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Heidelberg Engineering: Enhancing the Patient Journey

Clinical

1rem

A new amblyopia screening system that can be used on Android devices has performed better than some of the ‘gold standard’ stereotests in recent Hungarian studies.

Amblyopia screening with the dynamic random dot stereotest

A pair of studies, conducted in Taiwan and China, indicate that red light therapy could serve as an effective and safe alternative to atropine

Insights into atropine usage

Salvation of ocular tissues and visual acuity are dependent on early diagnosis, investigators emphasised

Patient outcomes in retinoblastoma impacted by parents' interventional delays

An ophthalmologic examination revealed bilateral anterior uveitis, though the patient had no ocular complaints at presentation

German case study illustrates systemic presentation of tubulointerstitial nephritis and uveitis

In a press release, the National Institute for Health and Care Excellence announced the first-ever approval for a mitochondrial disease treatment

NICE announces UK approval of idebenone for treatment of Leber hereditary optic neuropathy 

Enhanced screenings and a unified registry could save vision and lives

Managing and monitoring the global burden of retinoblastoma

At the Retina World Congress, we spoke with Siegfried Priglinger, MD, about ensuring the best outcomes for preschool-aged patients

At the Retina World Congress (RWC) in Fort Lauderdale, Florida, the Eye Care Network spoke with Siegfried Priglinger, MD. Prof Priglinger is director and chairman of the University Eye Hospital of the Ludwig-Maximilians-Universität, in Munich, Germany. The research he presented at the RWC focused on paediatric patients with inherited retinal diseases (IRDs), with an emphasis on studies into the RPE65 gene.

Prof Priglinger said that early intervention is key for ensuring the best outcomes for preschool-aged patients. One common IRD among this patient group is a defect of the RPE65 gene, which is responsible for activating photoreceptors in the retina. According to Prof Priglinger, it's up to general ophthalmologists to act fast when they suspect a patient may have a retinal disorder that requires specialist intervention.

"[General ophthalmologists] should always think of an IRD, and send patients to a specialist, to make sure these kids are recognised very soon," he urged. He went on to say that developing visual acuity is vital, and feasible for many young patients, who could experience protection or restoration of vision early on in their academic careers—a key indicator of long-term positive outcomes. "They can read and go to school, and just have a normal life," Prof Priglinger said.

He also noted that the world of gene therapy is expanding at an extraordinary rate, which could lead to an exponential increase in the number of therapies available. "What I would love is to have a treatment for every gene defect. It took more than 20 years for RPE65," he said. "Hopefully it's not going to take 25 years for each gene defect, but I'm pretty sure that researchers are going to solve this problem."

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Early intervention is crucial for long-term outcomes in paediatric gene therapy

Quan Dong Nguyen, MD, MSc, of the Byers Eye Institute at Stanford University School of Medicine, discusses his presentation on Stargardt disease at the American Academy of Ophthalmology meeting

At this year's American Academy of Ophthalmology (AAO) meeting, Quan Dong Nguyen, MD, MSc, of the Byers Eye Institute at Stanford University School of Medicine, presented as part of the late-breaking developments broadcast. Ahead of his presentation, "Tinlarebant (LBS-008) for Adolescents with Stargardt Disease," he sat down with David Hutton of 

 to discuss the research findings and their implications.

Editor's note: This transcript has been lightly edited for clarity.

 The American Academy of Ophthalmology is hosting its annual meeting in Chicago. At the meeting, Dr Quan Dong Nguyen is presenting data on Stargardt. Thanks for joining me today. Can you tell us the key points of this data?

 Thank you, David, for having me involved with your programme. It is certainly my great, great pleasure to share with you the work that our colleagues and I have been doing, looking at a compound called Tinlarebent, which we have been studying for adolescents with Stargardt disease. Certainly. as an answer, one can say that even at this time in the year 2024 we currently do not have any treatment for our patient with Stargardt. And throughout the year, we have very much witnessed the tragedy and the devastation when many of our patients, some of them are really young, are losing their vision to Stargardt disease. Patients affected with Stargardt disease, or STGD1, harbor a genetic mutation in a key protein within the retina, which then interfere with the normal vitamin A processing in the visual cycle, and which result in significantly increased accumulation of cytotoxic byproducts of Vitamin A, so-called bisretinoids, and with subsequent progressive retinal cell death.
Because these retinoids are derived from circulating vitamin A entering the eye, reduction of vitamin A delivery to the eye is therefore expected to reduce the formation and accumulation of bisretinoid, leading to reduced pathology and preservation of vision in patient with Stargardt Tinlarebent, the medicinal product being investigated here is a novel once a day oral tablet, completely non invasive, oral tablet designed to bind to serum retinal binding protein 4, or RBP4, as a means to specifically reduce vitamin A delivery to the eye in order to slow or hurt the accumulation of this bisretinoid that I have mentioned. It is our hope and believe that early intervention directed at retinopathology, which is not mediated by inflammation, would be the best approach to potentially slow disease progression in Stargardt as well in geographic atrophy. And again, David, here, I want to emphasize that we believe that early intervention is best here, because we don't want damage to have occurred and then at that time, we would not be able to replace the dead tissue. So we want to make sure that things are treated and managed at the very early stage.


We know that vitamin A is transported to the eye in a protein complex with RBP4 and transthyretin, or TTR. Unlike other tissue, the eye has a unique requirement for uptake of retinal-bound RBP4 due to abundant oppression of the RBP4 receptor, and this aspect from there. In Stargardt patients, this dysfunction of the APCR protein, which then results in the accumulation...and deposition of these complexes into the retinal pigment epithelium, then result in accumulation of cytotoxic retinoids I have mentioned, and then lead to retinal cell death. From this aspect, how does Tinlarebent work? Tinlarebent, as I mentioned, is a small molecule RBP4 antagonist that can compete with retinoid retinol for the binding of RBP4, and does not allow the binding of TTR to the eye. The Tinlarebent RPB4 complex are then liberated into the circulation and then eliminated to the kidney, due to its small size, and result in a reduced retinol delivery to the eye.


So in our Phase 2 study, we enrolled thirteen subjects that have no definite decrease in auto fluorescence and have questionable decrease in autofluorescence. These subjects were treated with a dose of Tinlarebent, 5mg/day, for the treatment duration of 2 years, and I'm sharing with you the result now, the 2-year outcome of that. The primary measure certainly would be the safety and the tolerability and the optimal dose. But we also look at other measures, just at DDAF, QDAF, visual acuity, OCT and microperimetry as well. And the key inclusion criteria here I alluded to, we aim for young subjects, patients. The criteria of age was 12 to 18 years old, diagnosed with Stargardt with at least one mutation identified in the ABCA4 gene. Definitely, we like to do that to make sure that we have the right patient and the right target. The 5 milligram daily dose: where's that coming from? That is being used because the 5mg daily dose have been known to effective, to be quite effective, in reducing the RBP4 level by a mean of approximately 80% relative to baseline. 

We also learned that RBP4 level returned to about 87% of the baseline value at the end of the study, like that. So we know that we can reduce the level we need, and then when we start using that, it's back to the normal level of that aspect. So in this study, over the 24 months, we have seen the change in QDAF and DDAF lesion size. We see that the transition from QDAF to DDAF lesions and growth of incident lesions was examined. In five of the twelve subjects, there was no incidence of lesion growth. In seven of the twelve subjects, we see no expansion of the autofluorescin...there. What about visual acuity? Visual acuity was stabilised during the study with a mean loss of five letters in the cohort over 24 months. Many of our subjects who entered the programme have shown significant bilateral vision loss prior to enrollment. For example, in a subgroup of six subjects, they have shown a mean of a ten-letter loss per year prior to enrollment. Following 24 month treatment in the programme, the mean visual acuity loss in this group was just three letters a year. So they went from ten letters per year loss, prior to enrollment, to, on the mean, just three letters per year. So quite a improvement in terms of the vision loss. And so, in addition, we also obviously want to make sure that this drug is well-tolerated. So we looked over the 24 month result, and we noticed some adverse events occur. 

For example, there were sentopsia and chromatopsia, but that the degree was very mild. The subject described to us that they experienced some of the symptoms, but they very quickly, easily adapted to it. So that goes along also with delayed adaptation and night vision impairment, they are all considered mild. And the thing that quite encouraged us was that, among the thirteen subjects who will enroll in the programme, none of them dropped out due to any type of adverse event. So yes, they recognise that there's some mild level of...tension adverse events...but that will very quickly resolve and everyone stayed in the programme. And we learned that Tinlarebent continues to be safe and well tolerated. And that is, it can produce a mean 80% reduction of RBP4 from that aspect. So we're very pleased with that. So in summary, David, we are very encouraged because, as we say at the moment, there is no treatment for Stargardt disease, neither for the adolescent or for adult. There was absolutely no treatment across the globe. There are several trials in the past looking for gene therapy for Stargardt disease, but all of them have failed. So at the moment, [in] 2024, we have no treatment. We were encouraged to, when we see a Stargardt a result in here, when we saw that, in this case, 5mg daily of Tinlarebent produced a mean 80% reduction of the plasma of RBP4 retinol, which was very reversible during the drug cessation. So it does what it does during the part we need. But then when we stop the drug, it's back to normal, so no long term or permanent damage. That visual acuity was stabilised in subjects in our study, and definitely did not show the type of visual loss before that. When we look at the lesions and the various type of measurement, grading it, we also note that the growth had halted from month 16 to month 24. So clearly, there's a benefit of the subject being treated, because the growth that we've seen before has slowed down and basically stopped from month 16 to month 24, and no systemic, drug-related adverse events have been led to discontinuation of patients. So we're quite excited about this. And certainly, we have done this study with significant help from our colleague from Australia and from Taiwan, two of the major countries that have contributed subjects and patient to this programme.


 What's the next step for this research?


That's the certainly another point that I'm quite excited to share. So since we finished the Phase 2 study, which I just shared with some results, we have started and already completed the enrollment for the Phase 3 study of Tinlarebent in adolescents with Stargardt disease. It is called the DRAGON study, and is an international study involving different continents and different countries. And we have finished enrollment for it already. We have passed the 1-year mark. And so we are waiting to evaluate the result at the primary endpoint, at the 2-year mark there. 

Hopefully, if that turned out to be what we have seen in this Phase 2 study, we are hopeful that Tinlarebent will have the potential to become the first treatment for patients, in particular for adolescents with Stargardt, because currently there's no treatment options. And suddenly those adolescents are the ones that we really hope that we can save the retina before getting too damaged. And then, in addition, David, to the programme in Stargardt, we have already launched a multicenter international study programme to look at the role of Tinlarebent in patients with geographic atrophy, another disease process that can lead to accumulation of the unwanted product in there. And we're hoping that would also show positive [results]. 

So the Phase 3 study of Tinlarebent in geographic atrophy, which is called PHOENIX, is currently occurring throughout the globe. The United States certainly one of the major countries, but we also have colleagues from Europe as well from other parts of the world, participating in that programme. We're looking forward to perhaps another potential treatment for patients with geographic atrophy, along with the Stargardt disease that we just mentioned.

A novel oral therapeutic showed promising results in a Phase 2 study involving 13 subjects

AAO 2024: Late-breaking developments in a novel treatment for adolescents with Stargardt disease

Noel Brennan, MScOptom, PhD, a clinical research fellow at Johnson and Johnson

At this year's ARVO meeting in Seattle, Washington, the Eye Care Network spoke with Noel Brennan, MScOptom, PhD. The clinical research fellow at Johnson and Johnson shared highlights from his presentation on myopia control and predictive modeling.

Note: The below transcript has been lightly edited for clarity.

Hi, I'm Noel Brennan. I'm a clinical research fellow at Johnson and Johnson. I'm here at ARVO 2024 in Seattle. I have a presentation here called 3-year myopia control efficacy can be predicted from 1 year data. Now, the background to this is that the gold standard for myopia control studies has kind of been a 3-year study. But there's a few problems with this, because keeping kids in a control group for 3 years is, perhaps, not ethically acceptable any longer. And in addition, we've noticed that some of the longer-term studies, the control groups seem to be becoming perhaps contaminated, as parents are aware that the kids are progressing too fast and maybe withdraw them from the study, or perhaps even seek treatment outside of the study protocol. So we wanted to see if we can predict these longer term efficacy numbers from short-term data. 

And our initial attempt to do this kind of failed, because we couldn't find enough studies that had 3-year control and treated groups. But, what we're able to do initially, then, was just look at progression. So we looked at 1-year axial elongation, and axial elongation is really the, the benchmark that we use for looking at progression. And we found a lot of studies for that had 3-year data, and the correlation was really quite good. And we could deduce from that, that you are getting double the efficacy at 3 years that you are getting at 1 year. So what the presentation here has done is built on that. 

We found a few additional studies that were published, and we went back and reviewed some of the earlier work that we had. And in the end, we found 15 studies where we could correlate 1-year efficacy with 3-year efficacy. And rather incredibly, the correlation was, the R-squared value, was 0.97, which is quite remarkable, even though the quality of the studies was not necessarily that great. So this is further support for that concept that 3-year efficacy is going to be double 1-year efficacy. And you might say why isn't a triple? And that's because we get this initial treatment effect in the first year that is that is quite large and strong, and it subsides over the subsequent years. 

And how do we make sense of this? You know, what, what what news can we report with all this information? Well, first of all, you know that from a regulatory standpoint, perhaps we don't need to do 3-year studies, and we need to review what we perhaps should do. The second point for clinicians, though, is if you have robust 1-year clinical data from a trial, you can use that to predict how well that particular intervention will perform in the longer term. And certainly now, from our perspective, this is what we base our understanding of efficacy on, it's the 1-year axial reduction that we see. And if you have a list of these, you'll get the rank order. And we think that's the way really that we should be moving forward for the future. So the next steps for this research really are that we're trying to put together a complete model, a comprehensive model, of efficacy, so that we can predict what's going to happen beyond 3 years, so to 6 years and 12 years, and we're well on the way there. So for ophthalmologists, you know, the key thing here is what does the 1-year data look like? So you need a robust 1-year trial, and if you look at the data and put them in rank order, that rank order is going to maintain over the longer term, so you can work out which treatments are the most efficacious. But the 1-year data really should be a multi-site, randomised, controlled trial with a large sample size, because we do see some data where the trials are not so strong in their design, and we get can get some strange numbers from that. So we do need quality, 1-year trials.

At this year's ARVO meeting, the Eye Care Network got a glimpse at the future of paediatric myopia control research

ARVO 2024: Predicting the efficacy of myopia control methods using 1-year data

Dr Srijana Adhikari speaks about her research ahead of the ARVO meeting

ARVO 2024: Using objective measures to gauge activity levels of visually-impaired children

This year's ARVO meeting is uniting vision experts from around the world in Seattle, Washington, for 5 days of fascinating programming. Ahead of her presentation, we spoke to Dr Srijana Adhikari, Head of Paediatric Ophthalmology and Strabismus at Tinganga Institute of Ophthalmology in Kathmandu, Nepal. Watch the video, or read the transcript below, to learn more about her research and its implications in future studies.

Editor's note: The below transcript has been lightly edited for clarity.

 Hi! My name is Hattie Hayes, and I'm the editor of Ophthalmology Times Europe. This year's ARVO meeting is in Seattle, and we here at the Eye Care Network are speaking to attendees about what they are presenting at the meeting and the data they're most looking forward to sharing. Joining me today I have Dr Srijana Adhikari. We're going to talk about her presentation, which is titled "Differences in objective physical activity between children with visual impairment and normal sight." Thank you so much for joining me today. I really appreciate it.

 Thank you. Thank you so much for inviting me.

Go ahead and just give me a brief overview of your presentation and what you're going to be discussing at this meeting.

 This presentation of mine is a part of my PhD project, which I'm doing on blind and visually impaired children. So in this whole project, we are looking at the participation, activities, sleep patterns and quality of life of children, visually impaired children. At the same time, we are comparing these outcomes with the normally-sighted children. And so in this particular presentation, I'm presenting on the activity part...What we did was, we recruited children. In Nepal, there is an integrated system of education. Blind children also study in the same schools as normal sighted children. So we took children, the blind and visually impaired children, and for and from the same grade and from the same class, we chose their friends, the normally-sighted friends, for the control group. And in those children, we studied activity: types of activity, different parameters, levels of activity, by using objective measures, like actimeters.

 Among these data you've collected, is there anything that surprised you, or anything you think that your colleagues might find surprising?

 Yes, yes. What we found is that...in studies on measuring the activity in children, most of these studies are from the patient-reported outcomes. Those are the, the subjective studies. But my study is one of the very few studies which was done by using the actimeters. And what we found is that we divided the activities into different levels, like sedentary activity, mild and light physical activity, moderate and vigorous physical activity. And at the same time, we compared them during the different times of the day, which is also very unique of our study. Before school, what are what are their activities? During school, after school and during the weekend time? So what is the difference between visually-impaired and normal-sighted children? Well, what we found was that before the school time, before they start the school day, in the morning, the visually-impaired children were slightly more active than the normal-sighted children. And during school time, the normal-sighted children were more active, more physically active, than the visually-impaired children. But after school and during weekend time, both were the same...both were involved in, most of the time, sedentary and then low-to-moderate type of activity.

So, what we found was overall, in all children, the sedentary activity was more. It shows that the children are not very active, not as recommended as by WHO criteria. That was one thing we found. And we found that most of the visually-impaired children, during the morning hours, were active. So why was this? Well, in Nepal, most of the visually-impaired children stay in hostel, and then they are in a boarding school. [In comparison] normally-sighted children live with their parents and they come [to school] from home. So the children who stay in the hostel, they do their own morning activities. They get dressed up, they may prepare breakfast, and all these things by themselves. They are trained like that, and they have to do all those things [independently]. But at the same time, the children who stay with their parents, most of the things are done by the parents...That may be the difference. That was one thing that we really found very interesting. And because children who get involved in all these activities, light activities, are more active.

But, however, during school time, the normally-sighted children were more physically active than the visually-impaired children, which, we think, is [because] there are so many barriers...The playgrounds of the schools were very good, they have assigned physical activity classes for all the children, but still, the children with visually impairment have less opportunities. And maybe there are some barriers, like, they don't have games that are suitable for them, like dancing, gymnastics, swimming. Those those things needs to be given, the opportunity should be given, to [play] those types of games, for visually-impaired children. They cannot freely play football, basketball, or something like that. So that was a very interesting thing we found.

We thought that maybe the next step we can do with this research is [ask], What is the actual barrier? Whether they are provided or not provided with the sports or the activities that they should be taking part in, or they don't have any trained teachers, or they have lack of motivations, or maybe some pressures from the parents or from themselves that they might get injured or something like that, that is the yet to see. But these are very interesting things that we found.

 That's really interesting. Now, I know that, you know, ophthalmology is a field that's rapidly changing. And I think that you feel that more acutely in the paediatric sphere. What do you think will be the biggest change in paediatric ophthalmology in the next 10 years or so?

 I think that myopia is one of the very, very important things that is very much going on. We see so many people [being diagnosed with myopia], especially after the COVID period. Many children in our daily practice, and data also shows the same thing. So I think there will be research still going on, and more will come, for myopia progression, that will be a big change, that what I think. Another thing is...visual rehabilitation. Because [retinopathy of prematurity] ROP is also very much...coming up. Especially on our part, there it never used to be so much ROP. We never used to many ROP patients. But these days, because of the survival [rates] of neonates, and many other factors like IVF and all these things, prematurity is also increasing. At the same time, it's bringing ROP also. And the survival is increasing. So ROP, I think, is also the next big thing...in ROP, I feel that [we'll see] so many easier treatments. Before there used to be only lasers and cryo, and now Avastin is there. So maybe more, simpler forms of treatment, and at the preventive level, also that will come up. There will be so many things that will make the lives of these visually impaired-children easier in next 10 years to come.

 My final question is the fun one: What are you most looking forward to at this ARVO meeting?

 This is my first ARVO! Though I have been to the US before many times, in APOS meetings and in other times, but for ARVO, it's my first time. I'm really looking forward to so many things about it, because right now I'm involved in research so I will go to all of them–I mean, as far as possible, I'll go to all the lectures which are of an interest to me...And I'm staying with my friends, so we'll have fun at the same time.

Well, congrats on your first ARVO, and I hope that you have an absolutely wonderful time. Thank you for speaking with me today. I really appreciate it.

New research findings presented at this year's ARVO meeting compare two groups of paediatric patients in Nepal

David A Berntsen, OD, PhD, FAAO, discusses the BLINK2 study

Ahead of this year's ARVO meeting in Seattle, Washington, the Eye Care Network spoke with David A. Berntsen, OD, PhD, FAAO, who is the Chair of the Department of Clinical Sciences, as well as an Associate Professor and the Golden-Golden Professor of Optometry, at the College of Optometry, University of Houston, Texas. He discussed the Bifocal Lenses In Nearsighted Kids (BLINK) Study and results from the BLINK2 Study, the latter of which he is presenting at the ARVO meeting. 

- This transcript has been edited for clarity.

 Hi, my name is Hattie Hayes, and I'm the editor of 

. This year's ARVO meeting is in Seattle, and we're speaking to some of the attendees about what they're presenting at the meeting, what they're most looking forward to, and the exciting data that we're going to be able to talk about after the conference. 

Joining me today I have David Berntsen. We're going to be speaking about his presentation, which focuses on axial length growth after discontinuing soft multifocal contact lens wear in bifocal lenses in nearsighted [kids]. This is the BLINK2 study. So I'm really excited that you're here to speak with me. Myopia management has been a really hot topic recently, and I'm very glad I get to talk to an expert. Thanks for being here.

: Well, to start off, tell me about your ARVO presentation. I'm excited to hear more.

: Sure. So, the BLINK study is funded by the National Eye Institute. It started off as a 3-year randomised clinical trial between my team here at the University of Houston College of Optometry and my collaborators at The Ohio State University College of Optometry where, collectively, we enrolled just under 300 kids across both sites and randomly assigned them to wear either standard single-vision soft contact lenses, a medium-add centered distance multifocal contact lens, or a high-add center distance multifocal contact lens with the initial question of, first off, do these lenses slow the progression of myopia? And then also, does the power of the lens that add power matter? Does do you need to have that higher add, for example, in order to slow progression? So essentially, what we found is that, yes, the lenses do work, but you do need to use, at least in the design that we were using, you need to use the highest add power. 

We found an effect there where we did find slowing of eye growth, and then also found slowing of myopia progression. So then, bring in the BLINK-2 study, again funded by the National Eye Institute, where our next questions were really wanting to dig into the mechanisms behind the effect that we found, and also, one of the pressing questions that's out there for any type of myopia control methodology, whether it's an optical intervention or pharmaceutical intervention, is what happens when the child stops using that intervention? There have been certain studies that have shown, for example with atropine, where you can get an actual what looks like an acceleration in eye growth once the child stops using that drop. Of course, for any treatment to be beneficial, we need the effect to stick around after the child stops wearing it. 

So that was a big question that that we wanted to be able to answer with the BLINK-2 to study. So all the children who completed BLINK were invited to participate in the BLINK-2 study, which was another 3 years beyond the the original BLINK study, and all the kids were, for the first 2 years of the study, put into the high-add multifocal lens that we had found slow progression in the original BLINK study. After 2 years of wearing that multifocal lens, we then switched all children into a single vision soft contact lens and followed them for an additional year to look and see what happened to the rate of eye growth, their axial length, and also to look at the myopia progression. 

And essentially what we found, in a nutshell, is that both eye growth and myopia progression did increase slightly, but the amount that it increased is more in line with what you would expect for a child of that age. So while we did see a little bit of an increase, it wasn't a what, sometimes you'll hear called as a rebound, where there's a loss of the treatment effect that has already been accrued. Looking at both refractive error, refractive error was progression over the course of that year in the single vision lens, was just barely under a quarter diopter for the year, and then the growth of the eye the axial growth over that year was about 0.8 millimeters in the course of the year, which again, both of those, if you look at normative growth curves for children wearing standard corrections, those are very much in line with what you would expect. So we were pleasantly, we're happy to see that, in fact, all of the benefits that had been accrued originally from wearing the lenses continue to stick around, and it didn't matter how long a child had been in multifocal lenses. So some of these kids had been in multifocal 's for over 5 years, and some only wore the multifocal for 2 years, because they were in our original control group. All children, it didn't matter if they hadn't worn them for a long time or a short amount of time, we didn't see any difference in what progression look like after kids came out. 

Now, one other key thing I think it's important to note is in this study, these kids were at the time of enrollment into BLINK-2 were older now, at this point. So, they were on average about 15 years of age, which then means, by the time we were taking them out of the lens, they were now on average, about 17 years old. We had some kids who were in college, and we were coming out of high school. So again, this is an older group of kids. So, at least what we're able to talk about is if you keep kids in that long longer amount of time when they get to that older teenage, those older teenage years that appears, at least from these multifocal lenses seems to be an okay time to take them out if you need to without there being any loss of the benefits.

: That's great to hear, and very interesting. I feel like we don't talk about the discontinuing use of myopia treatments as much as we should, especially because with lifestyle changes that kids are going through, it's very much a real thing to consider. So is there anything in these data that surprised you or that you think your colleagues who see your ARVO presentation might be surprised by?

: So for this particular presentation, I think it's what a lot of my colleagues and other myopia researchers would hope that we would see. Because again, for some of the younger kids in some other types of interventions, there have been, there have been these headset rebounds that happen. So this is consistent with another long-term study that used a different design of lenses as well that also found a treatment effect that then kept the kids in for a longer period of time. And when they took them out of those contact lenses as well that study also found no evidence of an acceleration or a rebound or loss of that treatment effect. So from that standpoint, it's a good thing. I would say something that has surprised me, and I think all of my colleagues and probably those outside of our study group as well, from the study, is, I mentioned that we're looking at mechanism as well, "so why do the lenses work?" It's been assumed for quite a long time that the eye is paying attention to the sign of defocus on the back of the eye to help it determine how fast it grows or how slow it grows. 

One of the things that we looked at specifically in this study (and recently just published the results from that, in IOVS [Investigative Ophthalmology & Visual Science] just a few months back), was that we did not find a strong signal in the sign of defocus in determining which kids were going to respond better to the lens. So what that tells us is that we have to modify maybe your thinking a little bit and why the lenses work, because in order for us to optimise a design to maximise that treatment effect, we really need to know the underlying mechanism. So it doesn't appear that it's as simple as the sign of defocus, there has to be something the eyes paying attention to that is being affected by the optics of the lens, whether that be contrast or image orientation or some other aspects. So, there's a little more digging to do. The story, as it seems like it always is, is a little more complex as far as the mechanism of action than than what we initially thought. But it's still, it's still positive to know that the lenses are working. Now it's just a matter of digging in a little bit more to understand the why behind it.

: So you made the classic move of giving yourself more homework—I'm very familiar with that! Well, looking at ARVO more broadly, tell me what you're excited about, whether it's something on the program or just a networking event. I'd love to hear what you're excited about at the event itself.

: So meetings like this are always, just, a great time to get to see a lot of fellow researchers who work in this area and see what the latest things that are coming out from their labs. So as you mentioned, that myopia is kind of exploded as far as the number of people working on this. So, the opportunity to actually see colleagues who I know are working in various different areas across multiple different types of interventions down to the basic science level of trying to understand myopia is really what the exciting part for me is. It's always interesting to see what the new studies are that are coming out. More and more, we're seeing results from longer term studies, which we really need that are being presented, and then also still more mechanistic and new optical designs, new considerations for pharmaceutical treatments and whatnot. 

So really, it's just as as far as the meeting goes, it just really is an energising event because you walk away with new ideas from talking to colleagues and going up to their poster or listening to their presentation. And just being able to bounce ideas off of people who aren't who you are talking to every day, but that you do see, for example, at ARVO every year when you go to see what they're presenting, and they come up to see what you're presenting.

: I think that those long-term studies really represent a massive change on the horizon. What do you think will be the biggest change to how we approach myopia control and myopia interventions within the next 10 years or so?

: Gosh, a lot can happen in 10 years. So, I will say, so in the last 10 years we've seen us go from almost no long-term trials for any type of intervention to now we have long-term trials on various novel spectacle designs, on multifocal center distance multifocal contact lens designs, other novel contact lens designs, and now, very recently, within the last year, there are multiple studies that all came out looking at low concentration atropine to see whether the dose of .01% versus .05%, what happens when kids come out of these interventions as well as stop using these drops? So over the next 10 years, I hope to see some, maybe a little more of a direct path on, for example, atropine. That's one area right now, where there's a lot of, multiple studies have checked in very recently, and they're not all finding the same thing, which makes it a little harder then for someone to know "how do I take this and apply this into clinical care?" 

So I'm hopeful that those types of things will work their way out as we continue moving through, as more studies continue to be done. And then, I'm hopeful that we will learn more about mechanisms because, again, in order to optimise treatments, we really need to understand what the signal is that the eye is paying attention to, and then, from there, see if there [are] ways [to] customise, perhaps, a treatment to an individual child's eye in order to maximise the benefits to them. So I'm hopeful, but I don't think we're going to be all the way there in 10 years, but I am hopeful that we will have made progress on that front, where we can, we have better ideas of who's going to respond best to which treatments. So something else in the next 10 years that I think we'll start seeing more work being done on is ways to delay the onset of myopia or onset of nearsightedness. 

So there have been studies that have already been published, from Asia, looking at whether or not low concentration atropine can delay when a child becomes nearsighted. As we've seen from a lot of studies done in the United States, the results don't always match up across the globe. In these studies, it will be important for studies in the US, as well in Europe, to be done to look and see whether various types of interventions can actually delay myopia onset. If we could delay onset, we can also potentially, then reduce how myopic that kid ultimately becomes, when they're done progressing, when they're older, and perhaps reduce the risk of associated eye diseases that go along with myopia.

: Well, you're making me feel really excited about the future of myopia control. So good job there, you're doing great. I'm getting a little bit more short-term and a little more granular. You know, looking at the weeks after ARVO is done, what advice do you have for an eye care professional be at an optometrist or an ophthalmologist? Who wants to enter the world of myopia management? What advice are you hoping they'll take away from this conference and maybe start using in their own practice right away?

: So what I'd hope is that they see what I think is going to be a broad spectrum of various different types of interventions that are available. For myopia control, there's no one size fits all, not every child is going to be a candidate for a multifocal contact lens, not every child is going to, low-dose atrophine isn't going to be the right solution for every child. There's lots of different things, orthokeratology, for example, that's always not an option for every single kid. But for each child, just knowing recognising the multiple things that are out there, and, in the United States, I'll say this as well, we don't have access yet to the novel spectacle designs that are available, pretty much everywhere else outside of the US, including even our colleagues, north in Canada have access to these, but in the US, we still don't. 

So recognising that there are multiple different options that are there, and just making sure they're aware of those so that when there is a child, and when a child comes in, starting to have that conversation with the parents about, there are options other than standard spectacles. The old mantra of, you know, myopia doesn't have any long-term consequences, so we just we just give them new pair of glasses and update the prescription. I think we've seen a very large mindset shift in what is being done around the world and pushes for what the standard of care should be, which is, when you have a child who's myopic, making sure they're aware of those options, so that the parents are aware, the child is aware, and then finding that best fit. No one solution is going to be right for everyone, so if this is someone who's just getting into the world of myopia management, look at that literature that's out there, go to the conferences where there's opportunities to learn about the different modalities to have an arsenal, essentially, of what can be offered to the parents of a child who is nearsighted. 

And when they become nearsighted, I would say one thing that, very often, I've had plenty of people say, "Well, I'm going to wait a year and see how fast they progress before I decide if they need to be in myopia control." The things that I would that just say that we know from the literature, children progress the fastest, the younger they are when they start they progress the fastest during, right after the onset of myopia. So really looking to see how fast they progress before you do something, you're missing out on a window of opportunity. So, if you're going to offer that, which I hope they will, then do it, offer it, as soon as you see that that kid is myopic.

: That's great advice. Thank you for giving me an exciting entry into the world of myopia control and for giving us advice for anyone who might be watching and curious. I really appreciate it, and thank you for sharing your expertise.

At this year's ARVO meeting, new data from the BLINK2 study show axial growth rates after discontinuing soft multifocal contact lens wear

ARVO 2024: Updates from the BLINK2 study on contact lens wear and axial length growth

At the 2022 American Academy of Ophthalmology meeting, Dr Philip Dockery, MPH, presents, "Effectiveness of corneal crosslinking in young patients."

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Younger patients often require repeat corneal crosslinking, study finds

Prof. Ioannis Pallikaris discusses his 2022 ESCRS presentation: "Peripheral Capsule Reconstruction And IOL Centration With The Fixoflex Ring".

Fixoflex ring: Prof. Pallikaris describes how to utilise the device during IOL implantation

My name is Sally Ong. I'm an assistant professor of ophthalmology at the Wake Forest University School of Medicine as well as an adjunct professor of ophthalmology at Wilmer Eye Institute.

At the Wilmer Eye Institute, we completed a multicentre, retrospective cohort study looking at giant retinal tear related retinal detachments that were surgically repaired with vitrectomy versus vitrectomy and scleral buckling. And we examined surgical, anatomic and functional success between the two groups.

We found that there were really no differences in baseline demographics between the two groups, except for a higher preponderance of patients with developmental abnormalities in the vitrectomy and scleral buckling group versus the vitrectomy alone group.

We also found there were no differences in the use of surgical adjuncts between the two surgical groups. There were no differences in rates of retinectomy, drainage retinotomy, and no differences in the use of surgical tamponade between the two groups.

When we looked at anatomic success rates, we found that there was no difference in single surgery anatomic success at six months or one year between the two surgical groups. The single surgery anatomic success for vitrectomy-only eyes was 77% versus for vitrectomy and scleral buckling eyes, it was 86%.

Next, we stratified the eyes by age. And we found that in children less than 18 years of age, there was a difference in single surgery anatomic success at one year. Specifically, the success rate was higher in vitrectomy and scleral buckling group: it was 89% versus in the vitrectomy-only group, the success rate was 56%.

However, when you looked at adults, there was no difference in single-surgery anatomic success between the two surgical groups.

We also looked at visual functional outcomes. And in adults, again, there was no difference in visual outcomes at one year between the two surgical groups; however, in children, there was a difference in the two surgical groups. Visual outcomes were better in the vitrectomy and scleral buckling group, versus vitrectomy-only group for children.

So in conclusion, we found that in eyes with giant retinal tear-related retinal detachment, for adults at least, there was no difference in anatomic or visual, functional success at one year between vitrectomy alone versus vitrectomy and scleral buckling. However, in children, we found that anatomic and visual outcomes success was higher in the group that was treated with vitrectomy and scleral buckling versus vitrectomy alone.

And we hypothesize that is because when you have a giant retinal tear, it looks almost like a relaxed retina to me. And that may be sufficient for adults, but in children, where the vitreous is still very formed, having that scleral buckle as an adjunct, it's really helpful to increase your surgical anatomic and functional success.

At ASRS 2022, Dr Sally Ong presented a talk entitled, “Vitrectomy vs Vitrectomy With Scleral Buckling in the Treatment of Giant Retinal Tear Related Retinal Detachments: International Multicentre Study.” Here she shares the biggest takeaways.

Paediatric eyes repair better with scleral buckling, adults need vitrectomy only for giant retinal tear-related detachments 

Dr Fatema Ghasia, director of the Ocular Motility Laboratory at the Cole Eye Institute, sat down with 

executive editor David Hutton to discuss her talk at the 2022 ARVO meeting held in Denver, CO.

Thank you for having me. So the talk was on looking at fixation eye movement abnormalities and how it affects binocular visual functions and amblyopia.

Since we know amblyopia is lazy eye, it affects about 5% of children. And previously, amblyopia was primarily thought to be a problem where vision in one eye is weaker than the other. But recent research has suggested that it has implications on your binocular vision, so the talk was on looking at how fixation eye movement abnormalities differ in patients who have good binocular visual functions versus those who don't.

So in this experiment, what we have done is we specifically measured suppression. So amblyopia is now increasingly thought to be a problem with the suppression of images from the weaker eye. And so there are newer treatments that are coming out that aim to reverse this interocular suppression. And so what we basically found is that if you had certain eye movement abnormalities, and by that I mean, certain forms of nystagmus that are seen, then you're more likely to have poor binocular visual function, as well as possibly can have more interocular suppression.

You know, now, the fact that we realize that, you know, the suppression plays a major role in in amblyopia — so, there are newer anti suppressive amblyopia, treatments — and so if we know of the eye movement abnormalities they have, if you knew ahead of time, it may give us insights into prognosis of the condition and, and also perhaps give us insights into response to treatment.

So, you know, if you had certain fixation, eye movement abnormalities and you have worse, then there is a likelihood that after treatment, your recovery or binocular visual functions may not, you know, be complete in the sense that you can still have improvement in your visual acuity, but your binocular visual functions may not recover completely. I think it would help us understand response to treatment and give us some ideas about the prognosis.

So the next steps would be to continue to, of course, you know, we would like to create a database of amblyopia patients, and kind of understand how fixation eye movement abnormalities can help us better gauge the pattern of visual function deficits that we see.

Amblyopia affects, you know, not just the visual acuity of one eye; it also has effects on contrast, sensitivity, it has effects on your depth perception, we now increasingly recognize the role of interocular suppressions, and we also know that it not only affects the lazy — or the weaker — eye, but it also has effects on the so-called good eye.

What we're trying to ultimately do is do a battery of tests on these patients before treatment, and then kind of follow them as they're doing the more conventional treatments of patching and eyedrops, versus the newer treatments that have recently been implemented, which are dichoptic treatments, which are anti-suppression treatments, and kind of see how fixation eye movements can help us figure out the pattern of visual function deficits that we see because we know that not all patients have all of the problems that I just described.

And so it will kind of help as this missing link between understanding the pattern of visual function deficits, as well as, to kind of see how the visual functions improve with that conventional and newer treatments.

Note: This transcript has been lightly edited for clarity.

The study found that if certain forms of nystagmus that are seen in patients, then there is a higher chance of poor binocular visual function, as well as higher interocular suppression.

Binocular vision affected by amblyopia, research suggests

Dr Carel Hoyng discusses his presentation at the Angiogenesis, Exudation and Degeneration meeting hosted by Basom Palmer. Entitled “Stargardt Disease, Towards Therapy,” Dr. Hoyng’s presentation explored the origins of Stargardt disease, proper diagnosis, current gene therapy trials and RNA therapy options.

Thank you for joining me today, Professor Hoyng, to discuss your presentation at the upcoming Angiogenesis meeting. Firstly, what are the main takeaway points from your upcoming presentation?

The main takeaway points from my presentation are that Stargardt's disease is the most common inherited retinal disease caused by a single gene. However, due to the difficulties of this gene—it's very large, it doesn't fit into an AAV virus—gene therapy until now, has not been undertaken at this moment. No trials in gene therapy.

There are a few trials that have a pharmacological approach by, for example, slowing down the visual cycle, which has a lot of times possible side effects. And we have undertaken now the efforts to make an RNA therapy, which is now called in United States ASO, antisense oligonucleotide, therapy to—with small molecules to repair the RNA. We are now in preclinical phase of research.

That's very interesting and how might the topics from your presentation be applied day to day?

One topic—subtopic—of my presentation, but very important, is that a lot of Stargardt's disease are not recognized properly.

So we know that the traditional picture of Stargardt's disease by a flecked retina and in children, but there is a part of Stargardt's disease that occurs in adults and is not recognized properly always. And is diagnosed mostly as dry AMD, which it is not. It's Stargardt's disease, and we have solved nearly all the genetic mutations in these patients.

So about 1/3 of patients with Stargardt’s disease are late-onset Stargardt's disease and should be recognized as that.

 What are the next steps for this research?

 In our research in where we try to repair the RNA mutations, the next step is that we will go into clinical Phase 1/2, and probably in about a year. And so that are the next steps at this moment. We are in talk studies. And the next step is to go to in-patients.

That's excellent. And finally, what are you most excited about in this field?

 In the total field of inherited disease, I am very excited that therapies are really coming on the market now. So all these kids that get blind by all different kinds of inherited retinal diseases. Now, in the near future, there will be therapies. And that's very exciting. I think one of the most exciting fields at this moment in ophthalmology.

 Indeed. Well thank you very much for that short interview. It was most interesting.

This transcript has been lightly edited for clarity.

Dr Carel Hoyng divulges the main takeaways from his Angiogenesis presentation, including the origins of Stargardt disease, correct diagnosis, ongoing gene therapy trials and the future of therapy.

Paediatrics

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