Cerebral Visual Impairment (CVI): Important Challenge for Neonatology

June 2025

Cerebral visual impairment (CVI), a disorder of higher order visual function and the leading cause of pediatric visual impairment, is related to neonatal events in the majority of cases (see later). Detection of the neonatal origins of CVI now seems possible with the advent of advanced MRI methods (see later). The current challenge for the neonatologist is identification of the brain pathology likely to lead to CVI, to enable early detection and institution of rehabilitative strategies.

Introduction

This Commentary was stimulated by recent summary reports from an NIH Workshop and from the American Academy of Pediatrics^1,2 and several recent clinical studies concerning CVI (see later). CVI is a relatively common, though often overlooked, sequela of very preterm birth and of neonatal hypoxic-ischemic encephalopathy (HIE) (see later). With recent insights into the pathology and pathophysiology underlying CVI, detection of the neonate likely to exhibit the clinical features of CVI later in infancy may be possible in the newborn period. Such detection could lead to early identification of the affected infant; careful, targeted surveillance; and, importantly, early institution of rehabilitative measures.

Clinical Manifestations

The fundamental disturbance in CVI involves functional vision but not necessarily visual function (e.g., visual acuity).^1,2 Thus, routine visual screening may not identify the brain-based visual impairment in young children with CVI.² The principal clinical features of CVI include apparent disinterest in locating and sustaining visual focus on objects, delay in responding to a visual stimulus, difficulty processing simultaneous visual information and, thus, understanding the “totality of a scene,” difficulty interpreting complex visual objects or surroundings, difficulty recognizing objects or faces, preference for bright colors, difficulty determining where to direct attention when presented with competing visual stimuli, difficulty with spatial awareness and spatial relationships, and such unusual visual behaviors as not looking at an object when reaching for the object (eccentric viewing).^1,2 Similarly, a detailed 48-question CVI inventory reported by Macintyre-Beon et al.³ is focused on questions seeking evidence for impaired visual attention, impaired perception of movement, difficulty handling the complexity of a scene, impairment of visual guided movement of the body, visual difficulties associated with crowded environments, and difficulties recognizing specific people, facial expressions, colors and shapes.

Importantly, in addition to the difficulties engendered by these visual functional impairments, these deficits have deleterious consequences on cognitive, communicative, educational and social development.^1,2,4 To be emphasized later, earlier identification and interventions concerning the functional visual deficits will enhance social and educational development. Thus, early diagnosis and targeted interventions are crucial.^1,2

Pathophysiology

A series of recent MRI and anatomical studies have elucidated the principal anatomical regions and the functions thereof involved in CVI.^1,5-8 To facilitate understanding of the principal disturbances in CVI, first I will review briefly the normal anatomy and function of the regions involved.

Normal Anatomy and Function

Concerning the normal anatomy and function, the areas of particular interest are white matter fiber tracts emanating initially from occipital cortex.^5-8 These consist principally of the superior longitudinal fasciculus, extending through parietal and frontal white matter to the respective frontal and parietal cortices (the “dorsal stream”), and the inferior longitudinal fasciculus, extending through inferior parietal-temporal white matter to inferior-temporal cortex (the “ventral stream”). Multiple connections between these streams are now recognized. The dorsal stream is particularly affected in CVI, and disturbance of this stream is manifested by difficulties with visuospatial attention, processing simultaneous visual information, sustaining and selecting visual attention, and visual searching, among others. Involvement of the ventral stream in CVI may also occur and, as one might expect from temporal involvement, is manifested by impaired visual memory, e.g., recognition of objects, shapes, texture, patterns.

Anatomic Disturbances in CVI

Concerning the loci of the anatomic disturbance in CVI, the best insights have been provided by studies utilizing advanced MRI techniques.^5-8 Thus, measures of fractional anisotropy, radial and axial diffusion, connectivity, and functional integration suggest that the principal disturbances involve myelin sheath, axonal structure and axonal function/connectivity. (Very recent work also suggests that disturbed thalamic volumetric development occurs,⁹ but whether the thalamic involvement is primary or secondary to trans-synaptic disturbances related to the cortical abnormalities caused by the impaired cerebral white matter fasciculi just discussed currently is unclear.)

Neuropathology

Although the pathophysiologic and anatomic data, as just discussed, indicate that specific white matter tracts are the principal areas involved in CVI, the specific neuropathologies affecting these tracts have not been determined conclusively. However, available data provide excellent clues. Of particular importance in this context, multiple studies have shown that perinatal disorders account for the majority of definable pathologies underlying CVI. These disorders principally involve either very premature infants or term infants with hypoxic-ischemic encephalopathy (HIE).³ However, prospective neonatal neurological data with modern imaging for either of these two principal neonatal neurological groups are not available.

Very Premature Infants

Concerning very premature infants, CVI is a considerably more frequent outcome than generally recognized. For example, a prospective study of 46 prematurely born (24 to 36 weeks gestational age [median, 31 weeks]) primary school children showed behaviors consistent with CVI (with a pattern similar to dorsal stream dysfunction) in 33%.³ A recently reported, prospective study of a national cohort (n=225) of very low birth weight (mean gestational age, 29 weeks) young adults (26-30 years), assessed for visuospatial skills, showed impairment in 43%, with 20% exhibiting severe impairment.¹⁰ (More detailed assessment for CVI was not reported.) Moreover, systematic neonatal imaging data were not available.

The best data indicate that cerebral white matter injury is the principal neuropathology underlying CVI in premature infants. The most detailed retrospective studies of pronounced CVI in former premature infants by advanced MRI techniques have been based on subjects who had the neonatal diagnosis of “PVL” and “spastic diplegia,” the latter the classical clinical hallmark of severe “PVL,” i.e., cystic PVL.^5,9,11,12 Diffusion-based and connectivity MRI showed findings consistent with impaired myelination in the fasciculi involved in CVI (see earlier), as well as impaired axonal development (decreased branching, packing density, and axonal diameter). This constellation of findings is entirely consistent with the dysmaturation sequence identified previously in premature infants by neuropathology and advanced MRI (diminished pre-oligodendroglial sheathing of axons with resulting impaired development of myelin, axons and cerebral white matter tracts¹³). Importantly, this dysmaturation sequence of cerebral white matter in very premature infants occurs most commonly in the absence of “cystic PVL”^13,14 and in the presence of considerably less severe white matter injury.¹³ Currently, “cystic” cerebral white matter injury accounts for 5% or less of white matter injury in premature infants. Approximately 20-25% exhibit noncystic disease with punctate white matter lesions, and an additional proportion, still to be determined, have noncystic, non-necrotic white matter disease.^13,14 It appears highly likely that these large latter groups of cerebral white matter injury underlie the high frequency of CVI in very premature infants without major motor deficits in the large-scale clinical studies of CVI described earlier. Clearly, however, the neonatal imaging correlates of later CVI remain to be fully established. Herein lies a very fertile area for future clinical research.

Neonatal HIE

Concerning the second major neonatal group associated with later CVI, neonatal HIE in the term infant, the imaging correlates remain to be determined. Two retrospective, selected series identify apparent HIE as the etiology in 35-50%.^15,16  Assuming the posterior-central and posterior-temporal fasciculi are involved in this group, as in other examples of later CVI, I suggest that those infants with HIE with parasagittal cortical-subcortical white matter lesions, i.e., “watershed” injury, and/or punctate white matter lesions, are most likely to develop CVI. These two lesions characteristically are more prominent in posterior than in anterior cerebrum^14,17 and occur, respectively, in approximately 25% and 20% of infants with HIE in large studies.^18-21 (The small group of infants with “severe” or “global” injury [basal ganglia, thalamus, etc.] are candidates for later CVI, but other major neuro-cognitive deficits may dominate the clinical picture.)

Challenges for the Neonatologist

In my view, the principal challenge for the neonatologist is to identify in the neonatal period the infant most at risk for subsequent manifestations of CVI. Identification of such infants could alert the follow-up team to focus on those visual functional parameters identified earlier as the features of CVI. Conventional follow-up, focused principally on visual acuity (visual function), is likely to miss the impairments of functional vision described earlier. Although still early in evolution, early identification of the features of CVI and interventions targeted for the specific visual deficits described earlier appear promising to ameliorate many of the specific deficits and to enhance development of cognitive function, social-communicative abilities and socialization.^1,2,22

Neonatal identification of the infant at risk for CVI should begin with recognition of the likely clinical circumstances to result in the later manifestations of CVI. As discussed earlier, cerebral white matter injury in the premature infant and HIE in the term infant (especially with parasagittal cortical-subcortical white matter lesions and/or punctate white matter lesions) are the principal clinical settings of importance. A particular focus on the white matter tracts involved in CVI is critical. Application of diffusion-based measures, tractography and, where available, connectivity will be important.

Early identification of the likely anatomic substrate can guide enhanced measures to detect the clinical features of CVI on infant follow-up. Early detection of CVI is especially important in view of the rapid development of the visual system, in terms of axonal outgrowth, myelination and synaptogenesis, in the first two years of life.^23-27 This period is one of especially exuberant plasticity, and, thus, interventions capitalizing on this developmental epoch provide an excellent opportunity to ameliorate the clinical consequences of CVI.

Joseph J. Volpe, MD

Department of Neurology, Boston Children’s Hospital

Bronson Crothers Professor of Neurology, Emeritus, Harvard Medical School

Boston MA

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