Disease Entity

Cerebral visual impairment (CVI), is defined as vision loss resulting from damage to retrogeniculate
pathway, in the absence of any ocular pathology, with increased survival of preterm babies and better
perinatal care, CVI has emerged as one of the leading cause of visual impairment. Other causes of
visual impairment reported in children with multiple disabilities may be secondary to ocular defects
such as uncorrected refractive errors, cataract, nystagmus, retinopathy of prematurity (ROP), optic
nerve atrophy and delayed visual maturation (DVM). The prevalence of CVI in childhood has been
steadily rising over the past few decades from a reported incidence of 36 per 100,000 in the late 1980s
to 161 in 100,000 in 2003.[1][2]

Disease
The term, cerebral visual impairment is preferred to cortical blindness as the central nervous system is
still plastic and presence of extra-geniculostriate visual pathways precludes total loss of sight, even
when there is complete destruction of the striate cortex.

Cerebral, is preferred over cortical owing to the subcortical involvement of optic radiations in
premature infants. The sequelae of perinatal injury are also related to the timing, degree, duration, and
mechanism of damage to a child’s brain. Management of children with CVI requires a combined and
coordinated effort of ophthalmologist, neurologist and rehabilitation services.

Etiology
CVI is commonly defined as a loss in visual function in the absence of damage to anterior afferent
visual pathways or ocular structures. CVI has multiple causes but the most common is perinatal
hypoxia. CVI can result from the insults at level of:

1. Cortex, which includes geniculo striate lesions.

2. Subcortex, which includes focal white matter lesions resulting to periventricular leukomalacia.
3. Delayed visual maturation can also result from a temporary dysfunction of higher cortical
centers.

Pathophysiology
Hypoxia

Hypoxic-ischemic brain injury is, by far, the most common cause of pediatric CVI. [3]The resulting
pattern of injury is due to hypoxia, is mainly, defined by age at which the insult occurs and differs in
term and preterm children. In term infants, the areas between the circulation of anterior and middle
cerebral arteries and medial and posterior cerebral arteries are the most typically affected as they are
watershed areas of the cerebral cortex. Loss of vascular flow autoregulation induced by hypoxia leads
to hypoperfusion of these watershed territories, resulting in infarction of the frontal and parieto-
occipital areas. Striate cortex is affected frequently, associative occipital visual areas and temporal and
parietal cortices, are also involved commonly. Preterm neonates, on the contrary rarely suffer
parasagittal infarctions from hypoxia-ischemia. Periventricular deep white matter is involved when the
insult occurs earlier, between 24 and 34 weeks of gestation. There is a transient, susceptible watershed
zone in the periventricular white matter that later is replaced with the adult vasculature. Periventricular
arterial end zone of long penetrating vessels derived which are mainly from the middle cerebral
arteries, run from the pial surface and terminate in the deep periventricular white matter. Active
development of this periventricular vasculature occurs during the last 16 weeks of gestation. The
number of short penetrators and anastomoses between the long and short penetrators increases in the
third trimester with a consequent decrease in vulnerable end zones and border zones. Capillaries in this
region are prone to hemorrhage from hypoxia-ischemia.
As a result, of hypoxic insult germinal matrix produces glial and neuronal cells which migrate
eccentrically to populate cerebrum. Immature oligodendrocytes and subplate neurons present around
the ventricles are more vulnerable to ischemia than mature oligodendrocytes located elsewhere, and
this explains the specific location of damage.

Thus resulting in the characteristic feature of periventricular leukomalacia (PVL).

Meningitis

Meningitis and hydrocephalus were considered to be the most common causes of CVI in past.[4] In
more recent series, infections account for 11.8% to 15% of cases of CVI.[5] The occipital cortex is more
susceptible to damage produced by Haemophilus influenzae, and hence, it is the most common
organism causing CVI. Pneumococci, meningococci and herpes simplex virus are other causative
agents, which have been implicated to cause ocular and cerebral visual problems.[6] Onset of visual
impairment typically is late in the course of the infection, and multiple accompanying neurologic
sequelae commonly occur. Different mechanisms by which infection might injure the brain include
thrombophlebitis, arterial occlusion, hypoxic-ischemic damage, venous sinus thrombosis and
hydrocephalus.

Hydrocephalus

Hydrocephalus affects vision by causing optic atrophy through various mechanisms, and can also affect
posterior visual pathways which run close to lateral ventricles. A combination of anterior and posterior
visual involvement is frequent. Although ventricular dilatation can occlude the posterior cerebral
arteries, chronic distention of posterior cortex is a frequent mechanism by which hydrocephalus causes
CVI. It is well known that shunt malfunction can cause CVI, but paradoxically, rapid correction by
shunting also occasionally can produce CVI.

Trauma

Head trauma is another cause of pediatric CVI (approximately 4% of cases as reported in two studies).
[7]
Damage may be transient or permanent. Shaken baby syndrome is a common cause of posttraumatic
CVI. Transient vision loss in children can also occur after trivial injuries and is accompanied by
headache, confusion, drowsiness, vomiting, and seizures.

Epilepsy

Epilepsy chiefly, infantile spasms can result in central visual inattention. Pathogenesis of visual
impairment in patients who have infantile spasms is unknown. Anticonvulsants also are known to cause
visual problems.[8]

Congenital brain malformations (lissencephaly, schizencephaly, holoprosencephaly), metabolic and

neurodegenerative disease, hypoglycemia, hemodialysis, cerebrovascular accidents, and brain tumors
are among other reported causes of CVI.

Diagnosis
Ocular features
Visual Function

Visual impairment in CVI can be as severe as no light perception to normal visual acuity. Cognitive
visual function may be impaired in most of these children leading to misinterpretation in relation to
what objects are there and where they are. Vernier acuity has been found to be more affected than
grating acuity. There is some evidence that dorsal stream magnocellular pathway deficits may be more
common in children with CVI.

Refractive error

Children with PVL frequently have hypermetropia in combination with astigmatism. Hypermetropia is
a common refractive error in children with cerebral palsy and can be due to accommodation
dysfunction

Strabismus and Ocular Motility

Infantile exotropia is more common as compared to esodeviation in patients with cortical visual loss.
On the contrary children with PVL present with esotropia commonly and needs to be differentiated
from infantile esotropia.

A specific trait of strabismus in these patients is dyskinetic strabismus, where esotropia changes to
exotropia on a momentary basis. Repeated evaluation and constant deviation measurements are thus
crucial before planning any surgical intervention for strabismus. Nystagmus is a common feature and
indicates subcortical rather than cortical damage and may also be associated with concomitant anterior
pathway diseases, such as optic nerve or retinal disease.

Optic disc features

Optic atrophy is common and can be secondary either to hypoxia involving the optic nerves. In cases of
hydrocephalus, resulting in papilledema may lead to secondary optic atrophy. In a study done by V.
Khetpal et al,[7] optic atrophy was found to be a feature in 40% patients of cortical visual loss.

Visual fields

CVI patients have bilateral inferior field defects most commonly, homonymous hemianopia can also be
present in association with hemiplegia and can be explained by interruption of axons of optic radiations
and partly by the problems of simultaneous attention in them.

Systemic features
CVI can typically be associated with neurological deficits including cerebral palsy, mental retardation
and hemiparesis, microcephaly, hearing problems, abnormal mental development, behavioral problems,
myelomeningocele, progressive degenerative disorders, and hypotonia are among the reported
anomalies, indicating that the damage may not be limited to the visual pathways. Some patients may
also have superimposed anterior afferent pathology from optic nerve–related disease.

Visually impaired children have different blind mannerisms like rocking, thumb sucking, head banging,
head flopping, eye pressing, light gazing and flicking their fingers.

Diagnostic procedures
Diagnosis of this entity is of utmost importance in a child with the normal ocular examination.
However, suspicion begins in the immediate neonatal period.

Visual Evoked Response (VER)

In past, investigators heavily relied on findings of VER and EEG for a diagnosis of cortical visual loss,
however, a normal flash VER recording can be obtained even in patients with cortical visual loss and
can be mediated by the extra geniculostriate visual system.

Electroencephalography (EEG)

EEG was once considered to be a valuable diagnostic tool and shows multiple eleptiform waves
originating from occipital lobe.

Neuroimaging

CT and MRI helps to understand the ocular lesions as well as the underlying pathogenesis of CVI, also
provide clues about the prognosis and visual recovery. Extent and location of brain damage is
important. MRI is always recommended in children with low APGAR score. [9]

Neuroimaging evidence of acute brain injury seen on brain MRI with Hypoxia-Ischemia is also
considered as a significant feature as per the recent task force on neonatal encephalopathy. Severity of
visual impairment could be predicted by the clinical severity of HIE shown at birth. Pattern of lesions
on MRI can be broadly classified into 3 categories: periventricular leukomalacia, diffuse cerebral
atrophy and multicystic encephalopathy.

Children with periventricular leukamalacia, encephalic cyst and diffuse cerebral atrophy are very less
likely to improve, and children with mild damage on MRI have a better prognosis.

Management
Some degree of visual recovery is seen in majority of children with cortical visual impairment, the
improvement tends to be gradual over months, although exact mechanism is unclear. Lambert et al
have summarized various theories proposed for the visual improvement and suggest that insult
producing cortical visual impairment may not cause cellular death but interrupts the normal protein
synthesis of neurons thus causing delay in myelination, dendrite formation and synaptogenesis. [10]

It has now been postulated that improvement of sight in patients of CVI is actually a form of delayed
visual maturation.

Medical therapy
Amblyopia management with patching therapy remains the mainstay of management though
compliance has been a major concern. Strabismus and motility evaluation is difficult owing to the
behavioral aspects, yet has to be performed in multiple visits to know about the stability of deviation
which helps decide optimal timing of surgical intervention. Esotropia being more detrimental is an
indication for early surgery. Undercorrection by 15-20% is done usually to avoid consecutive exotropia
over long term follow up, as overcorrection is more common.[11]

The problems in patients of cortical visual loss are not just limited to vision, but are complex. A
multidisciplinary approach is thus, necessary not just for diagnosis but also for management.
Rehabilitation
Rehabilitation services are much more needed, despite of progress in diagnostic methods,
interventional treatments for CVI are still very limited. Rehabilitation support must include an
approach that addresses psychosocial impact on patients and their families. Various active visual
stimulation therapies have been tried for the rehabilitation of patients of cortical visual loss. Light
reflex stimulation is performed in a completely dark and quiet room done by using a flashlight shined
briefly in each eye, pausing 5 s between eyes. performed for 1 min and repeated 30 times per day. The
ability for perceiving object outline can be developed by shining a penlight onto a target in a totally
darkened room for 1 minute. Simple distinct shapes like circles, triangles, or stars either be on white
cardboard with a black image or black cardboard with a white image shown 10 times a day, help the
child to identify shapes, similarly black and white or colorful outline images added to the checkerboard
environment can be used to develop outline perception. Further details can be added in the form of
colors or expression in a circle which helps in developing the ability of the child to see the details
within a configuration.[12] Each child with CVI, hence is likely to have its own unique visual and motor
deficit, necessitating an individualized approach.