 but I'm going to get started because I want to get through a lot and I thought about cutting this and I apologize if it's too much material but I thought most of it were pictures so I thought it would be okay and I enjoyed it. So first I want to it's it's almost November right and so I just want to take a moment to thank you all for taking good care of my patients. Sometimes we forget to do that and it's so important to me when you're on call that you do what's important so that the patient does the best and I know you do so I want to thank you. So having said that I'm going to try to go through now ROP, X-linked retinoschesis, just some of the things in pediatric retina many of the conditions are really rare and so we don't see them very often. These are the more common ones, post-disease, familial, age-dated vitro retinopathy and just a little bit on non-accidental trauma. So I know you I assume you get a lot on ROP through pediatric ophthalmology too so I'll kind of go through this a little bit quickly but what I want to do is ROP is constantly evolving as we're able to save ever smaller and younger premature infants so I wanted to sort of bring it into light into the modern day in the United States so preterm birth in the U.S. accounts for about 11 to 12% of all live births so it's pretty common it's amazing that it's that common and ROP is a leading cause of childhood blindness it's about 14% in the U.S. but it can be up to 20% and even higher in some of the developing nations. So the developing nations that may lack some of the resources necessary to for perinatal and prenatal care so the maternal nutrition is important also oxygen regulation and it's not even whether or not they have ventilators it has to be like do they have respiratory therapists who can make sure that the ventilator settings are right so all these kinds of things play into it and we've really gone from preventing stage 5 ROP and treating severe ROP to really looking at ways to prevent severe ROP and to optimize visual function and on the right it's stage 5 ROP that's what we used to say we want to prevent that so it looks like a cataract but it's actually scar behind the lens the lens is clear and there's a total retinal detachment so we want to prevent that from happening but what's what's interesting about treating severe ROP and thinking about that is if we look at the early treatment ROP study which looked at earlier treatment with laser for severe ROP that what they considered successful those infants who had treatment and didn't go on to retinal detachment 25% of treated infants had 20 60 or worse vision at six years so that they're visually impaired now their vision may continue to improve but there there's also high myopia is true business so clearly there's a lot of room to improve what we do in ROP treatment and the the infants who had severe ROP but were not treated were randomized to not treatment so in an early treatment ROP study the threshold was a 15 about 1 5% risk of a bad outcome so when you think about it 85% of kids will probably do all right without treatment those kids who naturally regressed had better vision so you know maybe it's a laser treatment that's a problem so we have to understand how to prevent severe ROP improved visual outcomes the other thing that we need to be aware of is that ROP and the degree of prematurity are highly aligned and there are associations with extreme prematurity and low cognitive function and low neural development in infants and there's more and more work and research being done in this understanding of the neurovascular effects that occur in ROP I mean when you think about it the retina has so many cell types and we talk about angiogenesis but we have the effects of the glial mular cells on endothelial cells and the neural cells and the different ligand receptor interactions so these are other areas that we're going to hear more about ways to improve neural development ways to thereby potentially prevent severe ROP and these are areas where all of us are doing research currently so historically because we all of here about oxygen in ROP and I just want to lend give you some context about this so ROP was first described in premature infants but in 36 week gestational age you know now 23 week 24 week gestational age infants are living and they had no idea what it's from I mean they just started incubators they didn't have ways to really monitor the temperature they you know that in the infants have a different way of cooling themselves and heating themselves they haven't matured into adults the way we do it so there were a lot of things that the new incubators didn't do they didn't regulate oxygen very well and so there was there was a flurry of there were flurry studies done to recreate the incubator setting in animal models and a lot of these animal models were not premature but they develop retinal vasculature after birth or or they were affected by high oxygen at birth so like for example kittens exposed to 80% oxygen had this vaso obliteration and vasoconstriction followed by vasoproliferation and so people often talk about those two phases vaso obliteration vasoproliferation they're really the phases are based on animal models they're not really based on human ROP because the ability to see the retinas then it wasn't universally where we screened infants there was no indirect ophthalmoscopy knows it was hard to see the peripheral retina if you had a small pupil it would be difficult so it was then Arnold Patz really did the first clinical trial where he exposed infant or he he looked at two groups of infants normal versus high oxygen at birth and found that high oxygen caused retrolectal fibroplasia ROP then efforts were made to reduce oxygen levels virtually obliterated ROP but there was increased problems with neurodevelopment so it's too low oxygen wasn't good either and then a number fast forward a lot of advances in neonatal care extremely low gestational age infants less than 28 weeks or low birth extremely low birth weight less than 1,000 grams started to be saved and then we found that stresses behind besides high oxygen at birth would increase ROP so there are some studies that say high supplemental oxygen increases ROP I think it probably does and oxygen fluctuations also just the fact that the infants you know every time they try to adjust the ventilator settings the nurses do the infants have a fluctuation in their oxygenation so we don't really know everything that does but there are many stresses that that cause ROP and so like our lab is interested in understanding what some of those stresses what effects they have long downstream on ROP using various models the studies have not yielded clear guidelines as to what the oxygen saturation targets should be because a large-scale multi-center clinical trials have found that low oxygen saturation targets are associated with low ROP but they also are associated with increased mortality and there's a lot of variability in the different sites so just keep your ears peeled we just don't have the answer yet and other stresses have also been looked at so we really have revisited this this phase phases when we think about human ROP and we think more of phase one as really a delay in physiologic retinal vascular development you know when you look at infants with ROP you see that the vessels do not extend all the way to the peripheral retina and then in phase two there's a vaso oops sorry vaso proliferation and then there's actually a third phase in human ROP and that's a spibro vascular phase where you develop retinal detachment either partial retinal detachment stage four or total retinal detachment stage five so here are some images from a ret cam in a human infant and you can see on the upper left there's just the hint of a line in the periphery with a vascular retina in the upper outer area that's stage one when that line starts to gain volume and thickness becomes stage two stage three there's area of extra retinal vascularization stage four retinal detachment and I've kind of put down where I think of phase one on the left-hand side phase two is the upper right and phase three would be the bottom low or bottom lower right panel so you know whenever I think of a disease I like to think of prevention treatment of the acute disease and then rehabilitation and that pretty much follows every disease we know right so how do we prevent our people you know there are things that are being looked at there was a recent study a phase two study on IGF one which did not find an effect on ROP but of course it's a phase two so it wasn't really looking for that isn't a definite outcome but IGF one is being looked at ways to promote vascularization in peripheral retina but there are also ways like how do we prevent premature birth and I know we're ophthalmologists but there are things that we can be aware of you know we can always advocate for good prenatal care you know if we know there are various ways we can just in the way we conduct ourselves in day-to-day life and then the acute treatment would be screening the infants with indirect ophthalmoscopy or now fundus images and I'll go over some of the studies with that we want to inhibit basal proliferation improve vascularization of the a vascular and intervene at the right time point in progressive stage for ROP and then visual rehabilitation would be treating the what is known to be more common and premature infants with severe ROP and that's myopia and strabismus so general considerations of pre-maturity maternal infections chronic disease maternal obesity teen birth multiple births maternal drug use these are the things that we know are associated with premature birth the causes of premature birth are still not completely known the screening recommendations a lot of these I'm going to go over quickly but they're in your book and you had you had an assignment that's what the the quiz is based on what you were to read and I'm going to try to go over a little bit of that but mostly new stuff so this symptoms or signs of ROP there are none right so what we have to do is screen infants and in the US we are the recommendations are to screen infants less than or equal to 1500 grams or less than or equal to 30 weeks gestational age and to start screening examinations at 31 weeks PGA post gestational age so post gestational age is gestational age plus chronologic age and that's some or four to six weeks chronological age does that make sense I mean if you have questions you can just stop me because I know I'm but in other words if you have a 24-week gestational age baby at four weeks of age that they would be 28 post gestational age and then we always try to have the first exam before discharge because once the mothers and fathers and the infant who has all these other morbidities gets out if they haven't sort of been established with the eye doctor they they could get lost and we want to prevent that and then usually two examinations are needed to say that the retinas have vascularized to the aura and before we say there's no worry of ROP and once vascularization is complete to the aura serata then pretty much the risk of ROP is gone and these are also in your book this kind of varies depending on who you happen to be seeing babies with I think I generally see every week if there's any ROP and if it's in zone one on the first exam or zone two I I will maybe go to two weeks as long as there's no evidence of plus disease or ROP postmenstrual age is also used and I I prefer post gestational age they're sort of synonymous but the problem is that I will know that we really ever know postmenstrual age that's so it's gestational age and chronologic age in weeks and the thing to remember this is so one of the things really really really important is that when when somebody says oh I've got a I've got a baby who's was born 24 weeks gestation 900 grams birth weight and they have plus disease well you want to know what their post gestational age is because the PGA course correlates or corresponds very closely or pretty closely to threshold or severe ROP regardless of when they were born or the birth weight so that's a better that's a better indicator of risk of severe ROP so for example if I have somebody who's 40 weeks gestation 40 weeks post gestational age and they say oh I see a little bit of plus disease out when I see the baby I'm thinking you know they're probably winding down maybe they had plus disease before that was missed I checked the chart to see maybe they missed examinations because it were sick there could be a lot of things going on that baby I'm not as worried about is going on to develop type 1 ROP but if they're 33 weeks then I'm really concerned because the PGA for type 1 ROP and we'll go to that too is about 35 weeks post gestational age and for threshold was about 37 so threshold is more severe we really don't even talk about it anymore but I have a slide that you can kind of go over to see what the differences were and a lot of these are historic you know based on previous clinical trials so cessation of screening this is becoming more problematic now that people use anti-vegeta instead of laser because anti-vegeta can the the recurrences can occur 45 to 55 weeks post gestational age on average one one large probably one of the largest studies currently found that whereas in in infants who had no ROP it's usually like they're usually at 45 weeks and never stage 3 they're probably fine to stop the screening so it's really changed anti-vegeta has changed how we need to approach ROP and there was at least one case report of an infant who is two and a half years old we had recurrent disease so we're still learning we still don't really know this any of the specifics and if there is type 1 or threshold disease the recommendation now is kind of to try to get treatment in 48 hours so many of the clinical trials you 72 based on the historic but I think we're better off if we try to treat so you that as many you know I don't know how many of you have do you go wrong with like the pediatric ophthalmologist so that's why I'm always like wanting to get a heads up if there's a baby that we need to be worried about you know what happens is I get you we have a type 1 baby so the diagnosis is made and I have two days to try to get treatment but if they can give me sort of this is a type 2 baby that might be a little bit close to being type 1 then I can go see him and sort of figure out and you know kind of help the nurses know when you know we might have to treat next Tuesday I'll come by Monday if they're if they need treatment we'll get everything set up for that but if they don't we'll just continue so here are the parameters and ROP classification the zone the stage plus disease and extent of stage and the extent of stage becomes important when we're thinking about progressive stage for ROP which is retinal detachment so the zones here are the zone zone one is center they're all centered around the optic nerve except zone three and zone one is twice the distance between the optic nerve and where the fovea should be so it that's what the radius is and we don't really know what the fovea is in these infants so we had we sort of estimate and a way a good way to do it is use a 28 diopter lens get an image of the eye when you're looking into the baby and center the optic nerve in the center of your image and that any any vessels that don't go beyond that it's considered a zone one eye so there's a lot of variability of zone one right you can have some babies they have 12 clock hours that are all within that image others where it's only one and there are probably differences there are differences in the severity of those cases but we don't really distinguish that the stages I've already shown you stage one two three and then stage four with a partial retinal detachment plus disease is a certain level of vascular tortuosity and dilation and we talk about quadrants of involvement in type 1 ROP you just need two quadrants whereas the old threshold disease it was four quadrants and here's an image of plus disease word there's more work being done to try to quantify plus disease so it's not just a qualitative you know guess or trying to remember an image in your head a little bit on aggressive posterior ROP so this is often seen in the first or second examination and the baby may have it doesn't progress through the typical stages of stage one stage two stage three what happens is you see a baby very posterior disease often zone one or posture zone two dilation of the retinal veins tortuosity of the arterioles and then they can have what is known as flat knee vascularization so it it shows a little bit you can see over here it just looks hazy and there's maybe a little bit of a line there but it just gives you a sense of a brush on top of the rent that's stage three the thing that's interesting about aggressive posterior ROP is that may when we treat with laser we treat up to the vascularized retina may be difficult to tell where that flat knee vascularization is so you tend not to treat it also there's a greater risk of hemorrhage if you treat it but expect that once that regresses you're going to get reactivation in in between the junction of the vasculin and vascular redness so that baby will need additional treatment and I usually tell parents this that we stage it that this is to be expected and then stage five ROP again the same picture because we really don't like to see this so I use the same picture over and over and it can and if you look in cross section the retinal detachment could be all different kinds and all different configurations and the one on the upper left is kind of considered an open funnel it's a lot easier to treat and well it's not easier but it has better outcomes whereas if you have a tight tight funnel it's a one on the bottom it's hard to treat you cannot when you operate on these kids you cannot get a hole in the retina so it's not like an adult retina where you flatten the retina put a hole in the retina drain subrenal fluid put laser that won't work in kids they'll just end up with severe PBR so what we do is we have to release the traction we often stage the procedures and over time the retina settles back and time can be months we expect that so I'll show you some pictures of that in just a little bit so let's go so any questions it's sometimes hard for me to give this talk because there's there's so much and I try to figure out what would be the best way to present it to get a lot of information across in an organized fashion so if you do have questions so there are various ways that we screen our LP the indirect ophthalmoscopy and now wide-angle imaging like we use with the retina right so the pros with indirect ophthalmoscopy it's considered gold standard by many it allows you to see the auricirata concerns as it requires translation from viewings to retinal drawing so you know the baby's moving and you're getting these images and you're trying to piece them together and figure out as you look all the way around the zone the area between the vascular and a vascular and it can be some difficulty with zone one and it requires training the I'm not sure why zone one I don't think there's difficulty with someone I'm going to take that out but that must have been something I read somewhere so anyway I don't think there's any trouble with someone into it oh I know why I said that because sometimes it's hard to tell zone one from so to unless you have a 28 doctor lens wide angle imaging it permits longitudinal valuation it takes away some of that subjective diagnosis it gives you the opportunity of quantitative measures of plus disease and the concerns are in order to get wide angle you lose resolution so sometimes some of the images are not don't give you enough information to be able to distinguish stage three especially flattening vascularization from just normal retina and it's very difficult virtually impossible to evaluate zone three so what's happened is they've come up with a new classification called referral warranted ROP so if you're in rural United States and you have a neonatologist or neonatal nurse doing imaging the idea is that they would send images to a reading center and the reading center would look for these three characteristics any stage three ROP any ROP in zone one or plus disease and if any of those is present that baby has referral warranted ROP and should have an examination with and may need treatment so it doesn't it's not treatment it's just whether or not that baby needs to have an examination so there was a big study and we were a site for it called well it's we call it EROP but it has a long name for telemedicine for ROP and it provided strong support for remote evaluation of a referral warranted ROP and there was pretty good integrator agreement for zone one plus disease stage three ROP and it hasn't actually there's not actually that none of the study says this is prime time to do telemedicine for ROP I think probably because of legal reasons but I think using it in combination with examinations and having a system set up I think will be important especially moving forward in the future the number of ophthalmologists who are qualified to do exams and even treatment is becoming scarce throughout the world so it's a problem and we need to address it now the level of severity for treatment so you know again I said sort of prevention we're doing screening we're going to do now treatment and diagnosis of severity so based on the cryotherapy for retinopathy prematurity study in which the idea of the question was does cryotherapy reduce a bad outcome in babies who have severe ROP they look for a 50 50% risk of bad outcome and those infants happen to have the following characteristics on the left side zone one or two disease five contiguous or eight total clock hours of stage three so it was always stage three four quadrants of plus disease and as I said unfavorable outcome in 50% type 1 3p pre-threshold was tested in the early treatment for ROP study which use laser and and some cryo and found that these are the characteristics of type one zone one any stage of ROP with plus disease or zone one stage three ROP without plus disease zone two stage two or three with plus disease and the unfavorable outcomes were above 15% and the I think the reason they did the two or three is because sometimes it's difficult to distinguish two and three they're close in their appearance and then treatment with laser there's really strong evidence for that there is evidence for treatment of stage three plus disease in zone one so worse than type one we're talking stage three and plus disease in zone one and poster zone two based on the beat ROP study in which they use anti-vegeta compared to laser infants were randomized in that study there were a lot of concerns about the study and but but there are now clinical trials are ongoing to to be able to sort this out some of the positives about anti-vegeta are that it's just it's easier to do than laser laser really takes a lot of skill and so I think because of the fewer number of ophthalmologists that are available to be able to do the treatment it's it's it's just being adopted but we need to have more information the EGF is an important growth factor for developing infants and for neuro development potentially and so there are we need to have more information on dose there been no dosing studies but we're getting that the p-date study from that is testing de-escalating doses of evastant and severe OP worst site for that we hopefully will have information pretty soon that will be published regarding dose so again the pros for laser really strong evidence of efficacy and safety we understand the natural history in these baby cons maybe increase my opiate although a lot of the studies suggest that it's just if you have posterior disease that increases myopia and I don't think we actually know at this point because we don't have any infants that we've followed more than you know three or four years so the myopia progresses as the infant becomes a child pros for anti-vegeta it does increase vascularization in the avascular retina by inhibiting vegev R2 over activation and our lab was the one that found that and it does reduce proliferation in one major clinical trial and so on stage 3 rop in which it also promoted vascularization of the vascular retina so there's evidence in human that it does as well the cons are mainly that we just don't know enough yet we don't know the right dose we don't know the right agent treatment varies with each infant and yet we give the same dose like when you think about it people are saying well in India that it has this great effect and in India that infants are 36 weeks gestational age they're getting it they're much older they're almost twice as big as some of the premature babies that we are treat in the United States anti-vegeta gets into the system that's been shown it gets into the bloodstream it's diluted less in the growth restricted infants because the blood volume is less the blood volume is about six percent of the infant's weight and kilograms so yes we don't know if it's if it's actually active but serum that Jeff also goes down and it can stay down for two months so there's a lot of information we just don't know yet so the studies are being done and and that's important but for the individual infant we have to deal with each one individually and we take into information all the studies and series and everything done and what the infant has before we move forward for all we know maybe too much VEGF is also harmful you know that's that's a question we just don't know what normal is for premature baby anyway here just now we're going to go through slides pretty quickly so here are some just current this is one of the treatment you treat the avascular retina all the way around not just in the area of this stage three this is what it looks like we often do reticam images after treatment to make sure we don't have any skip lesions because they're very easy to develop when you're depressing the eye to put in laser treatment the eye gets really soft and then you get these valleys where it's hard to see the a vascular retina so you miss miss and you can get skip lesions the skip lesions need to be filled in a little if they're not filled in right away at a later time to reduce the vascular activity of the eye so stage four ROP progressive stage four ROP this is a really important it's very so it's very important to be able to assess when is the right time to go into these eyes so that so in the adult we have four to six millimeters to go in so we don't hit the land so we don't hit the retina in the full-term infant we have point eight seven millimeters so we don't want to hit the retina because that's inoperable that can lead to an operable situation we don't want to hit the lens because that's bad for the visual development of the infant so the decision on when and if to operate on progressive stage four ROP is important so we studied that too and and we found that there were really three things that were important the extent of the ridge elevation the presence of plus disease and vitreous condensation and those were the things that we taught that we would we found to be significantly associated with progression of disease and and what we didn't find to be important for going in and operating was vascular activity new neovascularization in those cases retreatment with either anti-vegetable laser was what was important so this just kind of shows you with a reticam you can tell with the reticam image you can see that the ridge is elevated because the vessels around the optic nerve are blurry so you're looking at two different focal planes in the lower right so again lens sparing the track to me our goals are to go in safely avoid the lens and then we basically have sorry I wish I had a good so we basically have various forces and and we decide which forces to address sort of based on the configuration of the retinal detachment but we we want to remove the circumferential force between the ridge and the enter part of the eye there's also one to the lens and and enter a poster and then there's a circumferential kind of trampoline effect that we we also release and once we do that then we get out and so here's an example but stage four op I don't know if this is going to work but if it does it's okay so so just we make our incisions about a half a millimeter poster to the limb this and the eye small so I have a millimeter is pretty big I like to use a biome because the eyes squash with the avi you know they get pushed down and so our goal now this is a 20 gauge I don't use 20 gauge anymore but um is to release the traction so here's the ridge and so I'm going back and forth to release the traction there and then also along in the posterior part there it's a little jerky and part of the reason for the jerkiness is the lid speculum so all these things kind of bounce you around in the eye and that's why when I talk with people so here's a really good example all this is all this is scar tissue incorporated with retina but we don't want to cut that because we'll get a hole in the retina so I'm just releasing the the tractional vitreous between that scar tissue and the retina and then I just put a bubble in the eye not to flatten the retina but just to make it easier to sew it up so and um so and this is how this baby looked about one to two months later so you give it time to settle back and it's yeah you know it doesn't look pretty but it's attached you know it doesn't look like a state 5 ROP and the baby has some chance of himing vision so um I think we went over all this sometimes we do a scleral buckle depending on where the detachment is and for exudative retinal detachment which does occur after laser or treatment um it if it doesn't have a fibrous component I may watch that or sometimes I'll treat with subtenous steroids okay let's see and and now most of the time when we do stage 5 ROP which I hope I never have to do very often I do a closed a typical detractomy where I remove the lens and then just cut the scar tissue and use helon to help push down the retina posteriorly so that I can identify where the areas are to cut and try to use two-handed technique whenever possible but we used to do something called the open sky detractomy where we would remove the cornea remove the lens and then the reason I'm showing this I almost never do this anymore unless the cornea is hazy but you can see this is retina and that fibro vascular tissue and you can see what it looks like when you cut it you know you see the scar tissue and this is actually what the retina looks like later and then we put the cornea back on okay I am I think we talked about all this and these are some of the conditions that can occur later with ROP so there's a whole list um they can in the teenage years with myopia and as the eye grows they can develop the children can develop later retinal detachment so it's their retinal detachment throughout life and um and so they have to have continued monitoring okay so now I'm going to get into some cases so I'm kind of going to change the format so let's start to act again we're going to talk about some cases here so this is four-year-old boy with reduced vision in the right eye and this is how his retinas look these are his um you can see he's hyperopic and he had a little bit of hemorrhage by fluorescent angiogram and this is his OCT so does anyone have any idea what it might be schesis right it's excellent schesis it turns out he has a mutation in RS1 so he has neovascularization and there can be several reasons why these kids develop neovascularization we're actually reviewing our cases now to see where they follow but it may be because of a vascular retina within the schesis area um it sometimes is related to or there are several reasons why you can get vitreous hemorrhage and we're looking at it so one of them is neovascularization but the vitreous hemorrhage can also be because the schesis is splitting of the retina and the inner retina can be very highly elevated and put tension on the retinal vessels so excellent schesis is one of the things so for your OCAPs that causes non- leaking um cystic uh quote edema in the macula it's it's usually in a male it's excellent um it and it's associated with these vitreous veils vitreous hemorrhage peripheral schesis in 50 percent it can also be associated with retinal detachment and it's passed on the maternal side 60 percent have this ERG finding so not a hundred percent so we use ERG to help us find an electronegative ERG which is basically I think of it that the B wave there's a this would be what would be normal B to A wave right the B to A wave is is low so it has a low B to A wave so you see like almost no people here but it's not a hundred percent and that's I think really helpful for me to remember because I'll get a kid in that I say oh this looks like schesis and doing ERG and it doesn't come out and it's okay it still can be ERG so the RS1 gene encodes retina schesis and retina schesis is thought to be one of these proteins that that's important for keeping the retinal layers together and it probably has other functions as well it there have been described different anatomic features of schesis and there is definitely a difference in how some of these respond and act the infants that develop retina schesis end up having poorer outcomes so that this child had laser within the schesis to the abascular retina partially clear vision improved so I think that there's probably a poxic component to the neovascularization in some of these patients as well okay so so the take on and then we do sometimes operate on schesis I I'm pretty conservative with retina schesis if there's a retinal detachment I try to do a buckle if I can I look for a peripheral because you can get outer retinal holes there are a lot of inner retinal holes but if you have an outer retinal hole or a dialysis these are children they can get dialysis just like anyone else then I'll do a buckle but sometimes we go in and do a vitrectomy as well the thing about the vitrectomy I think you need to and because the vitreous membranes are often firmer more firmly adherent to the retina than the retina layers are to each other you can't strip them so I often will push the retina back in order to remove membranes from the so a slightly different way of treating it case two is a five-year-old with poor vision in the left eye no family history or poor vision no history of trauma right i normal so this is what it looks like any ideas what this might be this a boy coats disease very good um so the thing about coats coats is 80 percent in male but it can be in female then right 20 percent when you see the exonates in the macula that's not a good sign but look out in the periphery for the these peripheral retinal vascular abnormalities when you do that do an ua do wide-angle fluorescein angiography I mean if you can do wide-angle fluorescein angiography in the clinic that's fine but usually kids it's harder so you'll see these areas of avascular retina you'll see these tortuous telegictatic vessels and the treatment the treatment is laser to the areas of the leaky vessels and also to the micro aneurysm type of dilatations with long acting uh very low energy laser so you put it on continuous and you paint the vessels don't paint the normal they're just the abnormal and then scatter treatment in the area of avascular retina and the treatment is all the you know all the avascular retina so it's changed a lot from what it used to be now with wide-angle fluorescein and um it over time the exudates will disappear and then these these children need to be followed yearly throughout their adulthood because it can reactivate later in life and then look at the fellow eyes about 70 percent will have non-vascular or avascular retina and the periphery but that doesn't mean that it's pathologic it we just don't know so we're monitoring it it's more to help us understand why you would have a unilateral condition in this why would it be unilateral there are there can be severe retinal detachment too and we sometimes treat that but again we do in a way not to cause holes in the retina so it's very different than how we treat adult retina cases um okay uh some of the things here that we want to talk about when you have by definite bilateral of exudation think of vascular, scapula, humeral, muscular dystrophy because that is an association with Coates disease and there are too many other clinical associations with it there have been staging of Coates disease back Gomez Morales this was pre angiography came up with this class of stages the shields kind of adapted it based on angiography so we often talk about these different levels of Coates disease hopefully what we want to do is be able to get telangiectasia only without exudates in the macula those kids do the best that's often the cause of poor vision okay so this is the that that child that I presented in the first so this is 13 months after laser and 21 months after laser vision is about 2060 now he did have some anti-vegetable treatment I treated with anti-vegetable mainly to see if I could prevent a corretal and the imascular membrane from forming but I don't think we really I don't think the evidence is that strong one way or the other that's that's to tell me I have five minutes before we go over the quiz okay so now here's a good example of Coates all right so this is a child that comes in with exudates had reduced vision I think right vision was 2070 in the left eye reduced vision you can see the the vascular abnormality here the exudates coming down here so partial retinal attachment this is the this is what his OCT looked like but look at the phobia the phobia looks great so the visual acuity is probably not from the exudates right it turned out he had ambliopia and so don't you know always consider the visual rehabilitation part of all these conditions this is how he looked at like after laser treatment so much improved so this is what we want to find with okay with Coates disease so three-month-old infant infant refer for persistent fetal vasculature in the left eye so what this is showing you this is a vascular retina all the vessels are pulled up into that fold so this is the fold of retina and this was the other eye so this other eye retinal vessels hemorrhages up into the into the vitreous cavity and when we look at the angiogram we actually see that there's neovascularization and periphery and as you see this is it because all the vessels are in that fold no other family history known no rashes no hair skin tooth anomalies and female family members do you know why i was that's important in the history so one of the causes of this can be incontinentia pigmenti and that that's in females because it's x-link dominant so it's lethal in males but it's not bad and do you know what it is fever so this is a full term infant that had this um a vascular retina so we treated with laser and i've been you guys know this baby i've been treating her i mean treat her fried i mean i've been seeing her every four to six months since she's now four years old said she was three months old so left eye i didn't couldn't do anything to treat that's the right eye i've treated with laser she had a growth spurt and she ended up developing a tractional detachment i've done lens bearing detractories and buckles on her so but she's still able to play t-ball you know so she still has some vision so they take you know these kids take any vision you have and do a lot with it so that's why we keep doing trying to make it better this was an lrp five dominant mutation mother also has that mutation but there's only pigmentation peripheral retina she's totally normal even on white ankle fluorescent angiography so that's one of the things about fever it can have extreme differences in expressivity and variability even between the eyes so um treatment is laser to the peripheral eye vascular retina some people treat with anti-vegeta i i think the evidence is not as strong with that but but these are full term infants i didn't do that with her because she only had that one eye i might have been more willing to do it if she had two eyes and treat one eye with it i was afraid of a crunch phenomenon um so the main causes that we know about are are the mutations in the wind signaling pathway so noren which also causes nory disease but you can get excellent fever first of four um lrp five t-span 12 and then this is not part of the wind signaling pathway there's znf 408 and then there've been new mutations in kiff 11 and beta ketene remember that lrp five can be associated with this condition osteoporosis osteopenia pseudokaliuma syndrome and we don't really have a good treatment for that but dexa scans and endocrinology this is recommended um it has been described with the george syndrome which is immunodeficiency and poor growth kogenal microcephaly um and it has a lot of variability so the wind signaling pathway here usually you have a wind that binds to frizzle four lrp five there's also another co-receptor lrp six t-span 12 is a tetraspanin so it kind of is somewhere in the membrane i believe and then this is the pathway that that goes into beta ketene and signaling noran the the ndp mutation noran can also bind frizzle four and lrp five so i think you have access to this whole thing don't you like i mean won't i i'll give you this so i think you can have it all if you want to look at that because i want to go over the um let me see i want to go over the the quiz with you i do want to just talk a little bit about non-accidental trauma because you do see this so it's related to shaking or blood trauma to your brain and you can get these schesis cavities and bleeding in all layers of including the just under the hyloid right so if you have a child like that and they have subhyloid bleeding that doesn't clear it can be helpful to do surgery to remove the blood so that they don't develop anisotropia they can actually get really myopic and one eye versus the other if there's a difference or just myopic in both eyes um and ambliopia and they're usually infants so we think about every one week for how long the blood has been there especially if it's really really at birth that they're near the time of the um right near the time of birth sometimes what you can do is just have them stay upright in like uh whatever those things are the kids hang out and like this yeah exactly and then that way the blood can settle so if you see that happening they'll be able to it'll clear over time and then they may not need surgery and and then maybe you know enough to be able to be sure they don't get ambliopia so uh sdoct can be helpful sometimes in interming the vitreous and the schesis and work with a pediatric team