Disorders of the Visual System

Both congenital and acquired visual impairments in children are often associated with neurological disorders. The most common visual disorders are uncorrected refractive errors, amblyopia, strabismus, cataracts, and genetic disorders.

Assessment of Visual Acuity

The assessment of visual acuity in preverbal children relies mainly on assessing fixation and tracking as the infant or young child interacts with the environment.

Clinical Assessment

The pupillary light reflex is a test of the functional integrity of the subcortical afferent and efferent pathways and is reliably present after 31 weeks, gestation. A blink response to light develops at about the same time, and the lid may remain closed for as long as light is present (the dazzle reflex). The blink response to threat may not be present until 5 months of age. These responses are integrated in the brainstem and do not provide information on the cognitive (cortical) aspects of vision.

Observing fixation and following behavior is the principal means to assess visual function in newborns and infants. The human face, at a distance of approximately 30 cm, is the best target for fixation. Ninety percent of infants fixate on faces by 9 weeks of age. After obtaining fixation, the examiner slowly moves from side to side to test tracking . Visually directed grasping is present in normal children by 3 months of age but is difficult to test before 6 months of age. Absence of visually directed grasping may indicate a motor rather than a visual disturbance.

The refixation reflex evaluates the visual fields in infants and young children by moving an interesting stimulus in the peripheral field. Clues to visual impairment are structural abnormalities (e.g., microphthalmia, cloudy cornea), an absent or asymmetric pupillary response to light, dysconjugate gaze, nystagmus, and failure to fixate or track. Staring at a bright light source and oculodigital stimulation indicate severe visual impairment.

Visual Evoked Response

The visual evoked response to strobe light demonstrates the anatomical integrity of visual pathways without patient cooperation. At 30 weeks, gestation, a positive “cortical” wave with a peak latency of 300 ms is first demonstrable. The latency linearly declines at a rate of 10 ms each week throughout the last 10 weeks of gestation. In the newborn, the morphology of the visual evoked response is variable during wakefulness and active sleep and easiest to obtain just after the child goes to sleep. By 3 months of age, the morphology and latency of the visual evoked response are mature.

Congenital Blindness

Cortical blindness is the most common cause of congenital visual impairment among children referred to a neurologist. Ophthalmologists are more likely to see ocular abnormalities. The causes of congenital visual impairment are numerous and include prenatal and perinatal disturbances. Optic nerve hypoplasia, with or without other ocular malformations, is the most common ocular abnormality, followed by congenital cataracts and corneal opacities. Corneal abnormalities usually do not cause visual loss unless clouding is extensive. Such extensive clouding may develop in the mucopolysaccharidoses and Fabry disease. Box 16-1 lists conditions with corneal clouding present during childhood.

BOX 16-1

  • Cerebrohepatorenal syndrome (Zellweger syndrome)

  • Congenital syphilis

    Denotes the most common conditions and the ones with disease modifying treatments

  • Fabry disease (ceramide trihexosidosis)

  • Familial high-density lipoprotein deficiency (Tangier island disease)

  • Fetal alcohol syndrome

  • Glaucoma

  • Infantile GM 1 gangliosidosis

  • Juvenile metachromatic dystrophy

  • Marinesco-Sjögren disease

  • Mucolipidosis

  • Mucopolysaccharidoses

  • Multiple sulfatase deficiency

  • Pelizaeus-Merzbacher disease

  • Trauma (forceps at birth)

Corneal Clouding in Childhood

Congenital Cataract

For the purpose of this discussion, congenital cataract includes cataracts discovered within the first 3 months. Box 16-2 lists the differential diagnosis. Approximately one-third are hereditary, one-third syndromic, and one-third idiopathic.

BOX 16-2

Congenital Cataract

  • Chromosomal aberrations

    • Trisomy 13

    • Trisomy 18

    • Trisomy 21

      Cataracts may not be noted until infancy or childhood

    • Turner syndrome

  • Drug exposure during pregnancy

    • Chlorpromazine

    • Corticosteroids

    • Sulfonamides

  • Galactokinase deficiency

  • Galactose-1-phosphate uridyltransferase deficiency

  • Galactosemia

  • Genetic

    • Autosomal dominant inheritance

      • Hereditary spherocytosis

      • Incontinentia pigmenti

      • Marshall syndrome

      • Myotonic dystrophy

      • Schäfer syndrome

      • Without other anomalies

    • Autosomal recessive inheritance

      • Congenital ichthyosis

      • Congenital stippled epiphyses (Conradi disease)

      • Marinesco-Sjögren syndrome

      • Siemens syndrome

      • Smith-Lemli-Opitz syndrome

    • X-linked inheritance (oculocerebrorenal syndrome)

  • Idiopathic

    • Intrauterine infection

    • Mumps

    • Rubella

    • Syphilis

  • Maternal factors

    • Diabetes

    • Malnutrition

    • Radiation

    • Prematurity

  • Syndromes of uncertain etiology

    • Hallerman-Streiff syndrome

    • Pseudo-Turner syndrome

    • With oxycephaly

    • With polydactyly

Acquired Cataract

  • Drug-induced

    • Corticosteroids

    • Long-acting miotics

  • Genetic

    • Autosomal dominant inheritance (Alport syndrome)

    • Autosomal recessive inheritance

      • Cockayne disease

      • Hepatolenticular degeneration (Wilson disease)

      • Rothmund-Thompson syndrome

      • Werner syndrome

  • X-linked inheritance (pseudo-pseudohypoparathyroidism)

  • Chromosomal (Prader-Willi syndrome)

  • Metabolic

    • Cretinism

    • Hypocalcemia

    • Hypoparathyroidism

    • Juvenile diabetes

    • Pseudohypoparathyroidism

  • Trauma

  • Varicella (postnatal)

Dislocated Lens

  • Crouzon syndrome

  • Ehlers-Danlos syndrome

  • Homocystinuria

  • Hyperlysinemia

  • Marfan syndrome

  • Sturge-Weber syndrome

  • Sulfite oxidase deficiency

Cataract Etiology

In previous studies, intrauterine infection accounted for one-third of congenital cataracts. That percentage has declined with prevention of rubella embryopathy by immunization. Genetic and chromosomal disorders account for at least one-third, and the cause cannot be determined in half of the cases. Nonsyndromic, solitary, congenital cataracts are usually transmitted by autosomal dominant inheritance. The mode of transmission of syndromic congenital cataracts varies. In many hereditary syndromes, cataracts can be either congenital or delayed in appearance until infancy, childhood, or even adulthood. Several of these syndromes are associated with dermatoses: incontinentia pigmenti (irregular skin pigmentation), Marshall syndrome (anhidrotic ectodermal dysplasia), Schäfer syndrome (follicular hyperkeratosis), congenital ichthyosis, and Siemens syndrome (cutaneous atrophy).

Congenital cataracts occur in approximately 10 % of children with trisomy 13 and trisomy 18 and many children with trisomy 21. The association of congenital cataract and lactic acidosis or cardiomyopathy suggests a mitochondrial disorder.

Clinical Features

Small cataracts may impair vision and may be difficult to detect by direct ophthalmoscopy. Large cataracts appear as a white mass in the pupil and, if left in place, quickly cause deprivation amblyopia. The initial size of a cataract does not predict its course; congenital cataracts may remain stationary or increase in density but never improve spontaneously. Other congenital ocular abnormalities, aniridia, coloboma, and microphthalmos occur in 40–50 % of newborns with congenital cataracts.


Large cataracts are obvious on inspection. Smaller cataracts distort the normal red reflex when the direct ophthalmoscope is at arm’s length distance from the eye and a +12 to +20 lens is used.

Genetic disorders and maternal drug exposure are important considerations when cataracts are the only abnormality. Intrauterine disturbances, such as maternal illness and fetal infection, are usually associated with growth retardation and other malformations. Dysmorphic features are always an indication for ordering chromosome analysis. Galactosemia is suspected in children with hepatomegaly and milk intolerance (see Chapter 5 ), but cataracts may be present even before the development of systemic features.


Developmental amblyopia is preventable by recognizing and removing cataracts before age 3 months. Urgent referral to a pediatric ophthalmologist is the standard of care.

Congenital Optic Nerve Hypoplasia

Optic nerve hypoplasia is a developmental defect in the number of optic nerve fibers and may result from excessive regression of retinal ganglion cell axons. Hypoplasia may be bilateral or unilateral and varies in severity. It may occur as an isolated defect or be associated with intracranial anomalies. The most common association is with midline defects of the septum pellucidum and hypothalamus (septo-optic dysplasia). Septo-optic dysplasia ( DeMorsier syndrome ) is familial in some cases and transmitted as an autosomal recessive trait.

Clinical Features

The phenotype is highly variable; 62 % of affected children have isolated hypopituitarism and 30 % have the complete phenotype of pituitary hypoplasia, optic nerve hypoplasia, and agenesis of midline structures ( ). In one study group of 55 patients with optic nerve hypoplasia ( ), 49 % had an abnormal septum pellucidum on magnetic resonance imaging (MRI), and 64 % had a hypothalamic-pituitary axis abnormality. Twenty-seven patients (49 %) had endocrine dysfunction, and 23 of these had hypothalamic-pituitary axis abnormality. The frequency of endocrinopathy was higher in patients with an abnormal septum pellucidum (56 %) than a normal septum pellucidum (39 %) and the appearance of the septum pellucidum predicts the likely spectrum of endocrinopathy.

When hypoplasia is severe, the child is severely visually impaired and the eyes draw attention because of strabismus and nystagmus. Ophthalmoscopic examination reveals a small, pale nerve head ( Figure 16-1 ). A pigmented area surrounded by a yellowish mottled halo is sometimes present at the edge of the disk margin, giving the appearance of a double ring. The degree of hypothalamic-pituitary involvement varies. Possible symptoms include neonatal hypoglycemia and seizures, recurrent hypoglycemia in childhood, growth retardation, diabetes insipidus, and sexual infantilism. Some combination of mental retardation, cerebral palsy, and epilepsy is often present and indicates malformations in other portions of the brain.


Optic nerve hypoplasia. The optic nerve is small and pale, but the vessels are of normal size.


All infants with ophthalmoscopic evidence of optic nerve hypoplasia require cranial MRI and an assessment of endocrine status. The common findings on MRI are cavum septum pellucidum, hypoplasia of the cerebellum, aplasia of the corpus callosum, aplasia of the fornix, and an empty sella. Absence of the pituitary infundibulum with posterior pituitary ectopia indicates congenital hypopituitarism. Endocrine studies should include assays of growth hormone, antidiuretic hormone, and the integrity of hypothalamic-pituitary control of the thyroid, adrenal, and gonadal systems. Infants with hypoglycemia usually have growth hormone deficiency.

Superior segmental optic nerve hypoplasia is associated with congenital inferior visual field defects and occurs in children born to mothers with insulin-dependent diabetes.


No treatment is available for optic nerve hypoplasia, but endocrine abnormalities respond to replacement therapy. Children with corticotrophin deficiency may experience sudden death. Children with visual impairment may benefit from visual aids.


Coloboma is a defect in embryogenesis that may affect only the disk or may include the retina, iris, ciliary body, and choroid. Colobomas isolated to the nerve head appear as deep excavations, deeper inferiorly. They may be unilateral or bilateral. The causes of congenital coloboma are genetic (monogenic and chromosomal) and intrauterine disease (toxic and infectious). Retinochoroidal colobomas are glistening white or yellow defects inferior or inferior nasal to the disk. The margins are distinct and surrounded by pigment. Morning glory disk is not a form of coloboma; it is an enlarged dysplastic disk with a white excavated center surrounded by an elevated annulus of pigmentary change. Retinal vessels enter and leave at the margin of the disk, giving the appearance of a morning glory flower. The morning glory syndrome is associated with transsphenoidal encephaloceles. Affected children are dysmorphic with midline facial anomalies.

Acute Monocular or Binocular Blindness

The differential diagnoses of acute and progressive blindness show considerable overlap. Although older children recognize sudden visual loss, slowly progressive ocular disturbances may produce an asymptomatic decline until vision is severely disturbed, especially if unilateral. When finally noticed, the child’s loss of visual acuity seems acute. Teachers or parents are often the first to recognize a slowly progressive visual disturbance. Box 16-3 lists conditions in which visual acuity is normal and then suddenly lost. Box 16-4 lists disorders in which the underlying pathological process is progressive. The patient first perceives the condition. Therefore, consult both lists in the differential diagnosis of acute blindness. The duration of a transitory monocular visual loss suggests the underlying cause: seconds indicate optic disk disorders such as papilledema or drusen, minutes indicate emboli, hours indicate migraine, and days indicate optic neuropathy, most commonly optic neuritis.

BOX 16-3

  • Carotid dissection

    Denotes the most common conditions and the ones with disease modifying treatments

    (see Chapter 11 )

  • Cortical blindness

    • Anoxic encephalopathy (see Chapter 2 )

    • Benign occipital epilepsy (see Chapter 1 )

    • Hydrocephalus

    • Hypoglycemia

    • Hypertension (malignant or accelerated)

    • Hyperviscosity

    • Hypotension

    • Migraine (see Chapter 3 )

    • Occipital metastatic disease

    • Posttraumatic transient cerebral blindness

    • Systemic lupus erythematosus

    • Toxic (cyclosporine, etc.)

    • Trauma

  • Psychogenic blindness

    • Optic neuropathy

    • Demyelinating

  • Ischemic

  • Toxic

  • Traumatic

  • Pituitary apoplexy

  • Pseudotumor cerebri (see Chapter 4 )

  • Retinal disease

    • Central retinal artery occlusion

    • Migraine

    • Trauma

Causes of Acute Loss of Vision

BOX 16-4

Compressive Optic Neuropathies

Disorders of the Lens (see Box 16-3 )

  • Cataract

  • Dislocation of the lens

Hereditary Optic Atrophy

  • Leber hereditary optic neuropathy

  • Wolfram syndrome

Intraocular Tumors

Tapetoretinal Degenerations

  • Abnormal carbohydrate metabolism

    • Mucopolysaccharidosis (see Chapter 5 )

    • Primary hyperoxaluria

  • Abnormal lipid metabolism

  • Other syndromes of unknown etiology

    • Bardet-Biedl syndrome

    • Cockayne syndrome

    • Laurence-Moon syndrome

    • Refsum disease (see Chapter 7 )

    • Usher syndrome (see Chapter 17 )

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Mar 3, 2019 | Posted by in NEUROLOGY | Comments Off on Disorders of the Visual System
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