Chapter 6 Vision Loss
In children, the complaint of blurred vision or vision loss is often nonspecific and may be difficult to elicit. Although most causes of vision loss in children result from ocular problems, neurologic disorders may have vision loss as a characteristic and early-manifesting feature [Thompson and Kaufman, 2003]. The ability to determine the cause of vision loss frequently aids in the diagnosis of the underlying neurologic disorder, may help determine prognosis, and can be used to monitor treatment efficacy. A thorough understanding of the anatomy of the visual system, the normal stages of visual development in children, and the signs and symptoms of visual dysfunction in children can greatly aid clinicians in evaluating children with vision loss.
Visual Development
Of all the sensory systems, the visual system is perhaps the most immature at birth. It is structurally incapable of processing sensory stimuli to yield maximum visual acuity, and structural changes must occur in the first months of life if normal vision is to be achieved. Postnatal developmental reorganization of the retina takes place during the first several months of life, with intercellular connections forming between the photoreceptors and inner retinal cells [Daw, 1994; Dubowitz et al., 1983, 1986]. Myelination of the optic radiations through the temporal, parietal, and occipital lobes occurs in the first year of life [Barkovich et al., 1992]. The most dramatic structural reorganization occurs in the striate cortex, where cortical cells responsible for the first stages of visual processing require normal focused visual input to develop in the correct orientation and to achieve maximum visual acuity. As described by Hubel and Wiesel [1962], visual deprivation causes abnormal formation of the striate cortical cells and leads to amblyopia. For vision to develop normally, all of the anatomic components of the visual system must be properly formed during development. The sensory neurologic end organ for processing vision is the eye itself. The focusing components of the eye must be developing normally, with clear corneas, crystalline lenses, and optically transparent vitreous media. Properly focused light energy is converted to electrical signals in the photoreceptors that transmit this electrical information through a complex series of interactions through multiple layers of the retina to the ganglion cells, which send projections through the superficial layers of the retina to the optic nerve, finally synapsing in the lateral geniculate nucleus. At the level of the lateral geniculate nucleus, the first levels of cortical processing and organization take place. From the lateral geniculate nucleus, axons project along the optic radiations through the parietal and temporal lobes to synapse in the striate cortex of the occipital lobe. Visual processing occurs in multiple locations in the occipital and temporal lobes in areas labeled V1–V5 [Amedi et al., 2003]. Processing of information from these centers occurs in visual association cortical centers, linking vision with speech, cognition, and more complex, higher cortical functions. A structurally intact neurologic substrate must receive properly focused visual information consistently over the first several years of life if normal, maximal visual acuity is to be achieved [Boothe et al., 1985].
Assessment and Quantification of Visual Acuity
Vision Assessment in Infancy
Although fixation behavior allows the clinician to determine whether the infant can see, it does not quantify visual acuity. Two techniques have been devised for this purpose. They are used clinically and for research purposes, and have allowed estimation of visual acuity in visually immature infants [Droste et al., 1991; Fulton et al., 1981]. The visual-evoked potential is an electrophysiologic test in which visual stimuli are presented to an alert and focused infant, and the cortical response to the visual stimulus is measured in a repeatable and quantifiable fashion [Iinuma et al., 1997] (see Chapter 12). Typically, the infant is placed in front of a computer monitor at a close distance and presented with a visually interesting pattern. The pattern may be an alternating checkerboard, or horizontally or vertically aligned black and white stripes [McCulloch and Taylor, 1992; Sokol et al., 1983]. The size of the stripes or checkerboard is described as cycles per degree or cycles per centimeter, which can be correlated to standard methods of visual or decimal visual acuity. Large targets are initially used to confirm that a cortical signal is recorded by occipitally placed scalp electrodes. The stimulus pattern is then slowly decreased in size until a recordable response can no longer be elicited. The limit of visual acuity is estimated when there is no longer a recordable electrical response to a viewed visual stimulus. The prerequisite for successfully completing this test is a child who is awake and paying attention to the monitor. As a child who looks elsewhere will not give an appropriate response, the examination must be performed quickly by a trained tester who is skilled at attracting the attention of young infants and maintaining their fixation [Good, 2001; Iinuma et al., 1997].
A second test used to quantify visual acuity is the forced-choice preferential looking test (PLT) [Mayer and Fulton, 1985]. Instead of using a cortically recorded electrical response, visual stimuli are presented and the child’s ability to see is determined by the ability to move the eyes toward the visual stimulus. Vertically or horizontally aligned black and white stripes are presented to the child on a test card. One side of the card has the stimulus; the other side of the card has a homogeneous gray background (Figure 6-1A). The infant is directed toward the test card in an apparatus where other visual stimuli are blocked from the infant’s view. When given a choice between a pattern background and a homogeneous background, infants instinctively are interested in the pattern background and make an eye movement or saccade toward the black and white stripes. An observer who is watching through a peephole in the middle of the card records in a masked fashion whether he or she sees the infant make the saccade. When the observer reliably identifies the eye movements, the card is removed, and the procedure repeated with test cards using smaller stimuli to quantify visual acuity. Limitations of this test include the need for an infant who is not irritable, a trained observer, and the appropriate apparatus (see Figure 6-1B) [Lewis and Maurer, 1986].
Vision Assessment in Children
Once a child becomes verbal but is still preliterate, matching tests can be used to quantify visual acuity (Figure 6-2). In the past, the tumbling E has been used; the examiner asks the child to show the direction of the letter E as it is presented in numerous different positions. This test requires some visual spatial integration and visual spatial perception, which some children find difficult, and so may give falsely low estimates of visual acuity. These tests have been replaced by matching games such as HOTV cards and child recognition symbols or Lea symbols that ask a child to match test optotypes that are presented in progressively smaller sizes (see Figure 6-2). These tests have been validated and are consistent with Snellen visual acuity, which is the gold standard for measurement of visual acuity in children and adults. Snellen visual acuity can be recorded in numerous forms using notations such as 20/20, decimal notation, or “logmar” notation, a method of quantification that allows more useful statistical analysis when conducting studies of visual acuity in children and adults.
Assessment of Ocular Motility
Assessment of ocular motility allows the examiner to assess function of cranial nerves III, IV, and VI (see Chapters 2–4). Ductions and versions can be tested using brightly colored toys and objects. It is important to check the child binocularly first before patching the infant’s eye because patching may be distracting and preclude acquiring useful information. Alignment should be checked using the alternate cover test where fixation is maintained and the visual axis of each eye is occluded alternately. Refixation of the eyes during alternate occlusion may indicate the presence of strabismus such as esotropia, exotropia, or hypertropia (Figure 6-3).
Clinical Features Associated with Vision Loss
Because symptoms are inconsistently reported, clinicians must be familiar with the physical signs of unilateral vision loss. During the newborn’s physical examination, pediatricians must look for the presence of a red pupillary reflex in each eye. The presence of a white pupil is called leukocoria (i.e., white body), and it is associated with poorly developed vision in one or both affected eyes in the infant (Figure 6-4). The causes of leukocoria are variable, and at a minimum, the condition can cause loss of vision; in more serious situations, leukocoria can be associated with life-threatening conditions such as retinoblastoma. Poor vision in one eye from birth often leads to strabismus that is noticed by the caretaker. Nystagmus is common when there is decreased visual acuity in one or both eyes resulting from a structural anomaly or to a functional deficit preventing visual information from being transmitted from the eye to the cortex [Good, 2001; Hoyt and Fredrick, 1998; Jan and Freeman, 1998]. A vision screening examination failed because of decreased visual acuity in one eye is one of the most common reasons why children are referred to their pediatrician and ophthalmologist. In an infant, bilateral vision loss is manifested by strabismus or nystagmus and visual inattention with poor fixation after 2 months of age. Older children with mild vision loss are usually asymptomatic and their problems are not detected until vision is screened by their pediatrician or family practitioner. Children who have progressive loss of visual acuity exhibit behaviors such as sitting extremely close to the television, being disinterested in distant objects or activities, and having difficulty with tasks that require fine visual acuity.
Associated ocular features of vision loss are important to confirm. Infants with poor vision often develop nystagmus by 2 months of age. They are visually inattentive and do not fix and follow well by this age, and they frequently manifest strabismus or a “wandering eye.” Older children usually do not complain of vision problems but have strabismus. They often close one eye or squint the eye in different lighting conditions, rub their eyes frequently, and occasionally complain of double vision when strabismus occurs suddenly. Children with significant vision loss have disrupted circadian rhythms and disturbed sleep–wake cycles [Leger et al., 1999, 2002; Okawa et al., 1987; Palm et al., 1997]. Other associated neurologic symptoms include headache, nausea, and vomiting. Children with profound vision loss demonstrate stereotyped behaviors such as body rocking, rhythmic head movement, and gazing at their fingers or hands as they are moved rapidly in front of their eyes and face [Fazzi et al., 1999].
Vision Loss in Infants
Clinical Manifestations
Strabismus is another common complaint in children and infants who have poor visual acuity. Strabismus early in life is not rare. Up to 30 percent of infants manifest intermittent deviations in the first 2 months of life, with exotropia occurring more commonly than esotropia [Nixon et al., 1985]. The deviation is usually intermittent and decreases in frequency over the first few months of life. Any child who has a strabismus lasting longer than a few months should be assessed for an underlying ocular anomaly. Constant deviations require close follow-up and early evaluation, particularly when there is constant exodeviation. Whereas infantile esotropia is readily apparent to the parents and quite frightening for them, this condition usually is not associated with an underlying neurologic abnormality. In contrast, constant exotropia should alert the practitioner that an underlying neurologic abnormality exists. If a constant esotropia is not associated with a sixth nerve palsy, it is usually not associated with neurologic problems.
Infants with visual problems also often demonstrate behavioral mannerisms that help suggest the cause of the vision loss [Brown et al., 1997b; Good and Hoyt, 1989]. Children with retinal dysfunction from congenital dysfunction of the photoreceptors or from retinopathy of prematurity often press their eyes to generate some sort of photic stimulation [Sonksen and Dale, 2002]. Children with cortical visual impairment may demonstrate overlooking behavior, an eccentric fixation, to maximize visual function in the visual fields that are least damaged from the underlying cortical injury. Patients with achromatopsia or congenital glaucoma may be quite photosensitive and demonstrate behaviors to shield their eyes from the light to minimize the dysphoric sensation they receive from visual stimulation.
Differential Diagnosis of Vision Loss in Infants
Structural Anomalies
Retinopathy of prematurity
Retinopathy of prematurity remains a common cause of vision impairment in infants, causing blindness in more than 500 infants each year in the United States. Despite intensive efforts by neonatologists and ophthalmologists to screen and treat the early stages of retinopathy, the disease progresses in some children. These patients develop cicatricial changes in the retina leading to vision impairment [Pierce and Mukai, 1994]. Premature infants who do not develop retinopathy of prematurity are still at risk for cerebral vision impairment due to periventricular leukomalacia [Jacobson et al., 2009].
Congenital cataracts
The causes of congenital cataracts vary throughout the world [Merin and Crawford, 1971]. In developed countries, the most common cause is autosomal-dominant cataracts, for which there is a clear history of congenital cataracts affecting multiple generations. These cataracts usually involve both eyes, with characteristic morphologic features. Infectious cataracts are uncommon in developed countries but are a leading cause of blindness in developing nations [Bale and Murph, 1992]. Immunizations are effective in reducing the incidence of infectious cataracts, but other viral illnesses can cause cataracts, as can other malformations. Metabolic causes of cataracts include galactosemia, with which infants present with poor feeding and failure to thrive, and galactokinase deficiency, with which infants may be quite healthy. These two metabolic disorders can be distinguished by performing enzymatic assays of erythrocytes. Early detection and dietary treatment may prevent the neurologic sequelae of these disorders.
Most developed countries have programs to identify children at risk for cataracts, but screening occasionally fails, and the clinician should be aware of the oil droplet morphology of these refractive types of cataracts. Early recognition and treatment can prevent loss of vision and may result in reversal of early cataracts in patients with galactosemia. Often, cataracts are idiopathic, with no previous family history of cataracts. Other neurometabolic conditions, such as mitochondrial disorders, can be associated with cataracts. Frequently, these are not present at birth but evolve in the first few years [Marcel, 1998; Sher et al., 1979]. For this reason, children with a suspected neurometabolic disorder should be followed to determine whether cataracts develop.
Treatment involves prompt recognition, removal of visually significant cataracts, and visual rehabilitation with intraocular lens implantation, extended-wear soft contact lenses, or aphakic spectacles [Basti et al., 1996].
Corneal opacity
Corneal opacities usually are easily detected by pediatricians or parents at birth when a white spot, or leukoma, is detected within the cornea. These opacities are associated with other structural anomalies, such as microphthalmos, or small eye, and anterior segment dysgenesis, which may also be associated with glaucoma or birth trauma (Figure 6-5). These corneal opacities can cause significant vision impairment and are difficult to correct, because the success rate of corneal transplantation is poor in infants.
Embryologically, the cornea and crystalline lens originate from surface ectoderm, and the iris, uvea, and ciliary body arise from neural crest and mesenchymal cells, with all of the structures forming the anterior segment of the eye. When development is abnormal, the condition is called anterior segment dysgenesis, which can be associated with congenital corneal and lens opacities and with glaucoma, all of which can lead to permanent vision impairment in infants. Patients with anterior segment dysgenesis often have other associated dysmorphic features that indicate the presence of a syndrome or sequence that, if unrecognized, can lead to profound morbidity of the affected child. One example of a form of abnormal anterior segment development is the absence or profound hypoplasia of the iris, a condition known as aniridia. Aniridia is associated with abnormal retinal development leading to nystagmus and vision impairment. It may occur in isolation, or it may occur as a feature of a syndrome characterized by Wilms’ tumor, genitourinary abnormalities, and mental retardation (WAGR) that is associated with deletion on the short arm of chromosome 11 (11p13). Anterior segment anomalies involving the cornea, lens, and iris are known as Peters’ anomaly, and if the child also has mental retardation, the diagnosis of Peters’ syndrome is made. Dysgenesis of the iris and peripheral cornea causing glaucoma is called Rieger’s anomaly, and if associated dental, cardiac, and cerebellar abnormalities are present, the term Rieger’s syndrome is used. Collaboration with a medical geneticist is helpful in identifying other dysmorphic features and determining appropriate genetic testing. In developing countries, leading causes of blindness associated with corneal opacities are vitamin A deficiency and measles [Semba and Bloem, 2004].
Ocular coloboma
Coloboma, or absence of tissue, can affect vision profoundly. If the coloboma involves the iris but not deeper tissues, visual acuity can be normal (Figure 6-6). However, when the coloboma involves the central retina, macula, or the optic nerve, vision can be severely impaired [Apple et al., 1982]. Children with bilateral colobomata are at high risk for underlying neurologic problems [Chestler and France, 1988; Russell-Eggitt et al., 1990]. Any child with bilateral colobomata should be evaluated for chromosomal trisomies and the CHARGE association (i.e., coloboma, heart defects, atresia choanae, retardation of growth and development, genitourinary problems, and ear anomalies). Aicardi’s syndrome should be considered in any female with a seizure disorder and ocular colobomata (Figure 6-7). Patients with Aicardi’s syndrome have ectopic gray matter and other CNS malformations; the disorder is X-linked and lethal for males [Carney et al., 1993; Gloor et al., 1989]. Coloboma of the optic nerve can also be associated with underlying renal disease, known as the papillorenal syndrome; this diagnosis is made by genetic testing for mutations in the PAX6 gene [Alur et al., 2010].
Congenital glaucoma
Congenital glaucoma occurs when the aqueous drainage pathways of the iris form abnormally, leading to increasing intraocular pressure, corneal edema, and optic nerve injury. Most cases of congenital glaucoma are not associated with specific syndromes or underlying neurologic disorders. The exception is Sturge–Weber syndrome, in which vascular anomalies involving the eye lead to increased episcleral venous pressure and glaucoma (see Chapter 40). These patients typically have cerebrovascular malformations, epilepsy, and contralateral hemiplegia.
Retinal dysplasia
Structural anomalies of the retina not associated with retinopathy of prematurity can lead to significant vision impairment. These forms of retinal dysplasia are frequently associated with a variety of neurologic malformations. An example is Walker–Warburg syndrome, in which congenital retinal dysplasia is associated with cerebral structural abnormalities such as hydrocephalus, agyria, and occasionally encephalocele (see Chapters 22–27). Muscle–eye–brain disease is another example of neurologic and retinal dysplasia resulting from abnormal glial development due to defective glycosylation of α-dystroglycan. This results in profound CNS involvement and significant vision loss [Shenoy et al., 2010]. Norrie’s disease is an X-linked condition in which retinal dysplasia is associated with mental retardation and deafness. In this condition, a genetic defect in the gene product norrin leads to abnormal endothelial cell migration and proliferation [Mintz-Hittner et al., 1996].
Optic nerve hypoplasia
Failure of the optic nerves to form properly leads to a small dysfunctional optic nerve [Siatkowski et al., 1997]. In optic nerve hypoplasia, the nerve is small and its morphology abnormal (Figure 6-8). Frequently, there is a double-ring sign; the scleral canal of the optic nerve is present, but the optic nerve tissues comprise only a small portion of the canal, leading to two distinct rings. Children with optic nerve hypoplasia frequently present with nystagmus. Children with optic nerve hypoplasia may have de Morsier’s syndrome, or septo-optic dysplasia, characterized by midline structural defects of the CNS (e.g., absence of the septum pellucidum, agenesis of the corpus callosum) in addition to neuroendocrine dysfunction (see Chapter 97). All children with optic nerve hypoplasia should undergo neuroimaging, with particular attention to the septum pellucidum, corpus callosum, and pituitary body [Brodsky et al., 1990]. The presence of an ectopic bright spot places the child at higher risk for neuroendocrine dysfunction. Patients suspected of having septo-optic dysplasia should have their growth and endocrine status monitored closely [Siatkowski et al., 1997; Skarf and Hoyt, 1984]. The absence of cerebral developmental anomalies does not mean that endocrine abnormalities will not occur, and children require continued endocrinologic follow-up [Garcia-Filion, 2008a & b]. A child may have normal endocrine function early in life and later develop panhypopituitarism. There have been numerous cases of sudden death associated with septo-optic dysplasia, in which affected children develop a febrile illness that leads to rapid decompensation and death due to adrenal insufficiency [Brodsky et al., 1997]. This complication may occur in children who have or have not received corticosteroid therapy. Parents should be advised concerning these potential risks and treat all illnesses seriously.
The cause of optic nerve hypoplasia is unknown, although there have been numerous case reports of optic nerve hypoplasia occurring in infants exposed prenatally to quinine, LSD, alcohol, and antiepileptic drugs [Lambert et al., 1987]. The condition is usually seen in young mothers and first-born children. Some infants with optic nerve hypoplasia develop moderate visual function, and the clinician should be careful in prognosticating long-term visual function based on the appearance and size of the optic nerve.
Ocular or oculocutaneous albinism
Normal pigment formation is essential for normal ocular development and normal function of the retinal pigment epithelium [Brodsky et al., 1993]. Albinism may involve the eye and skin (oculocutaneous albinism), or only the eye (ocular albinism); both forms are associated with decreased visual acuity. Patients with oculocutaneous albinism are more severely affected, with visual acuity in the 20/200 range, whereas those with ocular albinism have acuity in the range of 20/60 to 20/80. Both conditions manifest with nystagmus early in life. The diagnosis of ocular albinism is made by documenting transillumination defects in the iris during slit-lamp examination. This test can be performed in infants, and it obviates the need for further evaluation. Patients with oculocutaneous albinism should be assessed for systemic disease such as Chediak–Higashi syndrome, which is associated with white blood cell dysfunction and recurrent infections, and Hermansky–Pudlak syndrome, which increases the risk for rheologic abnormalities and clotting disorders [Carden et al., 1998].
Leber’s congenital amaurosis
Leber’s congenital amaurosis is a disorder of the photoreceptors and the retinal pigment epithelium in which photoreceptor function is extinguished [Babel et al., 1989; Brecelj and Steirn-Kranjc, 1999; Fulton et al., 1981]. Infants present with large-amplitude, slow-frequency, roving nystagmus. They frequently begin to press on their eyes by 2–3 months of age [Lambert et al., 1997; Sullivan et al., 1994], and they may have a completely normal ophthalmoscopic examination with normal-appearing optic nerve and retina. The diagnosis is established by electroretinography [Weleber, 2002]. In this test, the electrical amplitude of the retina is measured using a contact lens placed on the eye that is stimulated by bright lights to elicit a cone response and dim lights to stimulate a rod response (Figure 6-9). In congenital amaurosis, both rod and cone responses are extinguished [al-Salem, 1997; Heher et al., 1992].
