Cerebral visual impairment is a growing concern in pediatric vision loss

Image by Jennifer Toomey / MJH Life Sciences using AI

Reviewed by Lotfi Merabet, OD, PhD, MPH

Cerebral visual impairment (CVI) is a disorder caused by damage to the parts of the brain that process vision. It is most common in infants and young children but can continue into adulthood.

A child with CVI has vision problems caused by their brain that are not attributable to an issue with their eyes. Usually, the eyes send electrical signals to the brain, and the brain turns those signals into the images seen. If an individual has CVI, the brain has trouble processing and understanding these signals.

CVI is a leading cause of vision loss among children in the US. For some children with CVI, vision may improve over time, but every case is different. If a child has CVI, they must receive early intervention, therapy, educational support, and other specialized services to help them develop and learn.

Lotfi Merabet, OD, PhD, MPH, of Mass Eye and Ear and Harvard Medical School, both in Boston, Massachusetts, recently served as cochair of a National Eye Institute (NEI) initiative to promote research in CVI. During an interview with Ophthalmology Times, he noted the 3 main objectives of the recent NEI workshop.

“The first is to raise awareness…of cerebral/cortical visual impairment, or CVI. [The] second is to establish a series of definitions and diagnostic criteria that we can use for the care of individuals with CVI,” he said. “The third main initiative would be to establish a national registry that will be important for identifying children or individuals with CVI and characterizing their clinical profile, the diagnostic criteria that were used, and following these individuals over time to get a sense of the natural history of the condition as well.”

Shefa Gordon, PhD, associate director for science policy and legislation at the NEI, detailed how the NEI incorporated CVI into its strategic plan and the steps taken to achieve those goals. He noted that the NEI issued a request for information on topics of interest in the NEI Strategic Plan.

“The CVI community organized a concerted response, flooding the inbox, comprising two-thirds of the 252 individual responses,” Gordon said. “Based on input from scientific planning panels, particularly in the areas of neuroscience and rehabilitation/quality of life, the NEI identified CVI as a major research gap and outlined research opportunities in the Strategic Plan released in 2021.”

Gordon noted 3 issues that emerged: lack of provider awareness/training, development of diagnostics, and development of effective rehabilitation/interventions.¹

“CVI was featured prominently in the Biology and Neuroscience of Vision, Data Science, and Individual Quality of Life Areas of Emphasis in the Strategic Plan, demonstrating the need for research on CVI that encompasses everything from a basic understanding of CVI development to the assessment of therapeutic interventions,” Gordon added.

Recognizing that CVI diagnosis and care require multidisciplinary coordination, the NEI partnered with the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development to create a CVI Working Group and hosted the Trans–National Institutes of Health (NIH) CVI Workshop: Roadmap to Consensus and Building Awareness.²

“The hybrid workshop was videocast—invited participants included ophthalmologists, optometrists, pediatricians, neurologists, research scientists, individuals with CVI lived experience, caregivers, teachers for the visually impaired, occupational therapists, and advocates,” Gordon explained.

Gordon noted 3 workshop goals: to build awareness, develop a registry, and promote consensus. “During the workshop, a panel of clinicians developed a working definition to diagnose CVI,” Gordon concluded. “This definition is in press, to be published in the December 2024 issue of Ophthalmology. The development of the definition is a significant step forward for the CVI community. It affords visibility to this disease while ensuring that researchers and clinicians across neurology, pediatrics, and vision are all speaking a common language, a necessity for the development and use of the CVI registry.”

Merabet said he believes the NEI initiative is vital because CVI is a complex and multidisciplinary field, not just in terms of understanding the basis of the condition but also in terms of diagnosis, education, and rehabilitation. “My hope is that this initiative will bring together not only eye care providers but get other health care providers involved as well,” he explained. “At the same time, vision, developmental, and neuroscientists can help us develop a better understanding of the underlying neurophysiology of the condition, and bringing in other allied specialists, such as teachers of the visually impaired, occupational therapists, physical therapists, [and] orientation and mobility specialists, will also be crucial to advance our understanding of CVI.”

According to Merabet, helping individuals with CVI requires a multidisciplinary approach, not just in terms of diagnosis but also in understanding the underlying basis of the condition and developing educational and rehabilitative strategies. Public awareness and education play a key role in the success of the NEI initiative, and Merabet said there is a fundamental shift in terms of visual impairment and blindness in pediatric populations.

“If you consider visual impairment and blindness in adults, typically, we’re talking about acquired diseases or issues that happen later in life, particularly at the level of the eye,” he explained. “When we’re talking about visual impairment and blindness in children, we’re more focused on something happening early in development, if not at birth, and affecting the brain as opposed to the eye.”

Moreover, Merabet noted that from an epidemiological standpoint, it is important to realize that CVI is the main cause of visual impairment in children, representing a shift in mindset. “The reason behind this is that many of these children are born with some sort of complication occurring at birth or shortly thereafter,” he said.

Merabet noted that 30, 40, or 50 years ago, these children were not surviving severe birth complications, but today they are because of advances in neonatal care and improved recognition. Wwe need to be prepared for these children as they grow older and to ensure they can thrive to their fullest potential,” said Merabet.

Merabet also noted that diagnosing CVI is challenging because no universal protocol or diagnostic algorithm has been formulated. “A lot of that has to do with regional differences in approaches, not just in the United States but around the world. At the same time, there is tremendous heterogeneity with regard to the clinical profile of the condition as well,” he explained.

“Individuals with CVI are very diverse in their clinical presentation,” Merabet continued. “For example, some may have associated eye issues, such as strabismus or significant refractive error, which [have] to be treated. Other individuals may have extensive brain injury, which can affect their visual functioning, such as visual acuity. Others may have brain injury or maldevelopment limited to higher-order areas or processing stages of the brain, [whereas] visual field and visual acuity functions are at normal levels, and thus their visual impairment is more related to the processing of visual information.”

As a result, developing a diagnostic algorithm that can account for this broad heterogeneity is extremely challenging. Merabet said that another issue is developing appropriate assessment tools, which must be feasible and deployable within typical clinical settings.

“I think we have to find some sort of lowest common denominator that allows us to try to catch as many of these individuals as possible so that 1 clinician who diagnoses CVI in 1 part of the country uses the same assessment strategy as someone else would in another part of the country,” he said. “And again, the important thing is that we’re all trying to talk about the same patients.”

Emerging technologies or research methodologies may also hold promise for improving the understanding and treatment of CVI, and Merabet said the clinical research community is considering many methodologies.

“One is using eye tracking, and there are a number of labs in the United States that are doing this,” he said. “I think eye tracking is extremely useful because it allows for an objective characterization of how [individuals use] their eyes and vision when interacting with the world. At the same time, it doesn’t require a verbal or a manual response, which may not always be possible in these patients. So, analysis is based solely on eye movement behavior. That is a very robust feature, and [there are] a lot of data that can be extracted from eye tracking studies.”

Merabet said analyzing where an individual looks, how long they look, and where they do not look can tell us something about how they process visual information and interact with the visual world.

Melinda Chang, MD, assistant professor of clinical ophthalmology at Keck School of Medicine of USC in California and co-chair of the NEI CVI workshop, agreed that eye tracking is a very promising method for improving understanding of CVI.

“Eventually, I believe eye tracking will help us design individualized therapies for patients with CVI,” she said. “It will also help us identify medical treatments for CVI since it can be used as an outcome measure in clinical trials to assess improvements in visual function. Finally, we have some preliminary data that suggest eye tracking can be helpful for prognostication in CVI.”

Chang added that another technology she believes will be helpful in CVI research is artificial intelligence (AI).

“AI can help us interpret large volumes of data and identify patterns that are not immediately obvious to humans,” she said. “We have already used AI to help with the interpretation of eye-tracking data.”

Chang said she is excited about the possible applications of AI to analyze the data that will be collected in the NIH CVI Registry.

“For example, unsupervised AI techniques may help us categorize different subtypes of CVI that respond to different types of interventions and have different prognostic implications,” she said.

A third area to be explored, according to Merabet, is virtual reality (VR).

“I think it’s extremely important because of the complexity of the functional profile of the condition, which is very diverse,” he pointed out. “VR allows us to model the environment in a very controlled way and gives us the opportunity to test vision-related behaviors in a very consistent, standardized, and reproducible fashion.”

Merabet said that VR can be used for testing and rehabilitation and that it provides real-time feedback that can aid in teaching individuals with CVI new ways to interpret visual information. He said it allows an experimenter to create well-controlled, naturalistic environments. For example, it is possible to assess how an individual would search for a favorite toy in a room or find an individual in a crowd. Researchers can observe the effect of manipulating task difficulty, such as by varying the visual clutter of the environment.

“We need to go beyond what we do in a classic eye exam and try to better understand how a person uses their vision in the real world,” he said. “And I think virtual reality could be a promising platform to allow that.”

The initiative will support research on developing rehabilitation strategies for patients with CVI. Merabet said that further research can improve understanding of the underlying neurophysiological basis of CVI and which rehabilitative strategies are most promising.

“For example,” he said, “understanding how a particular type of brain injury—or the timing, location, and extent of that injury—correlates with a patient’s visual function and functional vision would be extremely important because once an individual presents with a particular profile of brain injury or cause of CVI, we can make predictions about how that individual might use their vision, the challenges that they may face, and what could be helpful. At the same time…as an important research initiative, understanding the longitudinal and natural history of CVI is extremely important as well.”

Merabet pointed out that if we can make associations between the cause of CVI and the resulting clinical profile, we may be better positioned to recommend appropriate rehabilitative strategies.

“So, I think it’s extremely important to collect data on a large scale and in an objective manner so that we have a better understanding of the natural history of this condition—something that we have not had in the past, unfortunately,” he said.

Merabet added that every eye care provider has probably seen a child with CVI at some point and may not even realize it. “A patient who presents with normal visual acuity and healthy-looking eyes yet reports all these complex visual issues—like they can’t cross the street safely or have trouble following what’s happening in a classroom—should not be dismissed,” he said.

CVI is not a psychological or psychiatric issue; it is a brain visual processing issue.

“I would tell my colleagues it’s extremely important to remember that an individual with eyes that look healthy and visual acuity within a normal range can still be visually impaired,” he concluded. “There is a visual processing piece that may be impaired because the eyes are connected to the brain, and understanding how the brain contributes to that visual impairment is extremely important.”

Lotfi Merabet, OD, PhD, MPH

E: Lotfi_merabet@MEEI.harvard.edu

Merabet is an associate professor of ophthalmology at Harvard Medical School and an associate scientist at Massachusetts Eye and Ear.

References

1. National Eye Institute. National Eye Institute Strategic Plan:Vision for the Future, 2021-2025. November 2021. Accessed October 14, 2024. https://www.nei.nih.gov/sites/default/files/2021-12/NEI-StrategicPlan-VisionForTheFuture_508_edit.pdf

2. Trans-NIH CVI workshop. National Eye Institute. Updated November 14, 2023. Accessed October 14, 2024. https://www.nei.nih.gov/events/cvi-workshop