Children with visual impairment due to damage to the retro-geniculate visual pathways
constitute an increasing group among visually impaired children in the Western world. The
developing visual system may be affected by malformations arising early in gestation, by
white matter damage of immaturity (WMDI) both in utero and as a sequel to premature birth,
and by asphyxia as well as by cortical-subcortical damage due to perinatal cerebral infarcts in
children born at term. Infections and trauma in the neonatal period may also affect the visual
system. Much of the brain is devoted to vision. Damage causes visual problems ranging from
profound impairment to cognitive visual problems only.
Visual and ocular outcome after pre- or perinatal brain damage depends on localisation and
extension of the lesion, but also on at what stage the developing system was injured. Plasticity
of the brain may modify the functional outcome when the visual system is injured early in
gestation Thus, reorganisation of the visual system by by-passing the lesion in the ipsilateral
hemisphere or maybe by inter-hemispheric reorganisation may take place in the immature
brain. In addition, retrograde trans-synaptic degeneration may affect the appearance of the
optic disc in retro-geniculate lesions occurring during the pregnancy or in the neonatal period
in children born preterm.
Brain imaging techniques
Examination of the newborn infant brain with ultrasound (US) may detect lesions engaging
the posterior visual pathways, but US is an insensitive method to find minor injuries. Later
during infancy and childhood magnetic resonance imaging (MRI) is the most sensitive
imaging modality to detect permanent lesions to the posterior visual system. The paediatric
neuroradiologist thus plays an important part in the identification of children with cerebral
visual impairment. White matter lesions may be further understood and mapped out with
diffusion tensor imaging techniques.
The manifestations of this kind of visual impairment include subnormal visual acuity and
crowding, affected visual field function and associated disorders of higher visual processing.
The principal cognitive visual pathways comprise the dorsal and the ventral streams. The
dorsal stream runs between the occipital lobes, which process incoming visual data, the
posterior parietal lobes, which process the whole visual scene and give attention to component
parts, the motor cortex, which facilitates movement through the visual scene and the frontal
cortex, which directs attention to chosen parts of the visual scene. The ventral stream runs
between the occipital lobes and the temporal lobes, which enable recognition of people and
objects facilitating route finding and serve visual memory. In addition, impaired control of the
eye movements and disordered focusing may further complicate the effective use of vision.
These problems can occur in any combination and severity. Visual function may improve
Cerebral palsy, learning disabilities and behaviour and attention problems are other wellknown
consequences of pre- and perinatal brain damage. Concomitant cerebral visual
impairment is common but often remains undetected, and therefore is not taken into account
when designing habilitation programs for the individual child. Early brain damage may
however cause only visual problems, and often manifests itself as early-onset strabismus. In
these cases, the paediatric ophthalmologist is responsible for identification of children with
cerebral visual impairment, for assessment of visual function, and for initiating habilitation.
The habilitation of these children demands a multi-disciplinary team including paediatric
ophthalmologist, orthoptist, neuropsychologist, paediatric neurologist, occupational therapist,
physiotherapist, low vision teacher and remedial teacher.
Our research team at Karolinska Institutet has in collaboration with researchers from
Gothenburg during the years 1996-2009 contributed to the bank of new knowledge of visual
and ocular outcome in children with pre- and perinatal brain damage.
Prematurely born children with WMDI
Crowding and cognitive visual problems in children with WMDI
In a study of prematurely born children with visual impairment due to WMDI, we described
subnormal visual acuity and crowding (Jacobson et al 1996). Using standard
neuropsychological tests we described visuo-spatial deficiencies in this group with problems
judging depth and movement, with simultaneous perception, with face recognition and with
orientation. Other groups described similar findings; among them Dutton et al. 1996.
Nystagmus, eye motility disorders, strabismus in children with WMDI
Nystagmus was previously reported to be absent in children with cerebral visual impairment.
In fact, the presence or absence of nystagmus was thought to reveal whether the cause of
visual impairment in a child was of ocular or cerebral origin. In the 1990ies we studied
fixation with infrared technique in a group of prematurely born children with cerebral visual
impairment due to WMDI and reported latent or manifest nystagmus in a majority of these
children (Jacobson et al. 1998). However, children with the most severe WMDI, with cerebral
palsy and visual impairment presented an ocular motor apraxia with complete disruption of
ocular motor organization, including absence of fixation and they had no nystagmus. Children
with less extensive WMDI, representing the other end of the clinical spectrum, all exhibited
nystagmus. Thus, nystagmus may be seen in children with cerebral visual impairment and the
presence of nystagmus may depend on the extent, and maybe, on the timing of the insult
which may affect input to the visual integrating circuits.
Defective smooth pursuit movements and inability to perform visually guided saccadic
movements in children with WMDI were found by us and by Cioni et al (1997) and Lanzi et
al (1998). Strabismus as a consequence of WMDI was reported by Scher et al (1989) and also
by us. The frequent finding of early-onset strabismus associated to WMDI may be the
consequence of a deficient afferent pathway caused by axonal interruption in the optic
Optic disc appearance in children with WMDI
Brodsky and Glasier (1993) found a link between optic nerve hypoplasia and WMDI, but did
not confirm their observations by fundus photography. We performed digital analysis of the
fundus photographs of children with WMDI and found that the time at which the primary
lesion of the optic radiation occurred was of importance for the appearance of the optic disc
(Jacobson et al. 1997, Jacobson et al. 2003). Early WMDI, sometimes of prenatal origin,
before gestational week 28 was associated with small discs. Normal-sized optic discs with
large cupping and consequently a reduced neuro-retinal rim area was the consequence of later
lesions, occurring after 28 weeks of gestation. In this developmental phase, the supportive
structures of the optic nerve have become established and probably do not adapt to the smaller
number of nerve fibers. The reduced rim area, either expressed as a small disc or as a large
cup in a normal-sized disc is probably the result of retrograde trans-synaptic degeneration of
optic nerve axons caused by the primary bilateral lesions in the optic radiation. Thus, optic
disc appearance together with the pattern of cerebral morphology depicted by MRI may give
information about the timing of the lesion.
Visual field defects in children with WMDI
Interruption of axons in the optic radiation may explain restriction of visual field (VF).
Variable restriction of the fields may also be attributable to problems with simultaneous
attention. Thus the functional VF may vary depending on the amount of visual stimuli present
and on the degree of attention paid to the fixation target. We assessed VF function in a group
of children with WMDI (Jacobson et al. 2006). All subjects had subnormal VF function,
although the depth and extension of the defects differed between subjects. The lower VF was
often more affected than the upper, which could be interpreted as a bilateral homonymous
lower quadrant dysopia due to the bilateral lesions in the upper part of the optic radiation. The
VF abnormalities could be demonstrated by both manual and computerized perimetry.
This case illustrates visual outcome associated to WMDI (Jacobson & Dutton 2000). A boy
was born prematurely at 32 full gestational weeks, with asphyxia at birth and he was early
diagnosed with cerebral palsy (spastic diplegia). His verbal development was normal.Visual
function is characterized by normal visual acuity (RE=LE 1.0) inferior altitudinal visual field
defects (Fig. 1), strabismus, nystagmus, defect saccades and smooth pursuit movements and
severe dorsal and ventral stream dysfunction. Thus, he is not able to judge depth by vision, he
cannot find his way around and he cannot recognise even family members if he meets them
unexpectedly. He is a slow reader, and often gets lost in the text. He has developed a battery
of compensating strategies based on hearing, tactile information and memory.
The optic discs are of normal size with large cupping (Fig. 2); the intraocular pressure is
normal. GDx of the fundus (Fig. 3) documents loss of ganglion cell axons above the optic disc
secondary to the brain lesions. MRI of the brain (Fig. 4 and 5) illustrates bilateral
periventricular WMDI. With fiber tractography of the optic radiation (Fig. 6) connecting
fibres are only detectable in the lower part of optic radiation on both sides which corresponds
well with the finding of an inferior bilateral homonymous quadrant anopia.
Figure 1. Altitudinal inferior visual field defects (bilateral inferior homonymous quadrant
anopias) due to bilateral WMDI affecting the upper parts of the optic radiations.
Figure 2. Large cupping of normal-sized optic discs; a consequence of retrograde transsynaptic
degeneration from interruption of axons in the optic radiation occurring after 28
Figure 3. GDx fundus images illustrating loss of nerve fibres layer above the optic discs, due
to retrograde trans-synaptic degeneration from the lesions in the upper part of both optic
radiations, corresponding to the visual field defects
Figure 4. This MRI at the level of the
posterior horns and trigonum shows the
occipital horns to be dilated due to reduced
periventricular white matter volume and
consequent loss of axons in motor and
visual pathways. Note how cortex abuts the
ventricular wall giving trigonum of the
ventricles a slight irregular shape. Also
note increased signal in remaining white
matter adjacent to the frontal horns and
extending deep into white matter in both
frontal lobes. (Courtesy of Olof Flodmark,
Dept of Neuroradiology, Karolinska
Figure 5. This image is at a level just at
the top of the lateral ventricles. Increase
signal beyond the borders of the lateral
ventricles in the parietal and frontal lobes
represent gliosis in damaged white matter.
(Courtesy of Olof Flodmark, Dept of
Neuroradiology, Karolinska University
Figure 6. Fiber tractography of the optic radiation (OR). It is difficult to accurately track the
OR with tensor-based tracking. Here, instead tractography between LGN and primary visual
cortex is performed with probabilistic tractography in a crossing-fiber model. The results
show a normal periventricular extent of OR in a healthy volunteer (Left). In our case (Right)
connecting fibers are only detectable in the lower part of OR. The degree of connectivity is
also lower (i.e. lower probability that initiated fibers in LGN reach the target area in primary
visual cortex), and more so on his left than on his right .side. This finding corresponds well
with loss of nerve fibres in the upper part of the fundi and with an inferior bilateral
homonymous quadrant anopia. (Courtesy of Annika Kits and Finn Lennartsson, Dept of
Neuroradiology, Karolinska University Hospital)
Visual field outcome in children with unilateral cerebral palsy
The frequency of VF defects in different groups of children with cerebral palsy has been
estimated to 20-25%. However, in most studies only confrontation techniques have been used.
We have recently assessed VF function in a group of children with unilateral cerebral palsy
(CP) with confrontation technique and with Goldmann perimetry. The type and extension of
brain lesion was documented with cerebral imaging. 62% had subnormal VF function, and
the VFs were severely restricted in 21%. The underlying brain lesions were malformation,
WMDI and cortico-subcortical lesions. VF function could be correlated to the pattern of brain
damage in cortico-subcortical lesions and in extensive lesions due to malformation or WMDI.
Total homonymous hemianopia was common in the cortico-subcortical group but rarely
found in children with malformation or WMDI. Five children had malformation or WMDI
engaging parts of the brain that usually contain the posterior visual system, but they had
normal VF function.
Thus, the VF function may be preserved by plasticity of the immature brain in children with
malformation and WMDI. Severely restricted VF function was more often associated with
brain damage occurring later in the developing brain. All children with severely restricted
VFs were identified with confrontation technique. Goldmann perimetry was a suitable method
to identify also relative VF defects in this age group of children with unilateral CP (Jacobson
et al. 2010).
Visual impairment due to pre-and perinatal brain damage has become the most common cause
of visual disturbance among children in the Western world; a consequence of increased
survival of very immature and very sick infants. The resulting visual dysfunction depends on
localisation and extension of the lesion involving the visual brain, but also on at what stage of
maturity the brain was damaged. As there is considerable plasticity of the developing visual
system, the outcome may be difficult to predict by routine imaging of the brain.
Assessments of acuities, visual field function, fixation, eye motility and of cognitive visual
function constitute the basis for implementation of developmental programmes designed for
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Ovanstående är ett utdrag ur:
|Advances in Pediatric Ophthalmology Research. Gunnar Lennerstrand and Gustaf Öqvist Seimyr, Eds. The Sigvard & Marianne Bernadotte Research Foundation for Children Eye Care. Stockholm, 2010.
Utgiven med anledning av Stiftelsens 20-års jubileum.