"Do not dismiss these children": Dr Lotfi Merabet's message on CVI

Cerebral visual impairment (CVI) has become the leading cause of pediatric visual impairment, yet it remains widely misunderstood—a condition in which a child can read the eye chart perfectly and still struggle to navigate a crowded room or cross a busy street. Lotfi Merabet, OD, PhD, MPH, has spent his career working to explain that disconnect, tracing how the brain, rather than the eye, shapes what these children can and cannot see. In this Q&A, he discusses what drew him from ocular blindness to brain-based visual impairment, what his research on motion processing reveals about the neural roots of CVI, where diagnostic tools like neuroimaging and eye tracking are headed, and why he urges eye care professionals never to dismiss these children and their families.

What sparked your interest in neuroscience and in CVI specifically?

Lotfi Merabet, OD, PhD, MPH: I think it's something that has evolved over time. My interest in neuroscience started off initially because I always thought the brain was really the last frontier in terms of what we need to know. I think what's most interesting about neuroscience is that if you study the brain, you're really studying what it means to be human, or what is a really key piece of being human as well. Brain and behavior go together. How does the anatomy determine who we are, and who we are influences tremendously how the brain develops and the anatomy, and so on. So that 2-way relationship to me was always very, very interesting. As I proceeded in my education, graduate school, and my clinical training, and so on, I came across some work that was really, really striking, in particular in the case of blindness. What I came to learn was the part of the brain that's normally responsible for vision: the occipital visual cortex of the brain, which represents an enormous amount of real estate from a neuroscience perspective or a neurology perspective. I became very interested in this idea that that part of the brain becomes responsible for processing non-visual information in blind people; so for example, it is responsive to braille reading. It is responsive to auditory processing. So to me, not only was that interesting from a neuroscience perspective, but it was also interesting from the potential of the brain to change and to adapt in what we call neuroplasticity. So I think that was really intriguing. Over time, my interest from ocular blindness shifted to cerebral visual impairment or brain-based visual impairment, really because of need. It was really quite striking. I came to learn over time that various schools for the blind across the country, not just in the United States but worldwide as well, was seeing this dramatic shift in the profile of their students. You know, traditionally, 40-50 years ago, kids who were enrolled at schools for the blind were typically visually impaired due to an eye-based issue. So they would learn to read braille, they would learn to use a white cane, and so on. And then that changed dramatically over the last few years. And this is indeed the condition called CVI or cerebral cortical visual impairment. So this shift from eye-based visual impairment to brain-based visual impairments was quite dramatic from a public health standpoint. It's now the number 1 cause of pediatric visual impairment, and that's aligned with my interest in plasticity in the brain as a clinician and as a scientist to put it all together.

Your research found that the area hMT+–the part of the brain that processes motion–responds differently in people with CVI than people without it. What does that difference actually look like? What do you want eye care professionals to know about that difference?

Merabet: I think it's intriguing from a clinical perspective, but also from a neuroscience perspective as well, because it's a great example of how studying the brain helps us understand the clinical profile of these individuals. So area MT, which stands for middle temporal area, it's the anatomical location where it is in the brain. It's also called area V5, in depending on what side of the Atlantic that you're on. And this is the part of the brain that's not just responsible for motion, but in particular motion integration (so the way that we process complex motion). So, for example, walking through a crowd or following the general motion of traffic, this is the part of the brain that's responsible for that. The interesting thing is that many kids with CVI tell me, for example, that they have trouble crossing the street or finding their way through a very crowded environment as well. Even though they may have 20/20 visual acuity or intact visual field, their ability to process this complex motion is seems to be very, very difficult for them.

So we did a study looking at that specifically on multiple levels. The first way that we looked at it was using visual psychophysics, and visual psychophysics is a way to study particular aspect of visual perception. In this case, motion processing using highly controlled stimuli, and that was this particular case, what's called coherence. Coherence is the amount of dots that are in a visual stimulus, and they have to move in a certain direction, either moving away towards you or away from you, and the amount of the proportion of dots that moves together is your coherence threshold, your ability to distinguish that motion. And the lower that threshold, the more sensitive your visual processing system is. What we found is that using the psychophysical stimulus in the case of CVI, that threshold was about 3 times higher in CVI, which means that they needed 3 times more signal in order to be able to reliably determine the direction of motion in this in this looming in this forward backward direction. So that was the psychophysical correlate to this clinical profile.¹

We then had these same individuals do the same task in an fMRI scanner, so using a scanning technique that allows us to see what parts of the brain are active in the processing of this information. And what was interesting is that in the early parts of the brain, the primary visual cortex, we found that controls and individuals with CVI showed very similar levels of activation, which told us that the problem wasn't an early processing issue. So it wasn't a question of the information entering the brain, but if you compare that in area MT or area v5, this higher order processing area, we found that activation was much lower in CVI than it was in controls. So I think it's a nice example of how the clinical profile can be investigated in a way in a controlled scientific manner, and then the neural correlates can be investigated using brain imaging to have an understanding of what parts of the brain seem to not be able to do the processing that they should. And again, just to reiterate, it really drives home this idea that it's not about the information entering the brain; it's really about how the information is processed in higher order areas of the brain, and that's a key feature of CVI.¹

You've used brain scans to link physical damage in the brain to the actual vision problems kids with CVI have. Right now, does that kind of scan work to change how a child gets diagnosed or treated, or is it more about building understanding for the future?

Merabet: I would say at this stage, it's really more understanding, as we say, the neural correlates. Trying to understand how the brain activation and brain wiring help us understand the clinical profile of these kids with CVI certainly at this stage, and it's for a number of reasons. One is: the costs associated with brain scans are obviously very, very high. The second issue is it's difficult and it's challenging to develop the analysis pipelines to do this as well. So the cost of the investment in terms of doing this work to try to trickle down from a diagnostic standpoint. It's still quite large. That's not to say that that won't happen in the future, but in the early stages now, I would say it's really more investigational. The second reason why I think that's absolutely crucial is to understand that not every child who has CVI has apparent damage structurally at the level of the brain, and there's some estimates that it's about 30% or so, so it doesn't mean that there isn't damage at the level of the brain. We just simply can't see it with the anatomical imaging that we have right now, and that's an important thing to think about. So certainly, when it comes to diagnosis of CVI, it's going to be largely based on the presentation of that individual, their functional issues, the challenges that they have. They're obviously standard things like their standard ophthalmic examination. So that's really what's going to drive the diagnosis. But the field also needs this extra piece of objective data, going beyond just what the patient reports, or what a teacher reports, or a parent says, or so on.²

So we need these functional assessments, these objective functional assessments. Neuroimaging is certainly one way to do that, but as I said, it's a heavy lift from a cost of time standpoint, and that's 1 reason why our particular lab is pushing more and more towards eye tracking because eye tracking is a way where we can collect that objective data. Because we're essentially studying the eye brain connection, so how the eyes move, where you look, where you don't look, how long you look at something, what you choose not to look to look at, or what you don't notice, tells me something about how your brain processes visual information. This can be done quite readily and quite easily, not only just in a laboratory setting, but also in a clinical setting. I think that's probably a very, very fruitful direction in terms of helping us diagnose CVI without necessarily relying on the heavy lift that's associated with neuroimaging.²

If you had one more message for eye care professionals about CVI, what would it be?

Merabet: I would say the most important thing to keep in mind is: do not dismiss these children. Do not dismiss these families. There are horror stories that I've heard personally with families that I've worked with, where they've gone from eye doctor to eye doctor to eye doctor on their fourth, fifth, sixth pair of glasses, thinking that either this would just simply go away or be fixed with a tweak in the prescription, or the eye doctor simply said, “I looked at the eye and your child reads the eye chart, and maybe this is a psychiatric condition. Maybe your child needs more attention,” something along those lines. And the eye doctor was simply not aware of the eye brain connection, that just because the eye was healthy, or [in] the standard test that we do in an eye exam, the child passed those tests, [and] they were very quick to dismiss that child and the visual challenges that they have. I think the important thing to keep in mind from the visual from the eye care perspective is you can be visually impaired and have 20/20 vision, and that disconnect I think is kind of challenging for a lot of eye doctors to understand, get their head around. I think that's really the message that needs to be perpetuated in the community. That's not to say that everyone should be a CVI expert or diagnose CVI every day. That's not the idea. But what I would ask the community is to not dismiss these children and these families. And as I said, when you see that disconnect between what you measure and what the child is reporting or what the family is reporting in the context of early brain injury or neurodevelopmental disorder, you should be very, very suspicious. And if this is not something that you're comfortable yourself diagnosing, that's completely fine. But you should certainly put them on a path to another eye care provider or another clinical specialist who is willing and and perhaps more experienced with this field to make that diagnosis. Because, like I said, these children are falling through the cracks, and many, many parents have traveled throughout the country to try to find somebody who can kind of put a term and a diagnosis to what their child has. We as a community need to be able to make sure that these children don't fall through the cracks.

References

1. Pamir Z, Bauer CM, Bailin ES, Bex PJ, Somers DC, Merabet LB. Neural correlates associated with impaired global motion perception in cerebral visual impairment (CVI). Neuroimage Clin. 2021;32:102821. doi:10.1016/j.nicl.2021.102821

2. Merabet LB, Mayer DL, Bauer CM, Wright D, Kran BS. Disentangling how the brain is "wired" in cortical (cerebral) visual impairment. Semin Pediatr Neurol. 2017;24(2):83-91. doi:10.1016/j.spen.2017.04.005