During this live webinar, we will discuss cases of pediatric patients with systemic conditions. This webinar will delve into the low vision management of a case of Alstrom Syndrome, Wolfram Syndrome, and Hermansky-Pudlak Syndrome. Both the systemic and ocular findings will be discussed and recommendations for management will be provided.
Lecturer: Dr. Alexis Malkin, New England College of Optometry (NECO), USA
[Alexis] We’re going to spend some time talking about some pediatric low vision cases this morning, or afternoon or evening, depending on where you are tuning in from. I titled this “It’s Not Rare If It’s In Your Chair” because these are relatively rare diagnoses, but they do show up and it’s important to know what it is that your patient may be needing comanagement on, particularly with the systemic syndromes. I’ve kept the presentation relatively short in terms of slides so that we have some time to talk about the cases through the Q&A at the end.
Like I said, I’m going to go through a case discussion of three low vision cases with somewhat less common etiologies. We’ll talk about Hermansky-Pudlak syndrome, Wolfram syndrome, and Alstrom syndrome. And I’ll talk to you about how they presented in low vision, what the systemic associations are, and then we’ll go back to the low vision case and talk about how we managed them visually.
In terms of pediatric low vision and blindness, to set the stage and make sure we’re all talking about the same things, there’s about 14 million children worldwide who are blind. And although we don’t have really, really updated statistics on the types of conditions that can cause vision impairment or blindness, we do know that cerebral vision impairment and optic nerve anomalies, like optic nerve hypoplasia, are the more common causes, particularly in higher income countries. But recent work by Solebo and colleagues in 2017 showed that developing countries are actually shifting to more closely resemble higher income countries in terms of the causes of pediatric low vision and blindness. And this is primarily due to a lot better access to prenatal care and maternal health care, as well as better care of the premature babies. And so we are seeing this shift, so worldwide the causes are starting to line up more with each other rather than the divide between developing countries and higher income countries.
We also see retinopathy of prematurity and congenital cataract as common causes of vision impairment in kids. And we’re seeing more retinopathy of prematurity again. There had been a pause in that because we were able to titrate oxygen levels better in the neonates. But now technology is allowing medical providers to keep the really young babies alive and so we are seeing more ROP as we’re having those earlier and earlier preterm infants born who are able to survive. It’s a great medical advance but it is leading to more ROP again.
When we think about the general considerations in pediatric low vision, it’s not that different than an adult. We’re looking at what is that patient’s function, how are they doing, are they able to manage their daily activities? But we should also keep in mind what those pediatric daily activities might be. I really focus on ensuring that my history talks about educational goals and needs, where are they in school in terms of what year are they? Are they meeting expectations based on their age, how are their developmental milestones if they’re much younger? And are they in a standard classroom receiving services alongside students who don’t receive services or are they in a special school that is specifically focused on either the vision impairment, or if it’s a multisystem problem on their general health as well as their vision?
And we have also seen that pediatric patients can be more hesitant to integrate low vision devices. There are some social pressures, especially as kids get a little bit older, we see some device abandonment, usually around age eight is where that self-awareness can really kick in. And kids may be less likely to keep using their devices even if they were using them early. But we do focus on exposure to devices before age eight when possible in the hopes that we can prevent some of the abandonment that happens a little bit later.
And then for my pediatric patients, I also find that there can be significant care coordination that takes place when making these recommendations. We really need to work hard on making sure that we are connecting to school related services as well as, in many cases that we’ll talk about today, to those primary care doctors, to, perhaps, an endocrinologist and ensuring that both the vision and the systemic health are taken care of. As well as the rehabilitation professionals like the mobility instructors, the teachers of the visually impaired, the rehabilitation teachers.
Let’s just quickly talk about ROP. I’m not going to spend a lot of time here because that’s not the focus on the lecture, but just a reminder. Retinopathy of prematurity primarily affects premature infants who are under 1250 grams and born before 30 weeks of gestation. These twins met both of those criteria. ROP gets staged by its severity and the mildest forms don’t require treatment. In advanced cases, the babies can have tractional retinal detachments. Typically we see treatment with laser but the more recent literature suggests equal efficacy with anti-VEGF. And obviously anti-VEGF doesn’t cause retinal scarring, so we are seeing a push towards anti-VEGF injections rather than laser in the NICU babies. And that’s what these twins had.
In addition to the ROP, as I mentioned, neither one had a retinal detachment which is fantastic, they both were successful with the anti-VEGF. They also had albinism. Albinism, which I think everyone on here probably already knows, it’s an inherited condition with reduced melanin in the skin, hair, and eyes. It is characterized by foveal hypoplasia, as well as high refractive error, nystagmus, and strabismus. There is a really large range in acuities that you can see with people with albinism from mild loss through legal blindness. But typically about that 2200 to 2400 is about the worst you see in albinism.
That is a specific type of albinism that includes a platelet dysfunction. It’s characterized by easy bleeding and bruising and that’s often what leads to the diagnosis. Kids that get a lot of bloody noses or have a lot more bruising than one would expect. In some cases, the patients with Hermansky-Pudlak can also have lung fibrosis, colitis in about 16%, or abnormal storage of ceroid lipofuscin, a fatty substance that can lead to liver disease. Hermansky-Pudlak is actually the third most prevalent type of albinism, although it is still fairly rare. And we see it most frequently in patients of Puerto Rican descent. Particularly in the US, we will see Puerto Rican immigrants who are now living on the continental United States and so we do see this occasionally. In that Puerto Rican population in northwest Puerto Rico, about 1/1800 people in that region have Hermansky-Pudlak syndrome and 1/21 are carriers. Relatively high frequency of people in that specific population are carriers of the gene.
As I mentioned, Hermansky-Pudlak is often first identified because of frequent or easy bruising as well as bleeding gums or other excessive bleeding that is atypical for what you would expect in young children. And just like all other forms of albinism, the pigmentation can vary. Some people with Hermansky-Pudlak can have relatively normal appearing pigment. They don’t look necessarily as light skinned as one would expect of someone with albinism. The twins that I was seeing definitely looked like they have albinism but they do have some pigment.
Hermansky-Pudlak is autosomal recessive. As I mentioned, 1/21 are carriers and it’s a mutation in one of these genes that I listed. Our patients had Hermansky-Pudlak the HPS3 gene, but there are about 10 total genes that can cause Hermansky-Pudlak.
In terms of treatment and what you’re thinking about if these patients are presenting to you, as you would expect, because it is a bleeding disorder, you want to avoid aspirin. Transfusions may be required if there is significant bleeding that goes on for extended periods of time. And in acute bleeding episodes there’s some research that shows that using Desmopressin may be effective. Ultimately, if your patient ends up developing pulmonary fibrosis, they may ultimately need a lung transplant or other more aggressive treatment of the lung disease. Luckily in the twins I was seeing, they just monitor them for bleeding and they have not had any lung or other systemic issues. You can also treat with platelet transfusions but the research says they should be used sparingly because of the risk of rejection after multiple transfusions. Because it is a genetic cause of the platelet dysfunction, there is a risk of antibodies developing leading to the rejection.
I’m going to save all of the questions until the end because I think that that will be the most efficient to make sure we get through the cases but then we will have time for those questions.
We’ll go on here to the second case. This was a seven year old, referred for low vision evaluation by neuro-ophthalmology. And she was referred because she has significant optic atrophy in the setting of Wolfram syndrome. She was a complicated case because there were some language barriers in addition to the hearing loss. She came to the first visit accompanied by her sister and her mother. And her sister was assisting with the interpretation as the hospital where she is seen only has interpreters by phone. But her mother is deaf and a Spanish speaker and my Spanish is not fluent so we needed to use the interpreter over the phone, plus her sister helping with interpretation when her mom wasn’t able to hear the information. And we did put in a request for follow up visits to have an in-person interpreter to ensure that there were no additional barriers to providing the information to her mother. In addition to the Wolfram syndrome, she does have a systemic history of alopecia, hearing loss, which goes along with Wolfram, as well as sleep apnea. She’s not currently on any medications and it sounded like the diagnosis was relatively recent.
Let’s talk a little bit about Wolfram syndrome. It is a syndrome characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. Although I think most people probably remember the difference, just in case, diabetes insipidus is a type of polyuria or frequent urination with normal blood sugars. It’s not related to insulin or blood sugar. What’s happening is that the body isn’t creating the appropriate concentration of urine. It’s a kidney-mediated disease, typically caused by issues with vasopressin production. Diabetes mellitus we all know, I think, can also have polyuria, but it’s related to the blood glucose. And in Wolfram syndrome, they can get both of these. So they can have the kidney disease related to issues with vasopressin production as well as the pancreatic disease related to insulin concerns. Wolfram is an inherited condition. And it’s related to a mutation typically in the WFS-1 gene. And less commonly in the WFS2. It’s typically autosomal recessive.
Wolfram syndrome is relatively rare and because of that the presentation and onset of symptoms can be highly variable. But typically we see the development of diabetes mellitus as well as optic atrophy by the age of 16. And less than half also develop diabetes insipidus. But it’s something to be watching for especially when the symptoms could be similar to what’s in diabetes mellitus. The kidney function is monitored closely in patients with Wolfram. Interestly, to me, I was surprised that a seven year old had the diagnosis of sleep apnea, but as I learned more about Wolfram syndrome, I had seen that it was often associated with sleep apnea. Some patients with Wolfram syndrome also have urinary tract abnormalities separate from the hormone-mediated kidney disease. Close monitoring with the genitourinary specialists, renal specialists, nephrologists, you’ve got to watch all the different pieces and make sure that one symptom isn’t being blamed on one particular problem when it is common for both genitourinary tract issues to happen as well as kidney disease.
Often patients with Wolfram syndrome have ataxia and poor balance. And that is something that was happening in my patient that we’ll talk about more, but understanding what parts of her mobility issues are related to the Wolfram and what parts of her mobility issues are related to her vision. And finally, this part was very interesting as well as there’s a much higher incidence of depression and anxiety in patients with Wolfram syndrome. I think we could easily explain that as kids getting diagnosed with a pretty significant systemic syndrome, but they actually think that is related to changes in the nervous system which cause the optic atrophy as well as the ataxia and the hearing loss, that those changes also lead to the depression and anxiety rather than just quality of life types of concerns. Though both are probably factors in these cases.
For Wolfram syndrome, you need to treat the coexisting conditions: insulin for diabetes, vasopressin, sorry there’s a typo there, but vasopressin for diabetes insipidus. And then really making sure you’ve got the right people co-managing. You hope that whoever made the diagnosis checks these different boxes, but I find that the low vision assessment can be a time to really look at the full systemic picture and ask who else are they seeing, who is involved in the care? And if you don’t have a good electronic medical records system where you can share all of the notes, make sure that the patient and their family has access to the notes to share among the different groups. They recommend referral for neurology consult, as well as hearing consult, and a sleep assessment if they haven’t already received that diagnosis of sleep apnea, because it is very common in Wolfram.
Let’s go back to our case. This seven year old came in and we wanted to get into her functional history. And she’s having a hard time with a lot of different aspects of her vision. She has a hard time seeing small print and she sits at the front of the classroom to see the board more easily. She has a hard time seeing to take notes, hard for her to see her handwriting. And for her daily living activities, her mom felt like she did less than similar kids in age. She relies on her family for things like cleaning up her room and helping with basic chores around the house, like setting the table. And her mom wasn’t sure if the vision was why she wasn’t doing it or if there was something more going on. In terms of her mobility, she has had multiple falls and she frequently bumps into things. That’s why that question is, is there some ataxia, or some sort of neurological balance concern going on or is this all related to her vision? And I suspect that it’s probably a degree of both. She does have an individualized education program in place for school. And she reports that she doesn’t like school.
In terms of her ocular findings, she really shows significant fluctuations visit to visit. I’ve seen her a number of times now after that first visit where we were just getting to know her. And she ranges from as bad as three feet/300 and three feet/400 on a Feinbloom chart isolated numbers. To as good as about 20/100 on a Snellen chart. And it’s day to day, so it’s not that she’s progressed from 20/100 to worse vision, it just depends on the day and how she’s accessing her vision. In addition, her contrast sensitivity fluctuates quite a bit visit to visit. She ranges anywhere from .72 log units as her worst measurement, so pretty severe for her age and severe even for an older adult. And her best measurement is 1.20 log units. That’s moderate loss if we were talking about an adult but still relatively severe loss for someone her age.
We’ve refracted her numerous times and she really has no improvement with lenses. Although she does often tell us that plus a quarter makes things significantly clearer, I think that there is a psychological factor hoping that glasses will make it easier for her because she is really struggling with her vision impairment. Her confrontation visual fields have shown constriction 360 degrees in each eye. And so far we haven’t been able to get a reliable Goldmann field with her.
In terms of our reading assessment, she is not yet a fluent reader and she’s below grade level for all of her reading tasks. She did read spotting letters on our lighthouse near spotting card, some spotting letters and some shapes. And she read to about 10M, so really, really big print was all that she was willing to do in our exam. That gives her a Feq or estimated starting power for near of 40 diopters. This was pretty atypical of what I would expect in a young child. Typically they hold things pretty close, they rely on their accommodation and they’re able to do a bit better at near. She wouldn’t hold things any closer than 25 centimeters and wouldn’t read smaller than the 10M print. But I think that generally she’s struggling so much understanding her vision that we ran into a little bit of an issue there with pushing her to get to smaller print because it’s hard for her to access her vision and utilize it effectively.
We looked at magnification for reading based on that 40 diopter Feq, we started a bit lower power, we started even with some dome magnifiers. But she really didn’t have a very good response to magnification for reading. For whatever reason she felt like it was making things worse. She did have improved spot reading when we looked at a telescope for distance. And we started with a 2.5X. I typically start with that lower powered telescope, like a 2.5, just get a sense of how a pediatric patient responds. Some kids do great and they immediately take to the telescope, they can focus, they can localize. And then we can go up in power to something that we think would be a bit more appropriate. In her case, she had immediate improvement and she got to 20/70 vision, but when we went to higher power she stopped gaining acuity. It was unclear whether she was having trouble with the small field of view because of her constricted fields, or a contrast issue, but she didn’t get better at higher powers.
We tried some digital magnification, using a portable CCTV again, just to see if we could get better visual engagement and sometimes she seemed engaged and seemed to like using it and sometimes she didn’t. It was hard to get a good read on what was making her more comfortable visually.
In terms of her plan of care, she has a complex condition and I suspect that the neurological factors are really playing a big role in why her responses are so variable. But I encouraged exploring the devices again in her classroom and at home because of what we were seeing in the exam room. That it was sometimes working and sometimes not. But the exam room is not necessarily the best place to assess low vision devices in pediatric patients. I was concerned with multiple disabilities, including the hearing loss, that she had not had a formal learning media assessment yet to determine her best learning modality. She reports a lot of difficulty at school and just doesn’t like school in general. We talked to her teacher of the visually impaired and they did have plans to do a learning media assessment for her to figure out if she should be using other tools to help her with her learning.
We always encourage the ongoing work with her teacher of the visually impaired and she was doing that. And based on her reduced acuity at near in the exam room and her unwillingness to hold things closer and use her accommodating, we recommended that they start by enlarging the font on all of her materials to begin with. Over time she may be able to access materials in smaller print and utilize devices. And we don’t want her to rely on someone enlarging things long term because for life that’s not going to be a really sustainable solution. But for her immediate needs where she isn’t able to access her school materials, we did recommend two to three times her threshold to allow to begin to learn to read more effectively if that’s going to be a possible solution for her. But at least to make sure the print is big enough when she’s trying to learn to read.
We recommended bold pens based on the reduced contrast sensitivity, as well as reducing the crowding of the materials that she’s presented with. Many times elementary school worksheets have lots of information on them, lots of subdivided groups, and so we recommended that they reduce crowding and present her with less complex materials at a time so that she can better visually engage with what she’s receiving.
In terms of Alstrom syndrome, symptoms generally present in infancy but it can be variable. Just as we talked about with the other two syndromes, it has pretty significant systemic conditions. Alstrom is usually associated with both vision and hearing loss and it is autosomal recessive. It is associated with mutations in the ALMS1 gene, which is where his mutation was.
The vision problems in Alstrom syndrome typically start with a cone-rod dystrophy that eventually leads to legal blindness. And most children with Alstrom syndrome have nystagmus. When he presented to me I thought that he sounded a lot more like he had a cone dystrophy just based on the profound sensitivity to bright lights as compared to a retinitis pigmentosa where you would typically early on expect decent tolerance of bright light and worse function in the dark. That matched what we ended up getting with the diagnosis. I wasn’t expecting Alstrom syndrome to come back as the diagnosis, I was expecting some type of cone dystrophy.
Systemically he is now managed by an entire team at one of our large hospitals here because it is associated with progressive hearing loss, with cardiomyopathy, with childhood obesity, with insulin resistance and type 2 diabetes, hyperlipidemia, fatty liver, short stature, acanthosis nigricans on the skin, as well as hypogonadism. In his case he does not have short stature, he is extremely tall. But he had been struggling with childhood obesity and the mom was working with the pediatrician to try to figure out. He was eating just like his siblings and was just gaining a lot more weight and they were really having trouble understanding what was going on there. She was really grateful for this diagnosis because it helped her understand that it wasn’t anything she was doing and it wasn’t anything he was doing, he was predisposed to childhood obesity and he’s now being watched very carefully to ensure that he doesn’t need treatment for the cardiomyopathy and that he doesn’t develop type 2 diabetes. So far all has been clear from cardiology and endocrinology and they’re just watching closely.
With Alstrom syndrome, as you would expect, there’s no specific treatment for this syndrome itself. You treat each condition as it develops and it’s that careful management with a team of specialists, and pediatric geneticists potentially, to look at each systemic condition and treat what needs to be treated. The medications can include insulin, or ACE inhibitors, or hormone therapy if short stature is a major problem. And referrals for vision services like low vision as well as audiology are recommended to make sure those services are integrated early.
In conclusion, these are three unique pediatric cases that are caused by rare systemic syndromes. But each pediatric case still has the same common themes, looking at the educational goals, assessing the vision, and figuring out what low vision aids may be helpful. We have a unique role where in addition to assessing the vision, we can be the people who can look at the comprehensive care that the patient is receiving and just make sure that their pediatrician is aware of that systemic condition or that perhaps that their ophthalmologist is aware of who else they’re seeing. And just make sure that the care coordination is happening. And that the school system understand that there is more than just vision going on because that makes it a little bit more complicated when you’re working with these kids in the classroom.
Our plan of care just should take into account the complex needs of these patients. Sometimes they’re overwhelmed by all of the medical appointments they’re going to and that may make the patient even more hesitant to integrate the low vision devices while they’re undergoing all these other major medical treatments. Allow your patients to communicate to you and tell you what’s going on and what tools seem helpful, and what doesn’t seem helpful. And even at age three, four, or five, or even younger, kids can let you know what’s working and what’s not working. Listen to the kids, listen to the parents, and make sure that you’re looking at that complete picture as you make your updated recommendations.
There’s a question here that says is it possible for a four or five year old child that they’re having problems holding the dome magnifier or the telescope? For the most part I’ve actually seen that even two and three year olds can handle the dome magnifier pretty well. Some kids not so much, but usually I like to see what happens when I hand them the device to figure out if they’re able to handle it well. Some kids do great and some don’t. Some put the telescope right up to their eye without any additional education and some kind of put it at their nose or the middle of their forehead or they have a lot of trouble using it. I like to just gauge with a particular patient to watch and see what they do. And sometimes it’s they’re too young and we need to wait a bit and we will look at it later. Some do great, some don’t, it’s really variable, it’s kind of true with our older adults as well. Some do great handling devices and some don’t.
Some of these are just comments. This is a question about do you recommend sibling examination in the case of a child with low vision? I do. I recommend a comprehensive exam for kids regardless. I would refer to the geneticist to figure out if that sibling should also have genetic testing. My guess is that’s already been discussed with the family but I do usually ask that question. I have a whole family of kids with dominant optic atrophy who I follow and three of the four siblings have it. And we’ve worked with the geneticist to figure out whether it makes sense to test that fourth sibling and so far they’ve said no because there’s no treatment and he doesn’t have any symptoms. But we do a comprehensive exam with them anyway to make sure that they’re doing well. And I think it is important to talk to the parents about whether the siblings may have issues and in a case of something like Alstrom syndrome, they may recommend really early examination of any siblings, they may even do genetic testing before pregnancy to figure out is there additional risk, was it a new mutation? But in their case they weren’t planning on having more children and they said they’re pretty certain that both parents were carriers and that it was the autosomal recessive mutation. Definitely worth talking about if there are siblings in case they are also carriers of the condition.
In Wolfram syndrome, carriers can have mild symptoms so we think that’s what’s going on with the mom who is deaf of the patient I see. Mom’s never had genetic testing but we assume she’s a carrier because she does have hearing loss.
Case three did go through initial electrophysiologic testing and it was inconsistent. It didn’t really match the presentation of retinitis pigmentosa so I had been surprised that’s what we got diagnosed with. It looked more like a cone dystrophy to me when I read the ERG. They have not repeated his ERG at this point because they know that it is a cone-rod dystrophy because that is what happens in Alstrom syndrome and it matches all his clinical findings. They haven’t retested him in terms of electrophysiology mostly because they’re going to perhaps do it when he’s older so he won’t need an exam under anesthesia at that point. But right now it would just be academic, they don’t really need that additional information.
There is a question about visual acuity measurements, were they all single optotype? Actually they were not. Some of them when I did the Feinbloom, that’s mostly single optotype. But the others were typically reading on a ETDRS chart, actually. Multiple optotypes with some crowding which probably showed worse acuity than they might be able to achieve if we did single optotype without crowding. But when the kids are able to do it, I don’t necessarily isolate the lines unless I need to to add information to what the teachers are doing in school.
There is a question about Leber’s congenital amaurosis, there’s nystagmus and glare and how would you treat it? Similar to the case with Alstrom syndrome, I actually thought he was going to come back as having Leber’s based on the high refractive error, the nystagmus, and the glare sensitivity. Or just a general cone dystrophy. You would actually treat the symptoms. Perhaps you would use prism to help get into a null point with the nystagmus, you would use tinted lenses, you would correct the refractive error, and then whatever low vision devices helped improve the visual function as well. Pretty similar management in that case.
There’s a question about the VA after refraction for case three. I gave you best corrected visual acuity in case three. That 2320 that he was achieving was his best corrected visual acuity.
There is a question about whether I’m using the 2.5X monocular telescope in my assessment and whether I would use binocular and if there’s any difference? I typically use monocular only because it’s small and easy so the child can hold it pretty well. I like to see which eye is dominant, which hand, which eye do they go to automatically. But I don’t think there’s anything wrong with doing it with a binocular telescope as well, because they are functioning binocularly so that may be a quick, easy way to assess it as well. I’m just trying to gauge their response to distance magnification. I think that would be appropriate as well, unless you have dramatically different acuities between the eyes and then they’re really only using one with it anyway.
I know there are some concerns, there’s a comment about the cost of low vision devices. That is a very true statement. The reality with a lot of the tools is that they are expensive. It’s always why we look at some of the domes and the low cost telescopes, those are pretty easy to integrate and they’re not super expensive the way that a video magnifying might be. And so we do try to go to the simpler, lower cost devices to start with and then if needed we can even get a low cost tablet in some situations if we have to. But presenting materials in high contrast, printing out the pages in black and white, can help circumvent the need for some of those digital devices as well.
It’s a question on visual field testing in pediatric patients. You can get them in really, really young patients. There’s some research being done on using modified techniques in infants. My colleague is able to get Goldmann visual fields even in two year old patients. Where I have access to a Goldmann, it’s a little bit harder, we don’t typically do it until they’re maybe five or six. But a really mature three or four year old could probably do it. And maybe a less mature six or seven year old might not be able to. You want to gauge your patient to see if they’re able to.
All right, I think that is all the time that I have for questions. But thank you all for being here today. And we’ll see you again at another webinar soon.