CVI: Moving past the eyes and into the brain

White matter reconstruction (shown in sagittal view) of 3 main pathways involved in the processing of visual information, namely, the superior longitudinal fasciculus (SLF) (the neuroanatomical correlate of the dorsal visual processing stream), inferior longitudinal fasciculus (ILF) (the ventral visual processing stream), and inferior fronto-occipital fasciculus (IFOF) (mediating visual attention and orienting). The 3 white matter pathways are reconstructed in (A) in a normal sighted/developed control, (B) in an early ocular blind person, and (C) in CVI in an individual with associated periventricular leukomalacia. The ILF, SLF, and IFOF are fully reconstructed in the control and early ocular blindness. In contrast, the SLF and ILF are sparser, and the IFOF would not be reconstructed in the individual with CVI. These differences in the structural integrity along these major white matter pathways may be related to observed cognitive visual dysfunctions in CVI.2 (Image courtesy of Lotfi Merabet, OD, PhD, MPH. Figure adapted from references 3 and 4).

Reviewed by Lotfi Merabet, OD, PhD, MPH, and Jessie Cronan

Cortical/cerebral visual impairment (CVI), a condition related to brain injury, is visual impairment resulting from damage to the visual pathways in the brain. Unfortunately, CVI is all too common although not frequently diagnosed.

And therein lies the problem.

CVI is the leading cause of pediatric visual impairment and blindness in the United States and developed countries worldwide,¹ according to Lotfi Merabet, OD, PhD, MPH. Merabet is an associate professor of ophthalmology at Harvard Medical School and director of the Laboratory for Visual Neuroplasticity, Schepens Eye Research Institute, Massachusetts Eye and Ear, in Boston. Merabet also is on the CVI Steering Committee of the Perkins School for the Blind in Watertown, Massachusetts.

“There has been a fundamental shift in the clinical profile of visual impairment in pediatric populations, and the Perkins population mirrors this perfectly,” Merabet said.

From the 1950s to the 1980s, children enrolled at Perkins were typically profoundly blind due to a disease or pathology at the ocular level such as infection, inherited disease, or retinopathy of prematurity. Since then, a shift has occurred, with children presenting with a more complex profile. They were visual impaired and often had learning disabilities and motor and/or language issues. The source of those issues was not in the eye but from brain damage, he explained.

“This difference in pediatric blindness is important from clinical and scientific standpoints as well as an educational standpoint,” Merabet said.

Recognizing the source of brain-based visual disabilities is the key to the early intervention in affected children. In light of that, Merabet and other investigators are attempting to determine the inherent differences in these children. Specifically, they want to learn how visual impairment caused by damage to the brain is different from visual impairment at the level of the eye.

Current understanding of CVI

What investigators found is that affected children may have sustained a neurologic complication or brain injury during the time of development, usually at birth or shortly thereafter. Some children may have had a stroke in utero or were born prematurely. Other causes include seizure disorder, trauma, and genetic/metabolic disorders.

Because of medical advances in neonatal care, many more of these children are surviving today. In addition, there is greater recognition of their perceptual and learning issues at the research level. However, the focus today is extending that recognition into the clinics.

In a typical scenario, parents may report that their child cannot locate a favorite toy or cross the street or becomes overwhelmed in crowds or a busy classroom. In contrast, the child’s vision may be only moderately impaired or even normal based on a Snellen chart evaluation or visual perimetry, and the eyes appear healthy on slit-lamp evaluation.

When the clinician does not recognize that the visual impairment is not based on the eye but is localized to the brain, this can lead the parents into the weeds with suggestions of possible diagnoses including autism, development delays, or psychiatric issues.

CVI study

Merabet and colleagues, in collaboration with Boston Children’s Hospital, Perkins, and Boston University Medical Center, are studying the brain scans of children with CVI to correlate any identified structural changes in the brain to the manifesting developmental and behavioral deficits and comparing the scans with those obtained from children with normal vision and those with other forms of ocular blindness.²

In their study, children are divided based on age: 7 years and older and 14 years and older. For the younger group, virtual reality and eye tracking are used to obtain an idea of their visual perceptual abilities by assessing functional vision. In this group, the children are tasked with, for example, finding a certain toy in the toy box or a particular individual in a crowded hallway, and the complexity of the environment and the child’s reaction to it are assessed. As the environment increases in complexity, despite good visual acuity, their vision becomes a very confusing swirl of colors that prevents the differentiation of objects/persons

Merabet uses virtual reality to create functional vision assessment tools that surpass the standard eye chart and tests performed in an ophthalmology or optometry clinic.

“We found that the children are very sensitive to clutter, crowding, complex motion, and, more interestingly, visual demands,” he said. “As the task becomes much more difficult, that is as we make the assessment harder, their visual system breaks down,” he explained.

Although a visual assessment during a standard vision test may indicate that these children have normal visual acuity, when put into a situation in which the visual system is taxed, that is the point at which the system can break down and the hidden visual impairment manifests.

“This breaking down of the visual system in the setting of high visual demands and complexity is the telltale sign of CVI and highlights the difference between visual function and functional vision,” Merabet said. “We need to gain a better understanding of how these children use their vision in the real world.”

The children younger than 14 years undergo an MRI of the brain to see how their brains are wired (ie, white matter connectivity) and activate as a function of performing virtual reality tasks.

“We found that their brains are very different from children with typical neurologic development and from those who are blind from other causes, emphasizing the need for education,” Merabet said.

Also being investigated is why some children benefit from intervention and others do not and how to define the timeline of improvement. Part of the challenge is determining how the cause of the CVI—brain injury, trauma, infection, seizure, or a genetic or metabolic disorder—relates to underlying visual impairment.

“This makes for a complicated patient profile, and every child is unique in terms of their challenges,” Merabet said.

Intervention and beyond

No specific treatment exists for CVI. Early diagnosis of brain-based visual impairment and implementation of strategies to promote maximal brain development are the current focus, but there is no strong evidence yet to support what does and does not benefit these patients.

According to Merabet, this poses a great challenge because much more than vision can be involved.

“It is important to use a multilevel approach that does not just consider vision but also language and increasing cognitive function and self-awareness in general,” he said. “The goal is to promote as much brain development as possible.”

In his laboratory, the investigators attempt to develop novel assessment tools and compensatory strategies to better understand the difficulties that the children face and work around these challenges.

Perkins CVI protocol

Perkins created the CVI Center at Perkins to bring investigators, educators, medical professionals, and parents together to make a concerted effort to recognize the brain impairment in these children as quickly as possible and ensure they have access to the effective interventions they need, while also driving groundbreaking research in the field.

At Perkins, the resources are being focused on how to assess and educate children with CVI and how this disorder is fundamentally different from children with eye-based visual impairment. Fifty-two percent of the students at Perkins have CVI.

Jessie Cronan, senior director of Perkins CVI Now, described a an ambitious 2-part effort spearheaded by Perkins. The initial phase was released in May 2022.

“The protocol is a ground-breaking digital assessment tool that was created out of a series of symposia with leaders in CVI that convened beginning in 2018,” she described.

The collaboration among the experts highlighted the huge gap that exists around CVI knowledge and diagnosis and that it is a problem approaching epidemic proportions largely unknown even by experts in visual impairment. The challenge identified is 2-fold: providing both education about CVI and functional baseline assessments and diagnostic tools for families, teachers, and physicians, she explained.

This recognition generated the Perkins CVI Protocol, which fills the education gap and provides a database of information to support educators and physicians in the US and worldwide.

“The teaching and diagnostic assessment tool that was created has enough embedded educational resources for educators to learn about the disorder, easily accessible, and sufficiently well-structured to be reliably valid and useful for those with all levels of understanding about CVI,” Cronan explained.

This tool is designed to provide more of a whole-child diagnostic assessment of CVI than previously available and to identify children who previously may not have received a diagnosis.

Part 1 is an anonymous data medical review that compiles all the basic information about each patient and facilitates amassment of demographic information in the database that can be shared with investigators.

From this database, a lengthy list of questions was compiled to be used with parents. The questions focus on 16 visual behaviors, resulting in a functional visional assessment (customized student sketch) of the patient’s visual behaviors, what the experienced behaviors may mean, and recommendations for that patient.

The tool includes links to videos/articles about the visual behaviors and scientific reports, tutorials, and lists of online learning courses.

This part also generates a letter to be sent to patients’ eye care providers to include them in the assessment of possible CVI to access care.

Part 2 is an education road map that is under development and validation and is expected to be rolled out in early 2023. It will incorporate everything from part 1 and create a series of recommendations for observations and direct assessments that will generate an in-depth report and provide a set of educational recommendations.

“This report will inform independent educational plans that are core to special education,” Cronan explained.

“The goal is to identify and diagnose [CVI in] these children earlier and follow them closely to obtain the best benefit,” Merabet concluded. “Identifying them when they are in their teens may mean that valuable time has been lost, although it is never too late.”

Lotfi Merabet, OD, PhD, MPH

E: lotfi_merabet@meei.harvard.edu

Merabet has no financial interest in this subject matter.

Jessie Cronan

E: Jessie.cronan@Perkins.org

Cronan is an employee of Perkins School for the Blind.

References

1. Bennett CR, Bauer CM, Bailin ES, Merabet LB. Neuroplasticity in cerebral visual impairment (CVI): assessing functional vision and the neurophysiological correlates of dorsal stream dysfunction. Neurosci Biobehav Rev. 2020;108:171-181, doi:10.1016/j.neubiorev.2019.10.011Martín MB, Santos-Lozano A, Martín-Hernández J, et al. Cerebral versus ocular visual impairment: the impact on developmental neuroplasticity. Front Psychol. 2016;7:1958. doi:10.3389/fpsyg.2016.01958

2. Bauer CM, Heidary G, Koo BB, Killiany RJ, Bex P, Merabet LB. Abnormal white matter tractography of visual pathways detected by high-angular-resolution diffusion imaging (HARDI) corresponds to visual dysfunction in cortical/cerebral visual impairment. J AAPOS. 2014;18(4):398-401. doi:10.1016/j.jaapos.2014.03.004

3. Hirsch GV, Bauer CM, Merabet LB. Using structural and functional brain imaging to uncover how the brain adapts to blindness. Ann Neurosci Psychol. 2015;2:5.

4. Hirsch GV, Bauer CM, Merabet LB. Using structural and functional brain imaging to uncover how the brain adapts to blindness. Ann Neurosci Psychol. 2015;2:5.