occult or subclinical forms simulating what has traditionally been referred to as “motor nystagmus.” For example, isolated foveal hypoplasia is increasingly recognized as a hereditary “cause” of infantile nystagmus in individuals with normal ocular pigmentation.437 Mutations in the PAX6 homeobox gene have been identified in this condition, although other ocular malformations often coexist when this mutation is present.43,44

Many patients with this condition have undoubtedly been classified as having motor nystagmus. However, there is strong evidence to support the notion that the afferent visual pathways in some individuals with infantile nystagmus are clinically and electrophysiologically normal.34 Thus, in referring to individuals in whom no clinical or electrophysiological signs of afferent visual pathway dysfunction are found, we advocate the term idiopathic infantile nystagmus.

History and Physical Examination

Until recently, it was believed that individuals with primary visual disorders accounted for a minority of infantile nystagmus cases, and electrophysiological testing was not routinely performed. Early studies utilizing electroretinography (ERG) and the testing of routine and hemispheric visual evoked potentials (VEPs) have demonstrated anterior visual pathway (i.e., bilateral retina or optic nerve) abnormalities in over 90% of patients with infantile nystagmus.

Taking into account the ascertainment biases that exist in different ophthalmologic and neurologic practices, it is now thought that approximately 50% of patients with infantile nystagmus have infantile nystagmus in the absence of underlying sensory visual defects.279 The diagnosis of infantile nystagmus therefore necessitates a directed investigation with the goal of identifying any obvious structural opacity or occult retinal dysfunction. Notably, infantile nystagmus associated with bilateral congenital cataracts has been noted to improve or even disappear when the cataracts are removed, and clear vision is restored within 1 month of the onset of the nystagmus.590 The decision of whether to perform further electrophysiological studies in an individual patient is predicated on the degree of clinical suspicion that a primary sensory disorder is likely to be present.

Gelbart and Hoyt213 have emphasized that individuals with idiopathic infantile nystagmus have significantly better visual acuities (20/40 to 20/70) than those with primary visual disorders (usually 20/70 or below). This finding reflects the fact that normal visual sensory systems are conducive to better foveation strategies. Although patients with only infantile nystagmus usually have a positive family history of nystagmus that suggests either an X-linked or autosomal

dominant inheritance pattern,213,490,581 singleton cases are also seen. Nevertheless, the absence of a family history in a child who appears to have idiopathic infantile nystagmus combined with low vision or other signs or symptoms of neurological disease, and visual acuity lower than 20/40 should raise suspicion of an underlying visual system or neurological disorder.100,307

Although the clinical features and time of onset cannot be used to predict the presence or absence of an underlying visual sensory disorder, other aspects of the history and physical examination are highly suggestive of primary visual impairment associated with infantile nystagmus. It is toward the detection of afferent visual pathway disease that the remainder of the parent interview and patient examination is directed.

Relevant History

When evaluating an infant or child with infantile nystagmus for the first time, certain historical points suggest afferent visual pathway dysfunction at the retinal level. A directed history in the child with infantile nystagmus should include the following inquiries:

1. Is the child unusually light sensitive? Photophobia in a child with infantile nystagmus suggests the presence of a congenital retinal dystrophy (which may be present despite a grossly normal retinal appearance). Children with achromatopsia or blue cone monochromatism are the most photophobic.

2. Does the child see better in daytime or at night? A history of night blindness suggests the possibility of congenital stationary night blindness (CSNB) or a rod–cone dystrophy. Children who are debilitated in daylight but function better in dim illumination may have congenital achromatopsia.

3. Is there a family history of poor vision, nystagmus, hypopigmentation, or easy sunburning? A family history of cutaneous hypopigmentation suggests the diagnosis of oculocutaneous albinism. A family history of nystagmus in the absence of hypopigmentation is consistent with infantile nystagmus, isolated foveal hypoplasia, or congenital retinal dystrophy, but is rare in optic nerve hypoplasia.

Physical Examination

In infants with infantile nystagmus, the ability to generate vertical optokinetic responses should be examined. In infants with relatively good vision, targets on a vertically moving optokinetic drum elicits a vertical optokinetic nystagmus superimposed on the child’s ongoing horizontal nystagmus. When vision is poor, a vertical optokinetic response cannot be

elicited. Cogan106 pointed out the importance of eliciting vertical optokinetic nystagmus in prognosticating vision in the infant with infantile nystagmus. The ability of a child to follow vertical optokinetic targets can be used to identify children who will be “mainstreamed” and educable in regular schools from those with severe visual impairment and will probably require visual aids and special services. Because infants with underlying sensory deficits may have a superimposed delayed visual maturation within the first 6 months of life, it may be important to wait until this age before conferring a poor visual prognosis on the child on the basis of absent vertical optokinetic responses. Conversely, it remains possible that delayed visual maturation or subcortical visual impairment in the first one to 3 months of life may be the facilitating inciting sensory system event in some children with infantile nystagmus, who are later called “idiopathic.”

In older children with infantile nystagmus, examination of visual acuity involves a number of additional steps. Visual acuity must be checked at distance and at near, with both eyes open and with each eye covered. This examination should be performed without correcting the anomalous head position to determine the real-life acuity (and also to elicit the full degree of torticollis necessary to see small objects). To avoid inducing a latent nystagmus during monocular occlusion, most examiners place a +5.00 lens rather than an occluder to blur the nonexamined eye.189 Placement of a green “Worth Four Dot” lens while the child views a duochrome slide reportedly accomplishes this goal to a greater degree. If children are wearing base out prism in their glasses, visual acuity should be checked only binocularly because the prism can move the monocular visual image away from the null point and reduce the measured acuity. It is also important to examine the near vision with the child spontaneously holding the near card in his or her preferred position (often very close to the face), because the acuity at this distance represents the child’s real-life reading acuity. As mentioned earlier, near visual acuity often exceeds distance visual acuity, in part because of the damping effect of convergence. Although similar near and distance visual acuity in children has been attributed to functional changes in the visual system resulting from the nearly incessant retinal image motion blur that is produced during development,5,60,259 this assumption is dubious because children whose nystagmus damps at near experience the same retinal image motion.

The results of visual acuity examination must then be placed in proper perspective. Clinic visual acuity provides restricted assessment of how the child with infantile nystagmus functions under real-world circumstances, both because it can decrease on a moment-to-moment basis when the child is nervous and because it generally assesses only a single gaze point. Because anxiety can exacerbate infantile nystagmus, children with infantile nystagmus often see better outside than in the elevated psychological state of measuring visual

acuity. They may also show a higher visual acuity when a friendly female technician administers the test than when an imposing, white-coated, male physician does. Several studies have found that it is the associated anxiety and not increased attentional demand of acuity testing that augments the nystagmus.13,578

It is also important to recognize that the clinical appearance of the nystagmus may not give an accurate impression of what the child sees. Although the intensity of nystagmus is a function of amplitude times frequency, it is the amplitude and not the frequency that is appreciated clinically. Foveation time is the primary indicator of visual function, while amplitude and frequency are secondary measures that only sometimes march in lockstep with visual acuity. Thus, patients with a high-frequency nystagmus may have better visual acuity than others with low-frequency infantile nystagmus, simply because they have more total foveation time. Recently, Dell’Osso et al have developed a nystagmus acuity function (NAFX) that depends solely on foveation quality with the primary emphasis on foveation time.167 All other portions of the infantile nystagmus waveform are discarded by the function.

The next goal of the ocular examination in the child with infantile nystagmus is to rule out ocular structural abnormalities that may reduce vision and lead to infantile nystagmus. Signs of aniridia, congenital cataracts, corneal opacities, iris transillumination defects, and macular hypoplasia are sought. When signs of partial aniridia are accompanied by midface hypoplasia, mental retardation, and nonprogressive cerebellar ataxia, the diagnosis of Gillespie syndrome can be established.215,426,478 If these features are absent, an examination of the optic discs to look for optic disc anomalies (most notably optic nerve hypoplasia or atrophy) should be undertaken. When the optic nerves are normal in appearance, the possibility of an underlying congenital retinal dystrophy must be considered (Table 8.2). Most congenital retinal dystrophies are characterized by a grossly normal retinal appearance in the early stages (although a sedated examination using direct ophthalmoscopy reveals diffuse narrowing of the retinal arterioles, often accompanied by a subtle wrinkling of the internal limiting membrane over the macula).

When structural ocular abnormalities are absent in infantile nystagmus, the following four clinical signs of congenital retinal dystrophy should be sought (Table 8.3):

1. Severe photophobia in a child with infantile nystagmus is strongly suggestive of a congenital retinal dystrophy. (Children with optic nerve hypoplasia, dominant optic atrophy, or cortical visual loss may be mildly photophobic).308

2. Bilateral high myopia in a child with infantile nystagmus should lead the examiner to suspect a congenital retinal dystrophy.

3. The paradoxical pupillary response is suggestive of either CSNB or achromatopsia.49,203 The paradoxical pupillary