotherapy and if it's advanced you need veteran or surgery. So just an example again here on the side of the eye you can see this area of quotes, blood vessels that caused.

The central oxidation there, so these are the markers for the executive retinopathy and all you need to do is destroy the blood vessels on the side. You can see here. This is the laser scar following treatment and you can see that the Exodus disappeared. We turned off the tap of these excitation and the vision is much better afterwards. And another case here. This central codes disease, lots of excitations, but actually this is not caused by anything at the center. This is really caused by.

Blood vessels on the periphery of the eye, and this is after treatment. You can see how this exodus it will go away after successful treatment, although in this case the vision won't be very good. You have to Patch it. But just to point out whether treatment really was, it was here on the side you can see the scars there over the laser and blood vessels. This is where the disease is.

And finally, you have a lot more advanced disease like this. The almost the whole retinal detachment with lots of extra dates. Again, this is caused by blood vessels on the side there in the periphery. These are the leaking blood vessels that will cause the red on the attachment and after laser treatment, the retina at least is attached again. But there will be no good vision in that eye.

Moving onto for nipple in no disease and these for the eye POV is retinal angiomas really so it's a relatively condition associated with humans in multiple organs so they can develop disease elsewhere. And it's very, very important that they undergo regular screening for all types of organs because this is something that can kill you by developing kidney cancer and other cancers. Whereas if you detect these cancers early, you can really save alive.

So what's happening in the retina? Is these patients from childhood onwards, teenage years early sort of adult life? They develop more and more and more retinal angiomas

so it's a continuous process and the patients need to be monitored lifelong for the development of these new angiomas. So these are not cancer cells inside the eye. They can develop cancer elsewhere, but there's still very, very complicated and nasty things because again, like the codes disease telangiectasia, these are angiomas that start leaking fluid when they're small in the retina, like this one, they don't cause any problems, but as soon as they get bigger they can start excitation leaking again.

Into the retina and in the advanced stages, just like coats disease, you get larger and larger angiomas with a retinal detachment. So just to show you some clinical pictures, this is a small to moderately sized angioma and you can see the blood vessels are bit dilated because there's a lot of blood to get to and from the angioma. This is more advanced the way you have some extra Dacian already and a little bit of retinal detachment. And finally it can really develop into very advanced disease with a retinal detachment.

And that I and this is very complicated to treat.

So they can really, really form and all kinds of aspects everywhere in the eye at the macula, at the disc, in the periphery, and they don't stop growing, so screening is really, really important, because in the advanced stages you can see it in the lower right corner. You will get a read on the attachment that is extremely difficult to treat.

So the treatment again is aim is to destroy an scarify. The angiomas, just like the vessels in coats, disease and advanced disease you see in the bottom right corner you need to do vitreoretinal surgery to treat the retinal detachment. The treatment options again depends on the stage of the disease. We do have local treatment with laser cryotherapy, bit more advanced. We can use our Athenian plugin proton beam radiotherapy.

And if you have retinal detachment, we need to use vitreoretinal surgery.

So starting with the easier cases, this is a very small angioma. You can see how you can pick that up by fundoscopy and all you need to do is just laser it and scarified. It won't cause any problem ever again.

This works well for medium sized angiomas like this one.

Again, laser treatment pretty straightforward.

These are some examples of patients that had multiple treatments in the left picture you see a new angioma and older angio mistreated. They develop more and more overtime, so every year you need to check on them to see if new Angiomas developed in the middle as well and to the right, some newly treated angiomas in multiple areas. It depends from patient to patient. They can develop one or two angiomas or they can develop 50 in one eye. It is not predictable for the patient. Once you have a more advanced disease.

Laser is not sufficient in this case, cryotherapy was able to destroy the angioma in the executive retinopathy.

And if it's even a little bit bigger than that, then it's ruthenium plaque radiotherapy. This is covered in greater detail in the adult of ocular onkologie talk, but basically it's a small radioactive disk that we suture onto the outside of the eye exactly where the angioma is. This will radiate onto the angioma and you can see here the scar developing around the angioma and angioma getting smaller and smaller overtime. It's an excellent treatment for localized disease.

The biggest problem of the small and medium sized angiomas we have is when they run the disk. You cannot use a plaque on the disk and if you laser or freeze this you will destroy nerve fiber cells as well. So the patient unfortunately does have a significant risk for developing visual field defects after the treatment. This is one that's been successfully lezard and you can see overtime how the angio must clarifies and we were lucky in that case because the tumor was sitting on top of the nerve fibers or the nerve fibers continued to work so there was no visual field defect.

But this can be a problem if the angiomas more localized inside the retina and not on top of the retina, like in this case an angioma on the disk with executive retinopathy and with proton beam radiotherapy. It doesn't really get smaller, but you can see the indirect effect of the treatment by the aggression of the oxidation. You can see the amount of excitation before treatment and then overtime with treatment less and less. So although the angiomas still there and looking quite aggressive, actually it's clarifying you can see that indirectly by turning off the tap.

Turning off the executive retinopathy.

And in very advanced disease you need to use multiple things. This patient presented with a hemorrhage from the angiomas inside the eye there was some scars of treated angiomas, but also we thought they were more angiomas. You then do an angiography and in these cases to see what's going on and this patient had 41 active angiomas you can see all these bright dots these angiol must filling with the dive from the angiography and you need to treat every single one in order to be successful.

And this is after many, many treatments in a year Ruthenian plug on the side of the eye. But all these models.

This had to be lazered and a good regression of the vitreous hemorrhage and the retinal detachment.

And this very advanced case, you can see some treatment has been done before, but unfortunately the patient developed a retinal attachment with scars in front of the retina and combination treatment of retract me laser Athenian plug and silicone oil tamponade. At least we could reattach the retina to save some vision for some years.

Now the next group of diseases of choroidal Hemangioma. This is a bin 9 congenital too many of the posterior pole, so patients are born with it, but it's not hereditary so you don't ever risk of passing that on to the next generation. We don't know why they develop in there almost always near the disk or any other macula, and they're often patients you may find so called amblyopia. Amblyopia means low vision with no explanation. Normal anatomy. This is not quite right in this case because they do have.

A Hemangioma meaning that they have a big lump in the macula or near the macula. So your vision will be poor, but it's sometimes very difficult to diagnose these hemangiomas because they looked like choroid, so there's small thickening of the choroid that sometimes it's difficult to detect.

They can stay silent forever, they're just there and that's it. In there cause any major problem but overtime they also can develop executive retinopathies. So leaking fluid again into the retina or under the retina and causing visual problems.

The management really is only indicated if you have a problem. So if you have a silent or long standing activity with low vision, we wouldn't do anything. We only get active if you have active executive retinopathy with visual loss and then the both treatments we have that are quite successful are photodynamic therapy, PDT, or radiotherapy.

Can see the angioma see at the posterior pole and there's other case here. An angioma under the macula, but you can also see this is so active and produced so much fluid that the patient actually developed a retinal detachment and exuded threaten attachment in feriale.

So PDT photodynamic therapy again. This is covered in greater detail in the adult management oculum cology talk, but basically what it is, you get an infusion of a drug that sensitive to light, so you infuse it into the body. The bloodstream will fill the Hemangioma and then you use delays as a light source so you don't ZAP the tumor, you just activate the.

Photodynamic process within the drug and that will Clock up the blood vessels within the Hemangioma and then hopefully reduce the activity of the human genome a like in this case. You can see the Hemangioma smaller but as proof of the effect of the treatment, although run, an attachment is gone, just with a photodynamic therapy.

And this actually was a child, a 6 year old child with a large Hemangioma. Unusual but still it has happened with quite a bit of executive activity that probably would have been too difficult to treat with PDT, so we treated it with ruthenium plug. An excellent response. So the tumor is clarified and the executive retinopathy is gone.

A complicated subgroup of choroidal Hemangioma are diffuse scrotal Hemangioma. This is in particular in patients with search Weber syndrome, so you may see these patients with a nevus flammeus of your face and a lot of these patients not only have these vascular deformations on the skin of the face, but they have them on the eye or in the brain in the meningeal as well. So if it's quite extensive, like in this case, you can see this patient also has vascular malformations.

In the lip and in the gums you can see the teeth and lips really coming forward. This is because everything's Hemangioma and they can get terrible eye problems, mainly because of a vascular malformation around the front of the eye that can lead to glaucoma. So very high pressure, very difficult to treat. So most of these patients were the nearest females when search Weber syndrome are in the glaucoma clinics in an eye clinic and not so much with us. But they can develop diffuse hemangiomas.

The back of the eye as well. You can see it here. Massive hemangiomas. Sometimes you can only see them on ultrasound, 'cause they look like normal choroid, but what you can see on the ultrasound here, the cord is massively thickened, and if it's quiet and silent or you don't need to do anything, but treatment is indicated. If they have additional visual loss exuded, threaten, attachment, or in advanced glaucoma just to lower the pressure inside the eye and treatment is pretty similar to what we've seen before we try a PDT in the first instance, you need to couple of PT cycles for that.

But you can see even in this very large diffuse Hemangioma, a very good response and complete regression of the lesion.

Finally, moving onto retinal VESA proliferative tumors, these are benign tumors that can affect children. Teenagers in most commonly seen in adults really there have been nine run on tumors not associated with any type of hereditary disease. Their spontaneous in about 70% of cases and 30%. They are secondary to other eye diseases. Retinitis pigmentosa, coats, disease, or longstanding retinal detachment or uveitis.

The problem is exactly the same as with the other angiomas and retinal vascular lesions. These are just blood vessels that leak a lot of fluid like you can see in this case. The tumor itself is down there, but look what it caused. It cause problems with the yellow executive retinopathy and an executive retinal detachment right next to it so they can cause quite a number of problems, but they usually located on the outside of the eye and the very periphery in particular in the inferior periphery. So problems is the executive activity in Maculopathy.

Small lesions sometimes can be observed, but we usually don't recommend that we use treatment. PDT is successful in a lot of these cases and you can use the others that you already seen. Destroy the blood vessels with laser cryo when advanced cases with ruthenium plaque radiotherapy.

So he is a problem. Sorry a patient with the eraser retinal vessel prolific tumor in the inferior periphery and you can see with the PDT if you look at the exodites again the yellow bits surrounding the tumor. This is our measure of success afterwards that humor doesn't go away, but we could reduce the executive activity.

If you can see this very advanced tumor that's been monitored for some years, we don't like that. But this patient didn't want any treatment out of a sudden, you can see how this little small tomb I see all these executive retinopathy there. It's caused by this little tumor down there so they can leak a lot of fluid under the retina. One PDT treatment only is enough to get rid of all the extra dates, but wherever you've got exodites under the retina, it's like burned earth and it will not recover. The patient will not see in this areas.

But there's a limit to what PDT can do. If it's too advanced, like in this case, the PDT would not be successful. We usually use our ruthenium plaque radiotherapy even for benign cases, sometimes difficult to understand, but you can use radiotherapy also for non cancerous disease. It's quite successful for treating angiomas and you always need to look at this case, for instance at the disk you can see that this patient is quite a bit of apparate membranes. This patient did not want any additional surgery to the membranes, just wanted the.

Rational basis proliferative tumor treated, but there are other cases like this. It doesn't look really much. You see that small basic relief of tumor in the inferior periphery. But if you look very, very carefully during your examination at the macular, there this is the tumor, and this is the macula area. There you can see a very thin scar over the macula, and oppression membrane, and the best way to detect that is an OC TX emanation, and you can see here that membrane on the retina, distorting the retina in the center.

So what you can do in these cases, you can just combine the peeling, the surgical removal of that membrane with a laser treatment an both in one goal. Basically with one surgery membrane removed, vision much, much better and the retinal basic proliferative tumor treated.

So I'd like to thank you for your attention and if you do have any questions regarding this talk, please contact me. Under this email address. Thank you very much and hope to do face to face teaching in the future soon. Thank you.