 Hi guys All right everyone knows me Right no blast over other ocular to that's what this is about, but Let's put your thinking cap on Good morning So look at some slides. I'm just going to show you some tumors Right, and then you tell me No, keep it to yourself. What do you think it is? Maybe has something to do with the title It's harder Now you got to pay attention. So this is this is what ocabs and powers is the first year and a half Here's it. Here's the first quiz Ocap-ish slide My army It's a second one. Oh, sorry It's a second different patient. This is this is what is it? There's number three Thank you when it gets this based on the photos far smarter than I am That's our right. So this is kind of what you know, Ocaps is like Which information actually zero give me zero throw out kids all of the kids So many of these you're not going to know the exact diagnosis But you should be able to come up with a differential some idea That one you should have the exact diagnosis there's pattern recognition of that one so We'll get back to those slides at the end and hopefully From this lecture you'll be able to figure out better The differential diagnosis for each of those clinical photos and even the diagnosis on some of them So first an overview of retinoblastoma update on treatment. I'll talk about genetic testing and Counseling we'll talk about an empiric risk Over of another kid having retinoblastoma when one kid's diagnosed with it and then we'll talk about the genetics behind that And that's pretty damn confusing Right it confuses everyone and so it's always thrown on the Ocaps So I'm going to try to prepare you for your Ocaps, but also help you understand clinically the complexity behind those difficult questions about What's the chance the next kid is going to have retinoblastoma seems to always come up And of course the family wants to know Retinoblastoma is the most common intraclare tumor of childhood. There's no race sex seasonal Predelection about 350 to 500 new cases per year in the United States as of a couple decades ago This is kind of interesting 90% don't 90% 9 out of 10 have no family history, but you know there's tons of genetics behind this, right? So I'm just going to ask this question. Just let this sit in your mind for those 9 out of 10 kids of no family history where those mutations coming from There's a mutation in the RB in one of the RB genes, right? So where's it coming from if there's no family history? So just think about that. Okay, just Hold that question in your mind because it's something we'll talk get to and most are unilateral and 70% unilateral about 30% bilateral look if they're bilateral they've got what's called a germline mutation, right? If they're unilateral they might they usually don't though 85% don't have a germline mutation We'll dive into the genetics leaders to understand that You know when retinoblastoma is heritable it's Inherited in the risk of it is inherited in an autosomal dominant fashion, but a tumor arises a Cellular level because two genes have a mutation so it's autosomal or excessive at the genetic level But the risk is inherited in an autosomal dominant fashion And then if you do inherit one of the RB alleles with a mutation the penetrance is 90% Okay, so 10% chance you won't get any tumors even if you do Look in Sudan and Africa with no health care you can die for from retinoblastoma the developed world. You almost can't I Mean there is some mortality supposedly in the Western world, but we find this and Generally cure it if it's untreated and undiagnosed though optic-nerving Corital invasion occur and ultimately extra ocular Look at that kid. Who's the most astute person in the room? Me because I've been doing this for 25 years But take a look at that kid, what do you see look at that kid? What do you see with that kid? Dive deep look at the Luccorean right okay, so that that pretty much any ophthalmologist look at that, right Look at the kids face is that face normal look at the filter look at the lips Look at the nose That's that's that filter was really long those lips turned down so this is a kid with a Chromosomal deletion spanning one of the RB alleles Does that make sense? So that's just just a little tip for you Okay, if you lose a big chunk of chromosome and what are the RB alleles is in that big chunk of chromosome? You'll get 90% penetrates at 90% chance of retinoblastoma, but in addition to that you'll have seizures Mental retardation abnormal face ease. That's what that kid has Usually though so how does this present? This kid actually presented with seizures to the ER and an ER doc picked up the Luccorean pretty cool Usually it's Luccorean that's seen and usually it's the parents who's always right every lecture. I say this come on Who's always right? Mom Mom's always right and so if mom sees something wrong with the pupil Mom's right sometimes dad but mom's almost always right and There are unusual presentations. They're like strabismus Because there's a macular tumor poor vision eyes starts wandering, right? and then late Late, you know advanced retinoblastoma like glaucoma Hypopia and hyphae that's pretty weird in the US. It's usually picked up before that and And how else does it present trilateral anyone ever heard of trilateral retinoblastoma? It's bilateral retinoblastoma with the pineal blastoma in the brain. It's horrible. It's fatal That that can happen with heritable retinoblastoma. Finally that's something like 35 cases ever reported in the literature of UVitis masquerade called diffuse infiltrating retinoblastoma with a median age of diagnosis above five years Five years. That's weird kids with retinoblastoma present the first two years of life, right? So but I'm sure dr. Vittala and Ackbar can touch on that too If it's bilateral usually by one year, it's diagnosed and it's unilateral usually by two years. It's diagnosed and Parents pick this up parents listen carefully to parents so These masses are starting the retina the obscure vessels. They're white sort of creamy white When they're Small they look like this when they get bigger. They fill the eye. That's what you're seeing On the opposite side there. That's just Vitria is full of tumor up against the lens Same thing here high mag photos. Okay, you're just looking at To get you oriented you're just looking at the edge of a tumor here the retinas down here and the tumors would It's a huge mass. Okay Look at the vessels. They're dilated their feeder vessels feeder vessels are dilated torturous with tumors Growing tumors, you know things that are more benign the vessels tend not to do that Imaging studies calcification calcification calcification, right? That diagnosis retina blastoma, although rarely codes disease can have some calcium so frustrating But calcification is the hallmark of the imaging studies and ultrasound and CT are the best ways to find it I want to stay away from Radiation these kids right? because if they have inherited a mutation in an RV allele in an RV gene and Every cell in their body's got it and they're at risk of non-ocular tumors Sarcomas melanomas and if you are a radiated part of the body, you're raising a risk of a second hit We also like to image the optic nerve to see if there's any I Don't think this is that important, but there's endophytic and exophytic growth patterns into the vitreous in the subretinal space Prognosis is a little different based on the nucleation. We're a new glee nucleating fewer fewer kids But that's what it looks like with the gross path, and then this is the histopath flexor winter steiner rosettes central lumen specific for our be This is what optic nerve invasion looks like Icky Icky Ick that means system a chemotherapy Here's corridor inflammation infiltration treatment advances Well Treatment or retinoblastoma. Where do I start the 20th century? You can remove an eye If there's zero visual potential And you can remove an eye and save a life and you're done press that a guy So that's not a bad thing, but we try to salvage eyes of course if we can and salvage as good a vision as we can Sometimes it's so advanced though that we just There's no visual potential at all flat ear g aphor and pupillary defect eye completely full of tumor and You know, that's it's a really nice treatment because it gets this I mean done no chemotherapy. No no Long prolonged course throwing radioactive flax external proton external beam radiation Intravascular and intro vitro chemotherapy. I mean, it's a long hard course if you try to salvage an eye So sometimes just removing the eye, but you got to prepare the parents. You know, it's really hard. I don't know Who is kids? I have kids. Do you have kids? I can't anyone. Yeah, no It's really hard. What's that? That's why they're not here So external beam radiotherapy has fallen out of favor, but we still use Accurate proton beam Radiation selectively for advanced retinoblastoma that is resistant to other treatments with radiation That's what the regression looks like so called cottage cheese regression And then another way to give radiation is is a plaque it's I'd I'm plaque. It's sewn external to the scleron left there for a certain number of hours to give specific dose of radiation it can be used for tumors that are Medium-sized that other treatments are not eradicating for example Intravascular chemotherapy shrink a tumor cryotherapy or laser and it's still recurring This is a nice treatment choice But it can't irradiate the entire vitreous cavity. So if there's diffuse vitreous seeding, it doesn't work the local treatments generally Like cryotherapy and laser for tiny tumors that works alone, but we usually don't diagnose this when the tumors are tiny And so they have to be shrunk with systemic chemotherapy to get them down to the size where these local treatments work And up with vitreous seeding you can't eradicate vitreous seeds with laser cry. Okay, so it's got to be local Circumst, circumscribe small or shrunk tumors I'll just touch on systemic chemotherapy Yeah, I'll just touch on the the risks of it. Neutropenia infection risk risk of induced inducing hematologic Lignancy down the road and these are the chemotherapeutic agents that are generally used So this is what tumor shrinkage and local treatment with laser looks like here's Baseline photo before treatment. This is after chemo and one laser Here's after more laser and finally, I think that's the last one finally. It's eradicated. Those are flat They were elevated Here Now it's flat. It's just scar So it works really nicely I look the phobias purpose preserves, you know, you can get 20-20 vision in these eyes Intravascular chemotherapy is It was it was it was just like The second coming of Christ, it was like we're 20 cases with Dr. Abramson in New York about I don't know 15 years ago And I was like, oh, this is fantastic We just put a catheter up there and squirt squirt and we just get the eye and then You know in the beginning it was great, but like all new therapies sooner or later complications tend to emerge Ocular ischemia started to emerge Which kind of makes sense, right? Who knows what ocular ischemic syndrome is Stenosis of the ophthalmic artery, right? How does that present a dying eye? If you will an eye starved of oxygen So it's the same kind of thing and some of these kids will have lost their eye to nucleation because of that complication But it definitely helps avoid Systemic exposure to the chemotherapeutic agents and the side effects like neutropenia infection risk and later malignancy And this is used for the you know the advanced retinoblastoma when you got to just shower the whole eye with chemo, right? That kind of makes sense So secondary primary tumors I mentioned if you inherit a mutation in one of the RB genes It's in every cell in your body right so you can get non ocular tumors and Yeah, I won't dive too deep into these numbers, but You know a 30-year cumulative incidence Without radiation is pretty high. We're talking like a 1% per year per year risk and it's cumulative over time Right so 30% risk over 30 years without any radiation if you get a Radiation to treat the retinoblastoma then that risk is greater than 1% per year cumulative so we try to avoid radiation and Surveillance is really important and really driving home to the families that another cancer could be coming One in three chance in the next 30 years and they're bad ones Okay, so Poor forage Let me back up. I'll talk about the molecular genetics of retinoblastoma in a moment But let me let me do the OCAP questions here here here the OCAP questions and Parents want to know this too so to parents their first child Parents have never heard of retinoblastoma. There's no one in the family with any kind of childhood cancer Let alone my cancer and their baby has bilateral retinoblastoma and They at the end of the visit they look up and say I'm pregnant What what's the chance that my second child has this? What's the empiric risk? What's the correct number? The empiric risk at that point, you don't know anything about This fit the mom's genetics the dad's genetics. You have no genetic testing. Just what's the empiric risk? It's a little bit lower. Oh 100% of the thoughts. Yes. Yes a five six percent now. How long God's green earth? Because it's it's fine. If they have I Yeah, well, we don't know that they're normal. I guess right. Oh, I guess I was assuming what the mom had wanted No, we want to know that So really happy you guys are discussing this because that is Great thinking because you're thinking about autosomal dominance inheritance and autosomal recessive inheritance, right? But you remember the beginning of the lecture I said where are these mutations come from? Okay, where are they coming from so here's two parents binding their own business having a baby? It's got bilateral retinoblastoma in mom's pregnant Ask the question. Where did the mutation come from in that first child and there are lots of ways that baby can get the mutation Okay, and I'm going to dive into that in a moment and just You know bear the uncertainty of not knowing why it's 6% right now. I'm going to get there, but it's 6% Bizarre you think it'd be much higher Right, but but it's 6% and I'm going to go into that now Let me do it differently. Okay different family Parents are completely nor they've never heard of retinoblastoma They have a baby and it's unilateral retinoblastoma not bilateral But unilateral retinoblastoma and mom has a dry mouth and says I'm pregnant What's the chance that my next child has retinoblastoma and the empiric risk? Is it about you guys know it? Do you want me to say it? Yeah, like one one to two percent. Okay, so it's really low So why so damn low when when the risk is inherited in an autosomal dominant fashion well, I'm going to tell you okay First let's understand the molecular genetics There are two RB genes at that locus Unlucky chromosome number 13. That's how I like to teach it's unlucky chromosome number 13 So maybe I remember which chromosome And the protein is not of course it's involved with a cell regulation differentiation and growth. Okay, and both genes paternal maternal must have a mutation in a single cell for that single cell to turn into a cancer with uncontrolled cell division Okay, so at the molecular genetic level that's a key point both Both genes have to have a mutation This is what it looks like And and how can how can it happen? How can you get Both genes with a mutation paternal maternal what can happen? By random chance in both genes by random chance that can happen at both genes during normal mitosis in retinoblast division Okay, and So Here's a normal gene maternal paternal over time. There's a cell division There's a mutation in one of the two genes and then a deletion in a chromosome with a second mitotic cell division and that single cell turns into a retinoblastoma But every other cell in the body of that baby does not have a mutation in either Of the two RB genes, right? So there's no genetic risk that the next kid is going to have retinoblastoma And there's no genetic risk that that child's offspring will have retinoblastoma. Okay, and that's how most retinoblastomas arise The the heritable type of retinoblastoma though, there's an inherited germline mutation in one gene and then during mitosis of retinoblast the second gene gets deleted or mutated and Not surprisingly This process can happen more than once if every retinoblast in the developing eyes of a baby Has the first gene mutated There's a greater chance that there'll be a second mutation in more than one cell in the eyes And so you get multiple tumors and bilateral retinoblastoma Does that make sense? Okay, so There are all kinds of different mutations And it always takes two mutations and I just described non heritable retinoblastoma Okay, it always takes two hits both genes have to be mutated It just this happens by random chance because of the number of mitotic cell divisions during retinoblast or retinal development So you understand the molecular genetics and that at a genetic level this has to be both genes Autosomal recessive in a cell for the cell to become a tumor, right? well with heritable retinoblastoma The empiric risk you're right Brad 6% right Where do those heritable genes come from well the first take can occur in three ways One it could be inherited Because of a mutation during meiosis in the production of eggs or sperm Right, so there's a single bad sperm and by God even though there are how many millions of sperm, you know Trying to fertilize an egg that bad one doesn't But all the other sperm are normal In that ejaculate and and there's no mutation in the gammy in Gonad Okay, so the dad's totally normal genetically. It's just random chance mutation during comedogenesis So there's a single sperm, right? So that's one way you get a heritable mutation The second way there's a germline mutation in a parent So the gonads have a mutation in every cell and every sperm every egg is It's gonna have it, right I Apologize most of them and finally Another way to rise is is during embryo genesis Okay, so fertilization has occurred embryo genesis trucks along their cell divisions and by random chance One of the two retinoblastoma genes has a mutation and all cells downstream From that event during embryo genesis have the mutation and the other cells don't and That's called genetic mosaicism Does that make sense? Okay, and then there's a second hit that that happens during mitosis Like I said before and You have usually bilateral retinoblastoma multiple tumors. Okay, so the empiric risk is 6% Why well a lot of that that first kid remember here the parents. I'm pregnant our child That's bilateral retinoblastoma. What's this new baby's risk 6% why so low? Here's why Here's why mutations arise during a metagenesis Leaving behind everything normal in the data or the or the mob's gonads, right? Everything else is normal there or during embryogenesis and Everything prior to that mutation downstream from conception is normal So their next baby in those instances has a zero risk of retinoblastoma zero Okay But the empiric risk is 6% because it could be this presence of a germline mutation in an affected parent Usually the parent has retinoblastoma right 90% penetrance but there's a 10% non-penetrance and Immune surveillance can eradicate tumors in a parent who has a germline mutation and they didn't even know they ever had it So that's why we look at the retina of parents if we have a child with bilateral retinoblastoma looking for tumors That arrested because of immune surveillance looking for you know a regressed tumor So does that make sense? So it's just taking the average basically of all the risks, right? Yep Right, so let's get Yes You hit it right in the head so this situation is not common Germline mutation in a parent and the parent doesn't know about it. That's really uncommon What's common is a mutation arising during comedogenesis and a mutation arising during embryogenesis. That's common Exactly So it's yeah, right and you're that's way to go because just taking that 6% number you're like Oh, they have to be more common or it'd be 25% or 40% right? Yeah, so you got it. You cracked the code on this I'm happy you you're saying that So that's that's all I'll say right now about retinoblastoma But I just want to say this question in my experience always seems to come up on OCAPs and the boards and I want you guys to understand that this is in Retinoblastoma is inherited in an autosomal dominant fashion, but the empiric risk is just like has nothing to do with that The empiric risk has to do with how you get that Heritable mutation in the first place comedogenesis, embryogenesis or non-penetrant carrier the parent okay, and In this lecture, I don't really plan to dive into genetic testing, but not surprisingly once molecular genetic testing Became reliable. Oh, that's fantastic for us because we can tell the parents well There's a 6% risk. They're like, thanks No, I just have to wait and see Right. That's not really great answer But we have genetic testing though. So what we do the genetic testing so cool is we take either tumor after nucleation or White blood cells In this first baby with retinoblastoma and we find out the mutations We find out if it's a missense mutation and deletion whatever it is Then we know the two mutations and then draw blood from the parents Right and we can tell the parents In your white blood cells, you don't have the mutation. So what does that tell us? that tells us a lot It tells us a lot. It tells us that The gonads don't have the mutation Right if the white blood cells don't have the mutation the gonads can right Except one little detail Oh Well done. Well done. Yeah You guys are great. You're right. You can't be a gonadal mosaic You can't you can't be a mosaic where that mutation that testing of the white blood cells is negative But you do have it down here. You're going in. So you're right. And so when that Pregnancy when that kid is born one of the first things we do is draw blood and test for the mutation And if the white blood cells in that second baby does not have the mutation it's over The kids at zero risk Because even if that one of the parents has gonadal mosaic system the gammy didn't have the mutation or the kid would Does that make sense? so it's pretty complex a genetic testing but super exciting for us because We can stop doing UA's and the second kid We don't have to throw all the same as the Asian time energy and money At the second kid. All right, so let's move on Hopefully I've enlightened you a bit Not just oh memorize 6% memorize 1% Coats disease grapes Got me grapes It's a funny joke that I tell kids that maybe later. I'll tell you Tele-injectitious, right? I'll injectages. That's the hallmark of Coates disease the vessels are leaky There's actually a date So much exited it can be massive and look like a mass right It's idiopathic not a graduate 80% of cases unilateral Males get it more And the treatments are local Heat and cold this one Persistent fetal vasculature What's going on with this? Well, first, what is it you see when it's anterior you'll see fibro vascular plaque. That's retro lentil It can be thin like this one. It can be very thick The membrane attaches to ciliary processes and tends to elongate them and draw them centrally They're micro-ephthalmic eyes a highly artery can be present and Why does this happen? What's the pathophysiology? well There's there are multiple developmental genes turning on and off during development of the eye and Mutations in those genes during somatic cell divisions probably caused this The highlight artery is supposed to disappear, right? Well, it doesn't in these kids and the eye should be a normal size, but it but it isn't these kids It's micro-ephthalmic. So there's an arrest in development and if the rest in development is late during development of the eye you get anterior persistent fetal vasculature with this plaque And we can get pretty good visual outcomes in some cases by doing surgery removing the plaque removing the lens Optical optical rehabilitation and occlusion but Sometimes the retina is affected sometimes the mutation occurs pretty early in development And there's the mysterious photo Remember I said if anyone knows what that is they're way smarter than I am This is what it looks like. This is retinal detachment with this stalk the same thing here Same thing here. It's the whole retina can be detached It's when it's more severe posterior persistent fetal vasculature This one it's got a story behind it that I'll tell later, but only if you guys are curious Chirpy Flat demarcated lesion Isolated no big deal, but if it's multiple bilateral you have to think about Gardner syndrome Hey save a life with an eye exam, right? Save a life with an eye exam Familial adenosis, what is it polyposis? Help me help Familial adenosis polyposis is that it I got it and So it's a big deal, you know, they need screening colonoscopies and save a life with an eye exam. That's what I say Here's what it looks like. There's one isolated chirpy by the way, there's a cordial nevus kind of fuzzy edges Just for comparison in so-called bear tracks when they're multiple Bellino Cytoma of the optic nerve dark Benign pigmented tumor adjacent to the nerve. There's a little growth potential a couple more Estercitic hammer Tomas How do you describe those? How are those described? I don't know Metallic well circumscribed elevated you see any feeder vessels I don't see any feeder vessels, right? And you know what a mass that big if it's retinoblastoma, it's gonna be So if you see this photo you go On your your boards or you look at a kid in the clinic. Oh, is that retinoblastoma? No feeder vessels. Yeah iris lesions Lish nodules well circumscribe little mushrooms with neurofibromatosis, right helps us make the diagnosis Kids with neurofibromatosis As they get older Eventually they develop Lish nodules Early like toddler years. It's like one in ten As I get old kids have Lish nodules as they get older like five six. It's about One and four by the time they're 12 13. It's very high 80 percent 90 percent have Lish nodules So we get referred kids with cafe LA spots all the time asking us are there any Lish nodules? Because the diagnosis of neurofibromatosis type one at least type one neurofibromatosis is clinical and it depends on Cafe LA spots and how many you have a little freckling Lish nodules optic pathway glioma And so we're we're asked to look here. It is here's the prevalence Goes up like that. That's Lish nodules. Okay, so it's just a matter of time before you get them if you have type one neurofibromatosis There's a suspicion of neurofibromatosis So kids usually With no family history of neurofibromatosis have multiple cafe LA spots And that's when the screening gets rolling Do you ask them to wait until I say three or four otherwise? It's like low utility or you're like whenever The geneticists have a soak early Yeah, and in little kids, you don't have to use a slow lab You can use a 20 doctor lens and get in close with the indirect you get pretty good magnification And if you sing songs and tell stories and make gorilla noises sometimes though So you examine them Jxg anyone ever seen this? Anyone ever seen this? spontaneous high female Right That's sort of the OCAP teaching point spontaneous high female. This is in the differential like in a child in particular This is in the different differential diagnosis Here's here's a very big one on the iris and here here's the skin lesion Little more sinister That's a little epithelium, huh? How many have I seen in my career? Pretty much, you know, right? So it's pretty rare I've been doing it 20 plus years so pretty unusual, but It's Origin is the non pigmented epithelium of the ciliary body Iris mass in the first decade and really there is a spectrum of aggressiveness where some are fast growing aggressive others are very slow growing Nucleation is curative, but also local therapies with resection and the shields are doing Resection cryo couple other local treatments. I can't remember what else but in any case it's you know, its presentation is pretty pretty pleomorphic Here it is It's sort of a whitish Flat retro irritable Growth here is just a circumscribed circumscribed iris mass. Here's the one I saw very unusual This mass right here with high FEMA. It grew quickly. This is an aggressive one I wasn't sure what this was but ultimately ultimately the past show that's a little epithelium of that I was enucleated Okay back to the quiz We're wrapping it up now So what does this look like? Two masses high full of tumor creamy yellow Red nublastoma, right? What do you think this is? Yeah, why? Absolute so this like if I saw that in the clinic and someone said what is that say? Toxic crisis Brett nublastoma I'll call trauma with an intraocular wound foreign body I mean I couldn't there's just no way of knowing what that is, but the CT shows us calcium So it's right nublastoma This one? Yeah, why coats? What do you see? What do you see here? What are these little things? What are they called? On the vessels Tell injectages my craniosomes. What do they do? They're leaking right there's exudate in the retina This one that's the hard one Yeah, that's the hard one. So this is another one. Well, let me tell you the whole story because it's it taught me something So this kid Could this be retinoblastoma look at this elevated area and these vessels don't look dilated But you don't want to miss a cancer, right? So that's kind of uncertain and What else could this be? Yeah Right yes The other eye was normal So now I'll give you more clinical information, but you're right fewer anything else you can pretty much say anything and I'd say yeah Any other fractional retinal detachment? Yeah, right? Why would that occur like ROP? Which is I think of fever and ROP is sort of like cousins Sort of like cousins once genetic ones for prematurity, but they'll they both end up with detached retinas And what happened with this kid is that? He didn't have calcium The eye was the axial length was slightly smaller on that side And And I thought This is bigger than I am and I referred him to Abramson in New York kid at a flat air gene and They recommended a nucleation Because they they said it was uncertain that that Still had a chance of being RB Then they went to the shields Got another opinion and they said the same thing flat air G no visual potential still some risk of retinoblastoma So explain to the family That The risk of retinoblastoma was low, but we can't rule it out There's really no safe way to do a biopsy you can't biopsy retinoblastoma You drag tumor cells out of the eye and inoculate the kid and the kid needs chemotherapy at that point, right? So you're sort of faced up so I prepared the family so we we have to prepare psychologically that we remove the eye and It's not cancer We have to prepare for that psychologically ahead of time And I really drove that point home with two second opinions from experts We removed the eye and it was persistent fetovascular and the family was relieved it wasn't cancer But they also said we never would remove that if we'd known it was cancer. I can't believe we did not And so it's so hard for us to get our head around this stuff. It's so hard And but they all lived happily ever after it was it was behind them and the kid got a prosthesis and I still see that kid occasionally This one right why does it why do you why is it just tell me the clinical features Membrane right on and these are small eyes will be micro-pathomic the cordial be smaller on that side usually in the clinic And then when you if you do an ultrasound, you'll see the axial length the shorter this one Yeah, why why Yeah, there's no no feeder vessels in the tumor that size. Yeah, there would be feeder vessels this one. I didn't talk about this one differential this is a this is look at the date of birth 124 2011 image John 5 27 2011. That's a baby That's I'll just I'll just tell you because I didn't talk about the lecture. It's an irisempithelial cyst This one though Right right look. It's kind of a mass right the reason I threw this in is that these are fluid filled cysts So that's not much a lot of the oil. I think that's it. Oh, no one more Right on front it. Okay Is that the one where they have like absence of the crypts or is that just because it's a baby? No, not that I know The other questions that's good. Okay. All right